{ "uniprot_canonical_ac": "A4D1B5-1", "sequence": { "header": "sp|A4D1B5-1|GSAP_HUMAN Isoform 1 of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=2 CANONICAL=A4D1B5-1", "length": 854, "sequence": "MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYESLHVLNVERNGNIIYTYKDDKGNVVFGLYDCQTRQNELLYTFEKDLQVFSCSVNSERTLLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVKVLKAVDSYIWVQFLYPHIESHPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFVWAQWDMSEQRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDKFSKHLTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMTKGITFLNLDYYVAVYLPGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSGSLVLDCCSGKLYRALLSQSSLLQLLQNTCLDCEKMAALHCALYCGQGAQFLEAQIIQWISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHSSVLTWNTEIPGITLVTEDIALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEKTGKRRSAAYVRNILDNAVKVISNLEARNLGPRLTPLLQEEDSHQRLLMGLMVSELKDHFLRHLQGVEKKKIEQMVLDYISKLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTRILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDNTEKNEKLKFSIIVRLPPLIGQKICRLWDHPMSSNIISRNHVTRLLQNYKKQPRNSMINKSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFVEEAALKHTAMLLGL" }, "uniprot_id": "GSAP_HUMAN", "enzyme_annotation": [], "synonyms": { "protein": { "refseq": [ "gamma-secretase-activating protein isoform a", "protein pigeon homolog" ], "uniprotkb": [ "Gamma-secretase-activating protein", "GSAP", "Protein pigeon homolog" ] }, "gene": { "refseq": [ "GSAP", "PION" ], "uniprotkb": [ "GSAP", "PION" ] } }, "keywords": [], "species": [ { "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "id": "A4D1B5", "database": "UniProtKB" } ], "name": "Homo sapiens", "taxid": 9606 } ], "recommendedname": { "full": "Gamma-secretase-activating protein; GSAP; Protein pigeon homolog.", "short": "GSAP" }, "publication": [ { "title": "Frontal Cortex and Hippocampal gamma-Secretase Activating Protein Levels in Prodromal Alzheimer Disease.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/28743126", "journal": "Neuro-degenerative diseases", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Perez SE, Nadeem M, Malek-Ahmadi MH, He B, Mufson EJ", "date": "2017", "pmid": "28743126" }, { "title": "Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/26076991", "journal": "Scientific reports", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Chu J, Li JG, Hoffman NE, Stough AM, Madesh M, Pratico D", "date": "2015", "pmid": "26076991" }, { "title": "Common GSAP promoter variant contributes to Alzheimer's disease liability.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/25037285", "journal": "Neurobiology of aging", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Zhu M, Tao Y, He Q, Gao H, Song F, Sun YM, Li HL, Wu ZY, Saffen D", "date": "2014", "pmid": "25037285" }, { "title": "The role of gamma-secretase activating protein (GSAP) and imatinib in the regulation of gamma-secretase activity and amyloid-beta generation.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/23209290", "journal": "The Journal of biological chemistry", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Hussain I, Fabregue J, Anderes L, Ousson S, Borlat F, Eligert V, Berger S, Dimitrov M, Alattia JR, Fraering PC, Beher D", "date": "2013", "pmid": "23209290" }, { "title": "Immunohistochemical characterization of gamma-secretase activating protein expression in Alzheimer's disease brains.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/21718343", "journal": "Neuropathology and applied neurobiology", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Satoh J, Tabunoki H, Ishida T, Saito Y, Arima K", "date": "2012", "pmid": "21718343" }, { "title": "Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/20811458", "journal": "Nature", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" }, { "url": "https://www.uniprot.org/uniprot/A4D1B5/publications", "id": "A4D1B5", "database": "UniProtKB" } ], "authors": "He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Greengard P", "date": "2010", "pmid": "20811458" }, { "title": "Transcriptome analysis of human gastric cancer.