{ "uniprot_canonical_ac": "P01137-1", "uniprot_ac": "P01137", "uniprot_id": "TGFB1_HUMAN", "mass": { "chemical_mass": 44325.0, "monoisotopic_mass": 44325.0 }, "refseq": { "ac": "NP_000651", "name": "transforming growth factor beta-1 proprotein preproprotein", "summary": "This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016].", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651" }, "gene_names": [ { "name": "TGFB1", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/P01137", "id": "P01137" }, { "name": "CED; DPD1; IBDIMDE; LAP; TGF-beta1; TGFB; TGFbeta", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651", "id": "NP_000651" }, { "name": "TGFB1", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651", "id": "NP_000651" }, { "name": "TGFB", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/P01137", "id": "P01137" } ], "protein_names": [ { "name": "Transforming growth factor beta-1 proprotein", "resource": "UniProtKB", "type": "recommended", "url": "", "id": "P01137" }, { "name": "prepro-transforming growth factor beta-1; latency-associated peptide; TGF-beta-1; transforming growth factor beta-1 proprotein; transforming growth factor beta1", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651", "id": "NP_000651" }, { "name": "transforming growth factor beta-1 proprotein preproprotein", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651", "id": "NP_000651" } ], "function": [ { "annotation": "Association between single nucleotide polymorphisms, TGF-beta1 promoter methylation, and polycystic ovary syndrome. Publication Status: Online-Only", "evidence": [ { "database": "RefSeq", "id": "NP_000651", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651" }, { "database": "PubMed", "id": "38166771", "url": "https://glygen.org/publication/PubMed/38166771" } ] }, { "annotation": "Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653, PubMed:30696809). Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292, PubMed:30696809).", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137#function" }, { "database": "PubMed", "id": "25310401", "url": "https://glygen.org/publication/PubMed/25310401" }, { "database": "UniProtKB", "id": "P04202", "url": "https://www.uniprot.org/uniprot/P04202#function" }, { "database": "PubMed", "id": "25893292", "url": "https://glygen.org/publication/PubMed/25893292" }, { "database": "PubMed", "id": "20207738", "url": "https://glygen.org/publication/PubMed/20207738" }, { "database": "PubMed", "id": "22278742", "url": "https://glygen.org/publication/PubMed/22278742" }, { "database": "PubMed", "id": "8939931", "url": "https://glygen.org/publication/PubMed/8939931" }, { "database": "PubMed", "id": "19750484", "url": "https://glygen.org/publication/PubMed/19750484" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" }, { "database": "PubMed", "id": "8617200", "url": "https://glygen.org/publication/PubMed/8617200" }, { "database": "PubMed", "id": "29109152", "url": "https://glygen.org/publication/PubMed/29109152" }, { "database": "PubMed", "id": "2022183", "url": "https://glygen.org/publication/PubMed/2022183" }, { "database": "PubMed", "id": "19651619", "url": "https://glygen.org/publication/PubMed/19651619" }, { "database": "PubMed", "id": "30696809", "url": "https://glygen.org/publication/PubMed/30696809" }, { "database": "PubMed", "id": "29483653", "url": "https://glygen.org/publication/PubMed/29483653" } ] }, { "annotation": "Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447).", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137#function" }, { "database": "PubMed", "id": "22278742", "url": "https://glygen.org/publication/PubMed/22278742" }, { "database": "PubMed", "id": "29909984", "url": "https://glygen.org/publication/PubMed/29909984" }, { "database": "PubMed", "id": "8939931", "url": "https://glygen.org/publication/PubMed/8939931" }, { "database": "PubMed", "id": "19750484", "url": "https://glygen.org/publication/PubMed/19750484" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" }, { "database": "PubMed", "id": "8617200", "url": "https://glygen.org/publication/PubMed/8617200" }, { "database": "PubMed", "id": "2022183", "url": "https://glygen.org/publication/PubMed/2022183" }, { "database": "PubMed", "id": "19651619", "url": "https://glygen.org/publication/PubMed/19651619" } ] }, { "annotation": "TGFbeta1 induces CXCL1 to promote stemness features in lung cancer.", "evidence": [ { "database": "RefSeq", "id": "NP_000651", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651" }, { "database": "PubMed", "id": "38158808", "url": "https://glygen.org/publication/PubMed/38158808" } ] }, { "annotation": "This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016].", "evidence": [ { "database": "RefSeq", "id": "NP_000651", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_000651" } ] }, { "annotation": "Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.", "evidence": [ { "database": "UniProtKB", "id": "A0A7I2YQL8", "url": "https://www.uniprot.org/uniprot/A0A7I2YQL8#function" }, { "database": "UniProtKB", "id": "ARBA00002007", "url": "https://www.uniprot.org/uniprot/ARBA00002007#function" }, { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137#function" }, { "database": "PubMed", "id": "29109152", "url": "https://glygen.org/publication/PubMed/29109152" }, { "database": "PubMed", "id": "27252363", "url": "https://glygen.org/publication/PubMed/27252363" }, { "database": "UniProtKB", "id": "A0A499FJK2", "url": "https://www.uniprot.org/uniprot/A0A499FJK2#function" } ] } ], "disease": [ { "disease_id": "DOID:4997", "recommended_name": { "id": "DOID:4997", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4997", "name": "Camurati-Engelmann disease", "description": "An osteosclerosis that