{ "uniprot_canonical_ac": "P0DTU3-1", "uniprot_ac": "P0DTU3", "uniprot_id": "TRAR2_HUMAN", "mass": { "chemical_mass": 30989.0, "monoisotopic_mass": 30989.0 }, "refseq": {}, "gene_names": [ { "name": "TRA", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/P0DTU3", "id": "P0DTU3" } ], "protein_names": [ { "name": "T cell receptor alpha chain MC.7.G5", "resource": "UniProtKB", "type": "recommended", "url": "", "id": "P0DTU3" }, { "name": "MC.7.G5 TRA", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "P0DTU3" }, { "name": "TR alpha chain TRAV38-2DV8*01J31*01C*01", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "P0DTU3" } ], "function": [ { "annotation": "The alpha chain of TRAV38-2DV8*01J31*01C*01/TRBV25-1*01J2S3*01C2*01 alpha-beta T cell receptor (TR) clonotype that displays pan-cancer cell recognition via the invariant MR1 molecule. On CD8-positive T cell clone MC.7.G5, likely recognizes tumor-specific or -associated metabolite(s) essential for cancer cell survival, triggering killing of many cancer cell types including lung, melanoma, leukemia, colon, breast, prostate, bone and ovarian cancer cells. Mediates cancer cell cytotoxicity in an HLA-independent manner. Has no reactivity to healthy cells, even stressed or infected by bacteria (PubMed:31959982). Antigen recognition initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell differentiation into effector/memory T cells (By similarity).", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3#function" }, { "database": "UniProtKB", "id": "P01848", "url": "https://www.uniprot.org/uniprot/P01848#function" }, { "database": "PubMed", "id": "31959982", "url": "https://glygen.org/publication/PubMed/31959982" } ] } ], "disease": [], "snv": [], "mutagenesis": [], "expression_tissue": [], "expression_disease": [], "species": [ { "name": "Homo sapiens", "taxid": 9606, "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "common_name": "Human" } ], "gene": [ { "name": "TRA", "url": "https://www.uniprot.org/uniprot/P0DTU3", "locus": {} } ], "crossref": [ { "id": "cd07688", "url": "https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd07688", "database": "CDD", "categories": [ "Protein Classification" ] }, { "id": "TRA", "url": "http://www.genecards.org/cgi-bin/carddisp.pl?gene=TRA", "database": "GeneCards", "categories": [ "Gene Annotation", "Organism-specific" ] }, { "id": "12027", "url": "https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=12027", "database": "HGNC", "categories": [ "Organism-specific" ] }, { "id": "IPR003599", "url": "https://www.ebi.ac.uk/interpro/entry/IPR003599", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "IPR007110", "url": "https://www.ebi.ac.uk/interpro/entry/IPR007110", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "IPR013106", "url": "https://www.ebi.ac.uk/interpro/entry/IPR013106", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "IPR013783", "url": "https://www.ebi.ac.uk/interpro/entry/IPR013783", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "IPR015370", "url": "https://www.ebi.ac.uk/interpro/entry/IPR015370", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "IPR036179", "url": "https://www.ebi.ac.uk/interpro/entry/IPR036179", "database": "InterPro", "categories": [ "Protein Classification" ] }, { "id": "NX_P0DTU3", "url": "https://www.nextprot.org/entry/NX_P0DTU3", "database": "neXtProt", "categories": [ "Protein", "Organism-specific" ] }, { "id": "PTHR19433", "url": "http://www.pantherdb.org/panther/family.do?clsAccession=PTHR19433", "database": "PANTHER", "categories": [ "Protein Classification" ] }, { "id": "PTHR19433:SF72", "url": "http://www.pantherdb.org/panther/family.do?clsAccession=PTHR19433:SF72", "database": "PANTHER", "categories": [ "Protein Classification" ] }, { "id": "PF07686", "url": "http://pfam.xfam.org/family/PF07686", "database": "Pfam", "categories": [ "Protein Classification" ] }, { "id": "PF09291", "url": "http://pfam.xfam.org/family/PF09291", "database": "Pfam", "categories": [ "Protein Classification" ] }, { "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3", "database": "UniProtKB", "categories": [ "Protein" ] }, { "id": "P0DTU3-1", "url": "https://www.uniprot.org/uniprot/P0DTU3-1", "database": "UniProtKB", "categories": [ "Protein" ] } ], "sequence": { "sequence": "MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRSAVNARLMFGDGTQLVVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS", "length": 275, "header": "sp|P0DTU3-1|TRAR2_HUMAN Isoform 1 of T cell receptor alpha chain MC.7.G5 OS=Homo sapiens OX=9606 GN=TRA PE=1 SV=1 CANONICAL=P0DTU3-1" }, "isoforms": [ { "isoform_ac": "P0DTU3-1", "url": "", "sequence": { "sequence": "MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRSAVNARLMFGDGTQLVVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS", "length": 275, "header": "sp|P0DTU3-1|TRAR2_HUMAN Isoform 1 of T cell receptor alpha chain MC.7.G5 OS=Homo sapiens OX=9606 GN=TRA PE=1 SV=1 CANONICAL=P0DTU3-1" }, "locus": {} } ], "glycosylation": [ { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "reported", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 167, "start_aa": "Asn", "end_pos": 167, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn167", "evidence": [ { "id": "P0DTU3", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P0DTU3#ptm_processing" }, { "id": "PRU00498", "database": "PROSITE-PRORULE", "url": "https://prosite.expasy.org/rule/PRU00498" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "reported", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 