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/16341674", "journal": "Mammalian genome : official journal of the International Mammalian Genome Society", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ], "authors": "Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS", "date": "2005", "pmid": "16341674" } ], "glycosylation": [], "mutation": [ { "start_pos": 305, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (2/5): patient freq. (2.0%); num. of cancers (3).", "sequence_org": "G", "disease": { "doid": "1612", "url": "http://disease-ontology.org/term/DOID:1612", "icd10": "", "name": "Breast cancer" }, "sequence_mut": "E", "subjects_tested": "50", "end_pos": 305, "type": "Point mutation" }, { "start_pos": 433, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (1/5): patient freq. (2.0%).", "sequence_org": "A", "disease": { "doid": "1612", "url": "http://disease-ontology.org/term/DOID:1612", "icd10": "", "name": "Breast cancer" }, "sequence_mut": "V", "subjects_tested": "50", "end_pos": 433, "type": "Point mutation" }, { "start_pos": 305, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "0.8", "annotation": "Filters passed (1/5): num. of cancers (3).", "sequence_org": "G", "disease": { "doid": "1781", "url": "http://disease-ontology.org/term/DOID:1781", "icd10": "", "name": "Thyroid cancer" }, "sequence_mut": "E", "subjects_tested": "129", "end_pos": 305, "type": "Point mutation" }, { "start_pos": 305, "subjects_positive": "2", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "0.8", "annotation": "Filters passed (1/5): num. of cancers (3).", "sequence_org": "G", "disease": { "doid": "9256", "url": "http://disease-ontology.org/term/DOID:9256", "icd10": "", "name": "Colorectal cancer" }, "sequence_mut": "E", "subjects_tested": "254", "end_pos": 305, "type": "Point mutation" }, { "start_pos": 183, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (1/5): patient freq. (2.0%).", "sequence_org": "H", "disease": { "doid": "1612", "url": "http://disease-ontology.org/term/DOID:1612", "icd10": "", "name": "Breast cancer" }, "sequence_mut": "R", "subjects_tested": "50", "end_pos": 183, "type": "Point mutation" }, { "start_pos": 604, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "1.1", "annotation": "Filters passed (1/5): patient freq. (1.1%). In dbSNP: rs570799989.", "sequence_org": "R", "disease": { "doid": "2394", "url": "http://disease-ontology.org/term/DOID:2394", "icd10": "", "name": "Ovarian cancer" }, "sequence_mut": "W", "subjects_tested": "93", "end_pos": 604, "type": "Point mutation" }, { "start_pos": 241, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (1/5): patient freq. (2.0%).", "sequence_org": "D", "disease": { "doid": "1781", "url": "http://disease-ontology.org/term/DOID:1781", "icd10": "", "name": "Thyroid cancer" }, "sequence_mut": "Y", "subjects_tested": "50", "end_pos": 241, "type": "Point mutation" }, { "start_pos": 439, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (1/5): patient freq. (2.0%).", "sequence_org": "G", "disease": { "doid": "1781", "url": "http://disease-ontology.org/term/DOID:1781", "icd10": "", "name": "Thyroid cancer" }, "sequence_mut": "D", "subjects_tested": "50", "end_pos": 439, "type": "Point mutation" }, { "start_pos": 71, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "2.0", "annotation": "Filters passed (1/5): patient freq. (2.0%).", "sequence_org": "G", "disease": { "doid": "1781", "url": "http://disease-ontology.org/term/DOID:1781", "icd10": "", "name": "Thyroid