has_material_basis_in mutations in the TGFB1 gene which results_in increased bone density located_in long bone." }, "synonyms": [ { "id": "DOID:4997", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4997", "name": "Diaphyseal dysplasia", "description": "" }, { "id": "DOID:4997", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4997", "name": "Engelman's disease", "description": "" }, { "id": "DOID:4997", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4997", "name": "progressive diaphyseal dysplasia", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Camurati-Engelmann disease", "description": "Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability." }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Camurati-Engelmann disease", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Camurati-Engelmann syndrome", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Camurati-Englemann disease", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Engelman's disease", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "diaphyseal dysplasia", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "progressive diaphyseal dysplasia", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "CAEND", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "CED", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "DPD1", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "Engelmann disease", "description": "" }, { "id": "MONDO:0007542", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007542", "name": "diaphyseal dysplasia 1, progressive", "description": "" }, { "id": "MONDO:0011690", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0011690", "name": "Camurati-Engelmann disease, type 2", "description": "Camurati-Engelmann Disease not associated with TGFB1. This is an n-of-1 use case where only one patient or family has been described with this disorder." }, { "id": "MONDO:0011690", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0011690", "name": "Camurati-Engelmann disease, type 2", "description": "" }, { "id": "MONDO:0011690", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0011690", "name": "CAEND2", "description": "" }, { "id": "MONDO:0011690", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0011690", "name": "Camurati Engelmann disease, type 2", "description": "" }, { "id": "MONDO:0011690", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0011690", "name": "progressive diaphyseal dysplasia with striations of the bones", "description": "" }, { "id": "MIM:131300", "resource": "MIM", "url": "https://www.omim.org/entry/131300", "name": "Camurati-Engelmann disease", "description": "Camurati-Engelmann disease" } ], "evidence": [ { "id": "131300", "database": "MIM", "url": "https://www.omim.org/entry/131300" } ] }, { "disease_id": "MONDO:0032601", "recommended_name": { "id": "MONDO:0032601", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0032601", "name": "inflammatory bowel disease, immunodeficiency, and encephalopathy", "description": "" }, "synonyms": [ { "id": "MONDO:0032601", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0032601", "name": "IBDIMDE", "description": "" }, { "id": "MONDO:0032601", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0032601", "name": "INFLAMMATORY BOWEL DISEASE, IMMUNODEFICIENCY, AND ENCEPHALOPATHY", "description": "" }, { "id": "MIM:618213", "resource": "MIM", "url": "https://www.omim.org/entry/618213", "name": "Inflammatory bowel disease, immunodeficiency, and encephalopathy", "description": "Inflammatory bowel disease, immunodeficiency, and encephalopathy" } ], "evidence": [ { "id": "618213", "database": "MIM", "url": "https://www.omim.org/entry/618213" } ] } ], "snv": [ { "evidence": [ { "id": "rs764002407", "database": "dbSNP", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs764002407" }, { "id": "rs764002407", "database": "ExAC", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs764002407" }, { "id": "rs764002407", "database": "gnomAD", "url": "http://gnomad.broadinstitute.org/awesome?query=rs764002407" } ], "glycoeffect": [ "n-glyco-sequon-loss" ], "start_pos": 136, "end_pos": 136, "sequence_org": "N", "sequence_mut": "Y", "comment": "Germline mutation passed 1 out of 1 filters: n-glyco-sequon-loss (NTS->YTS).", "chr_id": "19", "chr_pos": "41348405", "ref_nt": "A", "alt_nt": "null", "minor_allelic_frequency": "", "site_lbl": "N136", "keywords": [ "ebi", "germline" ] }, { "evidence": [ { "id": "rs780397214", "database": "dbSNP", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs780397214" }, { "id": "rs780397214", "database": "ExAC", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs780397214" }, { "id": "rs780397214", "database": "gnomAD", "url": "http://gnomad.broadinstitute.org/awesome?query=rs780397214" } ], "glycoeffect": [ "n-glyco-sequon-loss" ], "start_pos": 176, "end_pos": 176, "sequence_org": "N", "sequence_mut": "S", "comment": "Germline mutation passed 1 out of 1 filters: n-glyco-sequon-loss (NNS->SNS).", "chr_id": "19", "chr_pos": "41344854", "ref_nt": "C", "alt_nt": "null", "minor_allelic_frequency": "", "site_lbl": "N176", "keywords": [ "ebi", "germline" ] }, { "evidence": [ { "id": "rs1181694127", "database": "dbSNP", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs1181694127" }, { "id": "rs1181694127", "database": "gnomAD", "url": "http://gnomad.broadinstitute.org/awesome?query=rs1181694127" } ], "glycoeffect": [ "n-glyco-sequon-gain", "o-glyco-site-loss" ], "start_pos": 287, "end_pos": 287, "sequence_org": "S", "sequence_mut": "N", "comment": "Germline mutation passed 1 out of 1 filters: n-glyco-sequon-gain (SST->NST).", "chr_id": "19", "chr_pos": "41331139", "ref_nt": "T", "alt_nt": "null", "minor_allelic_frequency": "", "site_lbl": "S287", "keywords": [ "ebi", "germline" ] }, { "evidence": [ { "id": "rs943475580", "database": "dbSNP", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs943475580" }, { "id": "rs943475580", "database": "TOPMed", "url": "https://www.ncbi.nlm.nih.gov/snp/rs943475580#frequency_tab" }, { "id": "rs943475580", "database": "gnomAD", "url": "http://gnomad.broadinstitute.org/awesome?query=rs943475580" } ], "glycoeffect": [ "n-glyco-sequon-gain", "o-glyco-site-loss" ], "start_pos": 388, "end_pos": 388, "sequence_org": "K", "sequence_mut": "N", "comment": "Germline mutation passed 1 out of 1 filters: n-glyco-sequon-gain (KCS->NCS).", "chr_id": "19", "chr_pos": "41331061", "ref_nt": "A", "alt_nt": "null", "minor_allelic_frequency": "", "site_lbl": "K388", "keywords": [ "ebi", "germline" ] }, { "evidence": [ { "id": "rs1411294450", "database": "dbSNP", "url": "https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs&rs=rs1411294450" }, { "id": "rs1411294450", "database": "TOPMed", "url": "https://www.ncbi.nlm.nih.gov/snp/rs1411294450#frequency_tab" } ], "glycoeffect": [ "n-glyco-sequon-loss" ], "start_pos": 82, "end_pos": 82, "sequence_org": "N", "sequence_mut": "D", "comment": "Germline mutation passed 1 out of 1 filters: n-glyco-sequon-loss (NST->DST).", "chr_id": "19", "chr_pos": "41352801", "ref_nt": "C", "alt_nt": "null", "minor_allelic_frequency": "", "site_lbl": "N82", "keywords": [ "ebi", "germline" ] } ], "mutagenesis": [ { "start_pos": 158, "end_pos": 158, "sequence_org": "L", "sequence_mut": "A", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 160, "end_pos": 160, "sequence_org": "L", "sequence_mut": "A", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 160, "end_pos": 160, "sequence_org": "L", "sequence_mut": "R", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 193, "end_pos": 193, "sequence_org": "P", "sequence_mut": "A", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 193, "end_pos": 193, "sequence_org": "P", "sequence_mut": "R", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 232, "end_pos": 236, "sequence_org": "LQVDI", "sequence_mut": "GQGDG", "comment": "Strongly inhibits integrin-binding and activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 234, "end_pos": 236, "sequence_org": "VDI", "sequence_mut": "GDG", "comment": "Strongly inhibits integrin-binding and activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 237, "end_pos": 237, "sequence_org": "N", "sequence_mut": "A", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 254, "end_pos": 254, "sequence_org": "N", "sequence_mut": "A", "comment": "Does not affect integrin-binding or activation of TGF-beta-1.", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" }, { "database": "PubMed", "id": "28117447", "url": "https://glygen.org/publication/PubMed/28117447" } ] }, { "start_pos": 257, "end_pos": 260, 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"https://monarchinitiative.org/disease/MONDO:0001056", "name": "malignant tumour of greater curve of stomach", "description": "" }, { "id": "MONDO:0001056", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0001056", "name": "malignant tumour of lesser curve of stomach", "description": "" }, { "id": "MONDO:0001056", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0001056", "name": "malignant tumour of stomach", "description": "" }, { "id": "MONDO:0001056", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0001056", "name": "malignant tumour of the stomach", "description": "" }, { "id": "MONDO:0001056", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0001056", "name": "stomach cancer", "description": "" }, { "id": "MONDO:0001056", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0001056", "name": "Ca body - stomach", "description": "" }, { "id": "MONDO:0001056", 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176, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn176", "evidence": [ { "id": "P01137", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P01137#ptm_processing" }, { "id": "24190977", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/24190977" }, { "id": "GLY_000143", "database": "GlyGen", "url": "https://data.glygen.org/GLY_000143" }, { "id": "23090970", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/23090970" } ] }, { "glytoucan_ac": "G14260UH", "type": "N-linked", "subtype": "", "site_category": "reported_with_glycan", "site_seq": "N", "relation": "attached", "comment": "", "start_pos": 82, "start_aa": "Asn", "end_pos": 82, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn82", "evidence": [ { "id": "1835", "database": "GlyConnect", "url": "https://glyconnect.expasy.org/browser/proteins/1835" }, { "id": "29741879", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/29741879" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "reported", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 82, "start_aa": "Asn", "end_pos": 82, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn82", "evidence": [ { "id": "P01137", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P01137#ptm_processing" }, { "id": "16335952", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/16335952" }, { "id": "5FFO", "database": "RCSB PDB", "url": "https://www.rcsb.org/sequence/5FFO" }, { "id": "28117447", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/28117447" }, { "id": "16263699", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/16263699" }, { "id": "24190977", "database": "PubMed", "url": "https://glygen.org/publication/PubMed/24190977" }, { "id": "GLY_000143", "database": "GlyGen", "url": "https://data.glygen.org/GLY_000143" } ] } ], "phosphorylation": [], 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"date": "1999", "authors": "Donahue JE, Berzin TM, Rafii MS, Glass