201, "start_aa": "Asn", "end_pos": 201, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn201", "evidence": [ { "id": "P0DTU3", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P0DTU3#ptm_processing" }, { "id": "PRU00498", "database": "PROSITE-PRORULE", "url": "https://prosite.expasy.org/rule/PRU00498" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "reported", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 212, "start_aa": "Asn", "end_pos": 212, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn212", "evidence": [ { "id": "P0DTU3", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P0DTU3#ptm_processing" }, { "id": "PRU00498", "database": "PROSITE-PRORULE", "url": "https://prosite.expasy.org/rule/PRU00498" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "reported", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 248, "start_aa": "Asn", "end_pos": 248, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn248", "evidence": [ { "id": "P0DTU3", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P0DTU3#ptm_processing" }, { "id": "PRU00498", "database": "PROSITE-PRORULE", "url": "https://prosite.expasy.org/rule/PRU00498" } ] }, { "glytoucan_ac": "", "type": "N-linked", "subtype": "", "site_category": "predicted", "site_seq": "N", "relation": "attached", "comment": "N-linked (GlcNAc...) asparagine", "start_pos": 78, "start_aa": "Asn", "end_pos": 78, "end_aa": "Asn", "residue": "Asn", "site_lbl": "Asn78", "evidence": [ { "id": "P0DTU3", "database": "UniProtKB", "url": "https://www.uniprot.org/uniprot/P0DTU3#ptm_processing" } ] } ], "phosphorylation": [], "glycation": [], "keywords": [ "glycoprotein", "glycoprotein_reported", "glycoprotein_predicted" ], "publication": [ { "title": "Protein displays of the human T cell receptor alpha, beta, gamma and delta variable and joining regions.", "journal": "Exp. Clin. Immunogenet.", "date": "2000", "authors": "Folch G, Scaviner D, Contet V, Lefranc M P", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "11096259", "url": "https://glygen.org/publication/PubMed/11096259" } ] }, { "title": "A clonotype nomenclature for T cell receptors.", "journal": "Immunogenetics", "date": "2009", "authors": "Yassai Maryam B, Naumov Yuri N, Naumova Elena N, Gorski Jack", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "19568742", "url": "https://glygen.org/publication/PubMed/19568742" } ] }, { "title": "Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1.", "journal": "Nature immunology", "date": "2020", "authors": "Crowther MD, Dolton G, Legut M, Caillaud ME, Lloyd A, Attaf M, Galloway SAE, Rius C, Farrell CP, Szomolay B, Ager A, Parker AL, Fuller A, Donia M, McCluskey J, Rossjohn J, Svane IM, Phillips JD, Sewell AK", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "31959982", "url": "https://glygen.org/publication/PubMed/31959982" } ] }, { "title": "Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "date": "1985", "authors": "Yanagi Y, Chan A, Chin B, Minden M, Mak T W", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "3873654", "url": "https://glygen.org/publication/PubMed/3873654" } ] }, { "title": "The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukaemia.", "journal": "EMBO J.", "date": "1985", "authors": "Rabbitts T H, Lefranc M P, Stinson M A, Sims J E, Schroder J, Steinmetz M, Spurr N L, Solomon E, Goodfellow P N", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "3875483", "url": "https://glygen.org/publication/PubMed/3875483" } ] }, { "title": "Analysis of the 1.1-Mb human alpha/delta T-cell receptor locus with bacterial artificial chromosome clones.", "journal": "Genome Res.", "date": "1997", "authors": "Boysen C, Simon M I, Hood L", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "reference": [ { "type": "PubMed", "id": "9110172", "url": "https://glygen.org/publication/PubMed/9110172" } ] } ], "pathway": [], "orthologs": [], "go_annotation": { "categories": [ { "name": "Biological Process", "total": 3, "go_terms": [ { "name": "response to bacterium", "id": "GO:0009617", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0009617", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "pmid": "" }, { "name": "detection of tumor cell", "id": "GO:0002355", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002355", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "pmid": "" }, { "name": "T cell mediated cytotoxicity directed against tumor cell target", "id": "GO:0002419", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0002419", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "pmid": "" } ] }, { "name": "Cellular Component", "total": 1, "go_terms": [ { "name": "alpha-beta T cell receptor complex", "id": "GO:0042105", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0042105", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "pmid": "" } ] }, { "name": "Molecular Function", "total": 1, "go_terms": [ { "name": "signaling receptor activity", "id": "GO:0038023", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0038023", "evidence": [ { "database": "UniProtKB", "id": "P0DTU3", "url": "https://www.uniprot.org/uniprot/P0DTU3" } ], "pmid": "" } ] } ] }, "pro_annotation": [], "site_annotation": [ { "start_pos": 167, "end_pos": 169, "annotation": "n_glycosylation_sequon" }, { "start_pos": 201, "end_pos": 203, "annotation": "n_glycosylation_sequon" }, { 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