{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15116","secondaryAccessions":["O00517","Q8IX89"],"uniProtkbId":"PDCD1_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-04-17","entryVersion":208,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7851902"}],"value":"Programmed cell death protein 1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7851902"}],"value":"Protein PD-1"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26602187"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9332365"}],"value":"hPD-1"}]},"cdAntigenNames":[{"value":"CD279"}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7851902"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:8760"}],"value":"PDCD1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7851902"}],"value":"PD1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21276005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26602187"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31754127"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32184441"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37208329"}],"value":"Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:31754127, PubMed:32184441, PubMed:37208329). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005, PubMed:26602187). Following T-cell receptor (TCR) engagement, PDCD1 associates with TCR-CD3 in the immunological synapse and directly inhibits T-cell activation (PubMed:32184441). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:32184441)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22658127"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25034862"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25399552"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"28951311"}],"value":"The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28951311). The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:28951311). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:22658127, PubMed:25034862, PubMed:25399552)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22658127"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25034862"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25399552"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27325296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27734966"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28165004"}],"value":"Inhibited by pembrolizumab (also named MK-3475 or lambrolizumab), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:27325296, PubMed:27734966). Inhibited by nivolumab (also named ONO-4538, BMS-936558 or Opdivo), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:28165004). The interaction with nivolumab is not dependent on glycosylation and depends on a loop at the N-terminus (N-terminal loop, corresponding to residues 25-34) (PubMed:28165004). Targeting the interaction between PDCD1 and CD274/PDCD1L1 with pembrolizumab and nivolumab antibodies has demonstrated great promise as a strategy for controlling and eradicating cancer (PubMed:22658127, PubMed:25034862, PubMed:25399552). Pembrolizumab and nivolumab are used for treatment of patients with advanced melanoma (PubMed:25034862, PubMed:25399552). These antibodies are also effective against other cancers, such as non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin's lymphoma (PubMed:25034862)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26602187"}],"value":"Monomer"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15116","intActId":"EBI-4314328"},"interactantTwo":{"uniProtKBAccession":"Q9NZQ7","geneName":"CD274","intActId":"EBI-4314282"},"numberOfExperiments":20,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15116","intActId":"EBI-4314328"},"interactantTwo":{"uniProtKBAccession":"Q9NZQ7-1","geneName":"CD274","intActId":"EBI-15686469"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15116","intActId":"EBI-4314328"},"interactantTwo":{"uniProtKBAccession":"Q9BQ51","geneName":"PDCD1LG2","intActId":"EBI-16427978"},"numberOfExperiments":17,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15116","intActId":"EBI-4314328"},"interactantTwo":{"uniProtKBAccession":"Q06124","geneName":"PTPN11","intActId":"EBI-297779"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30487606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31754127"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"value":"Single-pass type I membrane protein","id":"SL-9905"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7851902"}],"value":"Induced at programmed cell death"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30487606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37208329"}],"value":"Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to its proteasomal degradation (PubMed:30487606). Ubiquitinated via 'Lys-48'-linked polyubiquitin chains (PubMed:30487606). Deubiquitinated and thus stabilized by USP5 (PubMed:37208329)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31754127"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32184441"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37208329"}],"value":"Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:31754127, PubMed:32184441). Phosphorylation at Tyr-248 by FYN promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:32184441). Phosphorylation at Thr-234 promotes the recruitment of the deubiquitinase USP5 (PubMed:37208329)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28165004"}],"value":"N-glycosylation at Asn-58 contains at least two N-acetylglucosamine units and one fucose (PubMed:28165004). N-glycosylation does not affect binding to nivolumab drug (PubMed:28165004)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Autoimmune disease, multisystem, infantile-onset, 4","diseaseAccession":"DI-06972","acronym":"ADMIO4","description":"An autosomal recessive immunologic disorder characterized by lymphoproliferative autoimmunity and onset of various autoimmune diseases in early childhood. 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The patient had depletion and dysfunction of multiple T and NK lymphocyte subsets and impaired gamma-IFN production"}]}}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":25,"modifier":"EXACT"},"end":{"value":288,"modifier":"EXACT"}},"description":"Programmed cell death protein 1","featureId":"PRO_0000014892"},{"type":"Topological domain","location":{"start":{"value":25,"modifier":"EXACT"},"end":{"value":170,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":171,"modifier":"EXACT"},"end":{"value":191,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological 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