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Details on Person UniProt:Q15116 PDCD1
| Class:Id | ReferenceGeneProduct:61382 |
|---|---|
| _chainChangeLog | signal peptide:1-20 added on Fri February 6 2015;chain:21-288 added on Fri February 6 2015;signal peptide:1-20 for 61382 removed on Fri August 9 2019;chain:21-288 for 61382 removed on Fri August 9 2019;signal peptide:1-23 for 61382 added on Fri August 9 2019;chain:24-288 for 61382 added on Fri August 9 2019;signal peptide:1-23 for 61382 removed on Sun Nov 03 2024;chain:24-288 for 61382 removed on Sun Nov 03 2024;signal peptide:1-24 for 61382 added on Sun Nov 03 2024;chain:25-288 for 61382 added on Sun Nov 03 2024 |
| _displayName | UniProt:Q15116 PDCD1 |
| _timestamp | 2026-02-20 22:25:16 |
| chain | signal peptide:1-24 chain:25-288 |
| checksum | A5210FD40C304FB7 |
| comment | FUNCTION 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).FUNCTION 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).ACTIVITY REGULATION 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).SUBUNIT Monomer.INTERACTION Induced at programmed cell death.PTM 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).PTM 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).PTM 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).DISEASE The disease may be caused by variants affecting the gene represented in this entry. PDCD1 deficiency due to a homozygous frameshift mutation has been detected in a patient with severe tuberculosis and autoimmunity. The patient had depletion and dysfunction of multiple T and NK lymphocyte subsets and impaired gamma-IFN production. |
| description | recommendedName: fullName evidence="22"Programmed cell death protein 1 shortName evidence="22"Protein PD-1 shortName evidence="20 23"hPD-1 cdAntigenNameCD279/cdAntigenName |
| geneName | PDCD1 PD1 |
| identifier | Q15116 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Apoptosis Cell membrane Disulfide bond Glycoprotein Immunity Immunoglobulin domain Isopeptide bond Membrane Phosphoprotein Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2455454] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:4341137] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9645038] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9688885] Weiser, JD [InstanceEdit:9706439] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | PDCD1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990901] ENSEMBL:ENSG00000188389 PDCD1 [Homo sapiens] |
| secondaryIdentifier | PDCD1_HUMAN O00517 Q8IX89 |
| sequenceLength | 288 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:197604] PDCD1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:389736] p-Y223,Y248-PDCD1 [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:389737] O4'-phospho-L-tyrosine at 248 [ModifiedResidue:389741] O4'-phospho-L-tyrosine at 223 |
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No pathways have been reviewed or authored by UniProt:Q15116 PDCD1 (61382)