cancer" }, "sequence_mut": "*", "subjects_tested": "50", "end_pos": 71, "type": "Point mutation" }, { "start_pos": 653, "subjects_positive": "1", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/A4D1B5", "id": "A4D1B5", "database": "BioMuta" } ], "frequency": "1.5", "annotation": "Filters passed (1/5): patient freq. (1.5%).", "sequence_org": "W", "disease": { "doid": "1324", "url": "http://disease-ontology.org/term/DOID:1324", "icd10": "", "name": "Lung cancer" }, "sequence_mut": "L", "subjects_tested": "66", "end_pos": 653, "type": "Point mutation" } ], "isoforms": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5#A4D1B5-1", "isoform_ac": "A4D1B5-1", "locus": { "end_pos": 77311361, "start_pos": 77416321, "chromosome": "7", "evidence": [ { "url": "https://www.ensembl.org/id/ENST00000257626", "id": "ENST00000257626", "database": "Ensembl Transcript" }, { "url": "https://www.ensembl.org/id/ENSP00000257626", "id": "ENSP00000257626", "database": "Ensembl Peptide" } ] }, "sequence": { "header": "sp|A4D1B5-1|GSAP_HUMAN Isoform 1 of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=2 CANONICAL=A4D1B5-1", "length": 854, "sequence": "MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYESLHVLNVERNGNIIYTYKDDKGNVVFGLYDCQTRQNELLYTFEKDLQVFSCSVNSERTLLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVKVLKAVDSYIWVQFLYPHIESHPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFVWAQWDMSEQRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDKFSKHLTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMTKGITFLNLDYYVAVYLPGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSGSLVLDCCSGKLYRALLSQSSLLQLLQNTCLDCEKMAALHCALYCGQGAQFLEAQIIQWISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHSSVLTWNTEIPGITLVTEDIALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEKTGKRRSAAYVRNILDNAVKVISNLEARNLGPRLTPLLQEEDSHQRLLMGLMVSELKDHFLRHLQGVEKKKIEQMVLDYISKLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTRILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDNTEKNEKLKFSIIVRLPPLIGQKICRLWDHPMSSNIISRNHVTRLLQNYKKQPRNSMINKSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFVEEAALKHTAMLLGL" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#C9JRG7-1", "isoform_ac": "C9JRG7-1", "locus": { "end_pos": 77397027, "start_pos": 77406066, "chromosome": "7", "evidence": [ { "url": "https://www.ensembl.org/id/ENST00000430584", "id": "ENST00000430584", "database": "Ensembl Transcript" }, { "url": "https://www.ensembl.org/id/ENSP00000402748", "id": "ENSP00000402748", "database": "Ensembl Peptide" } ] }, "sequence": { "header": "tr|C9JRG7-1|GSAP_HUMAN Computationally mapped isoform of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=1 CANONICAL=A4D1B5-1", "length": 58, "sequence": "MLKEMEILFIPIRMIREMSSLDYMIVKPDKMSFYIPLRKTCKFSVALSTVKGLCLLQV" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#A4D1B5-2", "isoform_ac": "A4D1B5-2", "locus": { "end_pos": 0, "start_pos": 0, "chromosome": "", "evidence": [] }, "sequence": { "header": "sp|A4D1B5-2|GSAP_HUMAN Isoform 2 of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=2 CANONICAL=A4D1B5-1", "length": 577, "sequence": "MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYESLHVLNVERNGNIIYTYKDDKGNVVFGLYDCQTRQNELLYTFEKDLQVFSCSVNSERTLLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVKVLKAVDSYIWVQFLYPHIESHPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFVWAQWDMSEQRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDKFSKHLTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMTKGITFLNLDYYVAVYLPGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSGSLVLDCCSGKLYRALLSQSSLLQLLQNTCLDCEKMAALHCALYCGQGAQFLEAQWRQRADLNTNRVLSDFLKIIQWISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHSSVLTWNTEIPGITLVTEDIALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEV" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#H7C0Q7-1", "isoform_ac": "H7C0Q7-1", "locus": { "end_pos": 