DJ, Yancopoulos GD, Fallon JR, Stopa EG", "evidence": [ { "database": "Reactome", "id": "R-HSA-3000178", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-3000178" } ], "reference": [ { "type": "PubMed", "id": "10339611", "url": "https://glygen.org/publication/PubMed/10339611" } ] }, { "title": "Regulation of the germline immunoglobulin Cgamma1 promoter by CD40 ligand and IL-4: dual role for tandem NF-kappaB binding sites.", "journal": "Molecular immunology", "date": "1999", "authors": "Warren WD, Roberts KL, Linehan LA, Berton MT", "evidence": [ { "database": "Reactome", "id": "R-HSA-6785807", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-6785807" } ], "reference": [ { "type": "PubMed", "id": "10369418", "url": "https://glygen.org/publication/PubMed/10369418" } ] }, { "title": "Ultrastructural distribution of 36-kD microfibril-associated glycoprotein (MAGP-36) in human and bovine tissues.", "journal": 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regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction", "id": "GO:0051897", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0051897", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of ERK1 and ERK2 cascade", "id": "GO:0070374", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0070374", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of protein phosphorylation", "id": "GO:0001933", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0001933", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "ATP biosynthetic process", "id": "GO:0006754", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0006754", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of vascular endothelial growth factor production", "id": "GO:0010575", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010575", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of interleukin-6 production", "id": "GO:0032755", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032755", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of protein dephosphorylation", "id": "GO:0035307", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0035307", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of DNA-templated transcription", "id": "GO:0045892", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045892", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of protein secretion", "id": "GO:0050714", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050714", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "cellular response to hypoxia", "id": "GO:0071456", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0071456", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "phosphate-containing compound metabolic process", "id": "GO:0006796", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0006796", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "response to wounding", "id": "GO:0009611", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0009611", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of protein-containing complex assembly", "id": "GO:0031334", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0031334", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "response to progesterone", "id": "GO:0032570", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032570", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of canonical NF-kappaB signal transduction", "id": "GO:0043123", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043123", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of DNA-templated transcription", "id": "GO:0045893", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045893", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of smooth muscle cell proliferation", "id": "GO:0048661", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048661", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "neural tube development", "id": "GO:0021915", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0021915", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of cell-cell adhesion", "id": "GO:0022408", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0022408", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of blood vessel endothelial cell migration", "id": "GO:0043537", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043537", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of epidermal growth factor receptor signaling pathway", "id": "GO:0045742", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045742", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of inflammatory response", "id": "GO:0050729", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050729", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of peptidyl-tyrosine phosphorylation", "id": "GO:0050731", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050731", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "regulation of cell migration", "id": "GO:0030334", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030334", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of tumor necrosis factor production", "id": "GO:0032760", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032760", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "cellular response to transforming growth factor beta stimulus", "id": "GO:0071560", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0071560", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "extrinsic apoptotic signaling pathway", "id": "GO:0097191", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0097191", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of protein localization to plasma membrane", "id": "GO:1903077", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:1903077", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of blood vessel endothelial cell migration", "id": "GO:0043536", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043536", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "sprouting angiogenesis", "id": "GO:0002040", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002040", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "membrane protein intracellular domain proteolysis", "id": "GO:0031293", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0031293", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of canonical Wnt signaling pathway", "id": "GO:0090263", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0090263", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "chondrocyte differentiation", "id": "GO:0002062", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002062", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of endothelial cell apoptotic process", "id": "GO:2000353", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:2000353", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of fat cell differentiation", "id": "GO:0045599", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045599", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of cell differentiation", "id": "GO:0045596", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045596", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "hematopoietic progenitor cell differentiation", "id": "GO:0002244", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002244", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of cell cycle", "id": "GO:0045786", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045786", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of hyaluronan biosynthetic process", "id": "GO:1900126", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:1900126", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of cardiac muscle cell differentiation", "id": "GO:2000727", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:2000727", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "protein export from nucleus", "id": "GO:0006611", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0006611", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of myoblast differentiation", "id": "GO:0045662", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045662", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target", "id": "GO:0002859", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002859", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "regulation of blood vessel remodeling", "id": "GO:0060312", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0060312", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of macrophage cytokine production", "id": "GO:0010936", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010936", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of extracellular matrix disassembly", "id": "GO:0010716", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010716", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of vascular permeability", "id": "GO:0043117", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043117", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of chemotaxis", "id": "GO:0050921", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050921", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "negative regulation of skeletal muscle tissue development", "id": "GO:0048642", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048642", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "salivary gland morphogenesis", "id": "GO:0007435", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007435", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of mesenchymal stem cell proliferation", "id": "GO:1902462", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:1902462", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "hyaluronan catabolic process", "id": "GO:0030214", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030214", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "receptor catabolic process", "id": "GO:0032801", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032801", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of miRNA transcription", "id": "GO:1902895", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:1902895", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "cellular response to low-density lipoprotein particle stimulus", "id": "GO:0071404", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0071404", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "response to cholesterol", "id": "GO:0070723", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0070723", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "cell-cell junction organization", "id": "GO:0045216", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045216", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of isotype switching to IgA isotypes", "id": "GO:0048298", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048298", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "heart valve morphogenesis", "id": "GO:0003179", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0003179", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "connective tissue replacement involved in inflammatory response wound healing", "id": "GO:0002248", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002248", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": "https://www.uniprot.org/uniprot/P01137" } ], "pmid": "" }, { "name": "positive regulation of chemokine (C-X-C motif) ligand 2 production", "id": "GO:2000343", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:2000343", "evidence": [ { "database": "UniProtKB", "id": "P01137", "url": 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