77314374, "start_pos": 77330367, "chromosome": "7", "evidence": [ { "url": "https://www.ensembl.org/id/ENST00000415112", "id": "ENST00000415112", "database": "Ensembl Transcript" }, { "url": "https://www.ensembl.org/id/ENSP00000396230", "id": "ENSP00000396230", "database": "Ensembl Peptide" } ] }, "sequence": { "header": "tr|H7C0Q7-1|GSAP_HUMAN Computationally mapped isoform of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=1 CANONICAL=A4D1B5-1", "length": 188, "sequence": "VLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEKTGKRRSAAYVRNILDNAVKVISNLEARNLGPRLTPLLQEEDSHQRLLMGLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTRILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLM" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#A4D1B5-3", "isoform_ac": "A4D1B5-3", "locus": { "end_pos": 0, "start_pos": 0, "chromosome": "", "evidence": [] }, "sequence": { "header": "sp|A4D1B5-3|GSAP_HUMAN Isoform 3 of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=2 CANONICAL=A4D1B5-1", "length": 559, "sequence": "MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYESLHVLNVERNGNIIYTYKDDKGNVVFGLYDCQTRQNELLYTFEKDLQVFSCSVNSERTLLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVKVLKAVDSYIWVQFLYPHIESHPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFVWAQWDMSEQRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDKFSKHLTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMTKGITFLNLDYYVAVYLPGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSGSLVLDCCSGKLYRALLSQSSLLQLLQNTCLDCEKMAALHCALYCGQGAQFLEAQIIQWISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHSSVLTWNTEIPGITLVTEDIALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEV" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#B7ZL33-1", "isoform_ac": "B7ZL33-1", "locus": { "end_pos": 77311361, "start_pos": 77320776, "chromosome": "7", "evidence": [ { "url": "https://www.ensembl.org/id/ENST00000441833", "id": "ENST00000441833", "database": "Ensembl Transcript" }, { "url": "https://www.ensembl.org/id/ENSP00000415402", "id": "ENSP00000415402", "database": "Ensembl Peptide" } ] }, "sequence": { "header": "tr|B7ZL33-1|GSAP_HUMAN Computationally mapped isoform of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=1 CANONICAL=A4D1B5-1", "length": 175, "sequence": "MTRILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDNTEKNEKLKFSIIVRLPPLIGQKICRLWDHPMSSNIISRNHVTRLLQNYKKQPRNSMINKSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFVEEAALKHTAMLLGL" } }, { "url": "https://www.uniprot.org/uniprot/A4D1B5#A4D1B5-4", "isoform_ac": "A4D1B5-4", "locus": { "end_pos": 0, "start_pos": 0, "chromosome": "", "evidence": [] }, "sequence": { "header": "sp|A4D1B5-4|GSAP_HUMAN Isoform 4 of Gamma-secretase-activating protein OS=Homo sapiens OX=9606 GN=GSAP PE=1 SV=2 CANONICAL=A4D1B5-1", "length": 248, "sequence": "MGLMVSELKDHFLRHLQGVEKKKIEQMVLDYISKLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTRILEATNSLFLPLPPGFHTLHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDNTEKNEKLKFSIIVRLPPLIGQKICRLWDHPMSSNIISRNHVTRLLQNYKKQPRNSMINKSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFVEEAALKHTAMLLGL" } } ], "pathway": [ { "url": "https://www.genome.jp/dbget-bin/www_bget?hsa:54103", "resource": "KEGG Pathway", "id": "hsa:54103", "name": "" } ], "function": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5#function", "annotation": "Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5#function", "id": "A4D1B5", "database": "UniProtKB" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "These data demonstrate that GSAP proteins are differentially dysregulated in severe Alzheimer Disease, but only the full-length form was associated with cognitive test scores in Alzheimer Disease.", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "GSAP cleavage via caspase-3 is regulated and depend upon the availability of 5-Lipoxygenase in Alzheimer's disease. Publication Status: Online-Only", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "Its promoter variant contributes to Alzheimer's disease liability.", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "Gamma-secretase activating protein (GSAP) and imatinib have roles in the regulation of gamma-secretase activity and amyloid-beta generation", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "Aberrant regulation of gamma-secretase activating protein expression plays a key role in acceleration of gamma-cleavage of beta-secretase-cleaved C-terminal fragment of amyloid precursor protein and accumulation of Abeta in AD brains", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "annotation": "A gamma-secretase activating protein (GSAP) that selectively increases amyloid-beta production via interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment.", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" } ] } ], "orthologs": [ { "uniprot_canonical_ac": "Q3TCV3-1", "protein_name": "Gamma-secretase-activating protein; GSAP; Protein pigeon homolog.", "sequence": { "length": 858, "sequence": "MALRLVTHFDVLEDVLPSLLTQAATTDEGDRAGVLETTYGSLRVLNIERNGNIIYTYKDNKGNAVFGLYDCQTRQNEHLYTFEKDMQAVSCSVNSERTVLAASFIQYTTEGVKNDLQPGSKCLTLLVEIHPVNNVKVLKAVDSCVWVQFLYPQAESHLLPQNHLLLISEEKYIERFHIQITREDGDRVVIRNSSHLPRDRLAEDFVWAQWDLSEQRLYYIELKESRSILKCIQFRADESFNLMFEMPLDITLTGLRFKLVNFGYDYRQDREKLCNQPSLCIFTNHTGSLCMCYSPKSDSREEITYSVFYLHKGYRKIFTAAPGSADSQVTNGADSQVTDGIAFLNLGYFVAVYSPGHFLHLLNIQHPDLVCHSLFLTGNNKIAAVLPPSPLQSLPGSLVLDCYSGKVYRVTLDQSYLLRFLWNAHLDCERMAALHCILSCSQDPGFPEEQIIQWISEHVSACHSFDLIQEFLIASSYWSVYAELDDMGMLLQYSSVLTWNTEIPGIKFTTEELPLPLMKVYGLKGYWAKLNSNLEYIKYTKPHLHYHNSVVRREWHNLISEERTGKRRSTMYVRNILENAMKVIASMETRTLEPRLIPFLQEEDRHQRLLMGLMVSELRDHLLRHLQGVEKKKIEQMVLDYISKLLDLIWCLLETSWRKHSMHPLVLHLNSHCSAADFEVFHLMTRILDAASSLCLPLPPGFHSLHTILGVHCLPLYSLLHYIDNGVLLLTETAVTRLMKDLDNSEKNEQLKFSIIVRLPPLIGQKVCRLWDHPMSSNIISRNHVARLLKNYRKEPRNSMIDKSSFPVEFLPLNYFIEILMGLESSNQALYGFEGHDNVDAEFVEEAALKHTTMLLGL" }, "evidence": [ { "url": "https://omabrowser.org/oma/group/A4D1B5/", "id": "A4D1B5", "database": "OMA" }, { "url": "http://www.informatics.jax.org/homology/45504", "id": "45504", "database": "MGI" } ], "organism": "Mus musculus", "tax_id": 10090 }, { "uniprot_canonical_ac": "A0A0G2JWZ3-1", "protein_name": "Similar to RIKEN cDNA A530088I07; Gamma-secretase-activating protein.", "sequence": { "length": 846, "sequence": "MALRLVTHFDVLADVLPSLLVQAATADEGDEGAETTLGSLRVLNIERNGDIIYTYKDNKGNAVFGIFDCQTRENEHLYTFEKDMQAVSCSVNSERTVLAASFIQYTEGVRSELQPGSKCLTLLVEIHPVNNVTVLKAVDSCVWVQFLYPQAESHLLAQNHLLLISEEKYIERFHIQITREDGNRVVIRNSSHLPRERIAEDFVWAQWDVSEQRIHYIELQESRSILKCVQFWADESFTIMFEMPLDISLSGLRFKLVNFGYDYRQDQAKLCHQPSLCIFTNHTGSLCVCYSPKSDSWKEITYSVFYLHKGYRKTFTVAPGSTDSQVANGVTFLNLGYFVAVYSPCRFLHLLNIRHPDLICHSLFLTGNNKTAAVLPPSPLQSLPGSLILDCSSGKVYRATLDQSYLMGFLWNAQLDCEKMAALHCALSCDSDPGFPEQIVQWVSERVSACHSFDLIQEFLIASSYWSVYPGLDDVDLLLPYSSVLTWDTEIPGMKLVTEELPLPLMKVYSLKGYWAKLNSNLEYIKYTKPHLHYHNSVVRREWHNLISEERTGKRRSTMYVRNILDNAVKVISNMEMKTFEPRLIPLLQEEDRHQRLLMGLMVSELRDHLLRHLQGVEKKKIEQMVLDYISKLLDLVWCLLETSWRKHSVHPWVLHLNEHGSPADFEVFHLMTRILDAASSLCFPLPPGFHSLHTILGVHCLPLYNLLHYIDNGVLLLTETVVTRLMKDLDNSEKNEKLKFSIIVRLPPLIGQKVCRLWDHPMSSNIISRNHVAQLLKNYKKEPQSSMIDKSSFPVEFLPLNYFIEILMHLESSNQALHGFEGHDNVDAEFVEEAALKHTTSLLGL" }, "evidence": [ { "url": "https://omabrowser.org/oma/group/A4D1B5/", "id": "A4D1B5", "database": "OMA" }, { "url": "http://www.informatics.jax.org/homology/45504", "id": "45504", "database": "MGI" } ], "organism": "Rattus norvegicus", "tax_id": 10116 } ], "refseq": { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "ac": "NP_059135.2", "name": "gamma-secretase-activating protein isoform a; protein pigeon homolog.", "summary": "Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]." }, "go_annotation": { "categories": [ { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0001540", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "id": "A4D1B5", "database": "UniProtKB" } ], "name": "amyloid-beta binding", "id": "GO:0001540" } ], "total": 1, "name": "Molecular Function" }, { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005802", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "id": "A4D1B5", "database": "UniProtKB" } ], "name": "trans-Golgi network", "id": "GO:0005802" } ], "total": 1, "name": "Cellular Component" }, { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:1902004", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "id": "A4D1B5", "database": "UniProtKB" } ], "name": "positive regulation of amyloid-beta formation", "id": "GO:1902004" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030162", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "id": "A4D1B5", "database": "UniProtKB" } ], "name": "regulation of proteolysis", "id": "GO:0030162" } ], "total": 2, "name": "Biological Process" } ] }, "site_annotation": [ { "end_pos": 290, "annotation": "n_glycosylation_sequon", "start_pos": 288 }, { "end_pos": 456, "annotation": "n_glycosylation_sequon", "start_pos": 454 }, { "end_pos": 545, "annotation": "n_glycosylation_sequon", "start_pos": 543 }, { "end_pos": 800, "annotation": "n_glycosylation_sequon", "start_pos": 798 } ], "crossref": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_059135.2", "id": "NP_059135.2", "database": "RefSeq" }, { "url": "https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=28042", "id": "28042", "database": "HGNC" }, { "url": "https://pharos.nih.gov/targets/A4D1B5", "id": "A4D1B5", "database": "PHAROS" }, { "url": "https://www.nextprot.org/entry/NX_A4D1B5", "id": "NX_A4D1B5", "database": "neXtProt" }, { "url": "http://www.genecards.org/cgi-bin/carddisp.pl?gene=GSAP", "id": "GSAP", "database": "GeneCards" }, { "url": "https://www.genome.jp/dbget-bin/www_bget?hsa:54103", "id": "hsa:54103", "database": "KEGG Pathway" }, { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" }, { "url": "https://omabrowser.org/oma/group/HEPCCHI/", "id": "HEPCCHI", "database": "OMA" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR026172", "id": "IPR026172", "database": "InterPro" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR028010", "id": "IPR028010", "database": "InterPro" }, { "url": "http://pfam.xfam.org/family/PF14959", "id": "PF14959", "database": "Pfam" }, { "url": "http://www.pantherdb.org/panther/family.do?clsAccession=PTHR13630", "id": "PTHR13630", "database": "PANTHER" }, { "url": "http://research.bioinformatics.udel.edu/pro/entry/PR_A4D1B5", "id": "PR_A4D1B5", "database": "PRO" }, { "url": "https://www.ebi.ac.uk/intact/interactors/id:A4D1B5*", "id": "A4D1B5", "database": "IntAct" }, { "url": "https://www.ncbi.nlm.nih.gov/gene/54103", "id": "54103", "database": "GeneID" } ], "expression_disease": [ { "trend": "Down", "disease": { "doid": "11054", "url": "http://disease-ontology.org/term/DOID:11054", "icd10": "", "name": "DOID:11054 / Urinary bladder cancer [UBC]" }, "significant": "No", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Down", "disease": { "doid": "3571", "url": "http://disease-ontology.org/term/DOID:3571", "icd10": "", "name": "DOID:3571 / Liver cancer [Livca]" }, "significant": "No", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Down", "disease": { "doid": "3907", "url": "http://disease-ontology.org/term/DOID:3907", "icd10": "", "name": "DOID:3907 / Lung squamous cell carcinoma" }, "significant": "Yes", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Up", "disease": { "doid": "10283", "url": "http://disease-ontology.org/term/DOID:10283", "icd10": "", "name": "DOID:10283 / Prostate cancer [PCa]" }, "significant": "Yes", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Down", "disease": { "doid": "1781", "url": "http://disease-ontology.org/term/DOID:1781", "icd10": "", "name": "DOID:1781 / Thyroid cancer [Thyca]" }, "significant": "Yes", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Down", "disease": { "doid": "5041", "url": "http://disease-ontology.org/term/DOID:5041", "icd10": "", "name": "DOID:5041 / Esophageal cancer [EC]" }, "significant": "No", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] }, { "trend": "Down", "disease": { "doid": "3910", "url": "http://disease-ontology.org/term/DOID:3910", "icd10": "", "name": "DOID:3910 / Lung adenocarcinoma" }, "significant": "No", "evidence": [ { "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/A4D1B5", "id": "A4D1B5", "database": "BioXpress" } ] } ], "uniprot_ac": "A4D1B5", "disease": [], "mass": { "monoisotopic_mass": 97802.0, "chemical_mass": 97802.0 }, "expression_tissue": [ { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0009853", "uberon": "0009853", "name": "Body of uterus" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000458", "uberon": "0000458", "name": "Endocervix" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000948", "uberon": "0000948", "name": "Heart" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000473", "uberon": "0000473", "name": "Testis" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0002369", "uberon": "0002369", "name": "Adrenal gland" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000992", "uberon": "0000992", "name": "Ovary" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000996", "uberon": "0000996", "name": "Vagina" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001155", "uberon": "0001155", "name": "Colon" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001987", "uberon": "0001987", "name": "Placenta" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000955", "uberon": "0000955", "name": "Brain" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001160", "uberon": "0001160", "name": "Fundus of stomach" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001150", "uberon": "0001150", "name": "Body of pancreas" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0002048", "uberon": "0002048", "name": "Lung" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000007", "uberon": "0000007", "name": "Pituitary gland" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0002107", "uberon": "0002107", "name": "Liver" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0002046", "uberon": "0002046", "name": "Thyroid gland" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0000178", "uberon": "0000178", "name": "Blood" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001043", "uberon": "0001043", "name": "Esophagus" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0002367", "uberon": "0002367", "name": "Prostate gland" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001161", "uberon": "0001161", "name": "Body of stomach" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] }, { "tissue": { "url": "http://purl.obolibrary.org/obo/UBERON_0001255", "uberon": "0001255", "name": "Urinary bladder" }, "present": "yes", "evidence": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSG00000186088", "id": "ENSG00000186088", "database": "Bgee" } ] } ], "gene": [ { "url": "https://www.uniprot.org/uniprot/A4D1B5", "name": "GSAP; PION.", "locus": { "end_pos": 77310751, "start_pos": 77416400, "chromosome": "7", "evidence": [ { "url": "https://www.ensembl.org/id/ENSG00000186088", "id": "ENSG00000186088", "database": "Ensembl Gene" } ] } } ] }