PDCD1
entrez
5133
canonical
uniprot
Q15116
canonical
ensembl
ENSG00000188389
resolver
ensembl
ENSG00000276977
resolver
ensp
ENSP00000335062
resolver
ensp
ENSP00000480684
resolver
ensp
ENSP00000520841
resolver
enst
ENST00000334409
resolver
enst
ENST00000618185
resolver
enst
ENST00000718474
resolver
genesymbol
PDCD1
resolver
genesymbol_syn
PD1
resolver
hgnc
HGNC:8760
resolver
uniprot
A0A0M3M0G7
resolver
uniprot
A0ABB0MVI3
resolver
uniprot
O00517
resolver
uniprot
Q8IX89
resolver
uniprot_entry
A0A0M3M0G7_HUMAN
resolver
uniprot_entry
A0ABB0MVI3_HUMAN
resolver
uniprot_entry
PDCD1_HUMAN
resolver
uniprot_sec
O00517
resolver
uniprot_sec
Q8IX89
resolver
activity_regulation
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). {ECO:0000269|PubMed:22658127, ECO:0000269|PubMed:25034862, ECO:0000269|PubMed:25399552, ECO:0000269|PubMed:27325296, ECO:0000269|PubMed:27734966, ECO:0000269|PubMed:28165004}.
uniprot
proteins
amino_acid_sequence
MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGSLVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVPCVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL
uniprot
proteins
disease_involvement
DISEASE: Autoimmune disease, multisystem, infantile-onset, 4 (ADMIO4) [MIM:621004]: An autosomal recessive immunologic disorder characterized by lymphoproliferative autoimmunity and onset of various autoimmune diseases in early childhood. Death from autoimmune pneumonitis may occur. {ECO:0000269|PubMed:34183838}. Note=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. {ECO:0000269|PubMed:34183838}.
uniprot
proteins
function
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). {ECO:0000269|PubMed:21276005, ECO:0000269|PubMed:26602187, ECO:0000269|PubMed:31754127, ECO:0000269|PubMed:32184441, ECO:0000269|PubMed:37208329}.; 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). {ECO:0000269|PubMed:22658127, ECO:0000269|PubMed:25034862, ECO:0000269|PubMed:25399552, ECO:0000303|PubMed:28951311}.
uniprot
proteins
mass_dalton
31647
uniprot
proteins
mutagenesis
MUTAGEN 49; /note="N->A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug."; /evidence="ECO:0000269|PubMed:28165004"; MUTAGEN 58; /note="N->A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug."; /evidence="ECO:0000269|PubMed:28165004"; MUTAGEN 74; /note="N->A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug."; /evidence="ECO:0000269|PubMed:28165004"; MUTAGEN 116; /note="N->A: Decreased N-glycosylation without affecting binding to binding to nivolumab drug."; /evidence="ECO:0000269|PubMed:28165004"; MUTAGEN 210; /note="K->R: Does not affect ubiquitination by the SCF(FBXO38) complex."; /evidence="ECO:0000269|PubMed:30487606"; MUTAGEN 223; /note="Y->F: Reduced tyrosine phosphorylation without affecting ability to mediate recruitment of PTPN11/SHP-2."; /evidence="ECO:0000269|PubMed:32184441"; MUTAGEN 233; /note="K->R: Abolishes ubiquitination by the SCF(FBXO38) complex."; /evidence="ECO:0000269|PubMed:30487606"; MUTAGEN 248; /note="Y->F: Reduced tyrosine phosphorylation. Abolished ability to mediate recruitment of PTPN11/SHP-2."; /evidence="ECO:0000269|PubMed:32184441
uniprot
proteins
post_translational_modification
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). {ECO:0000269|PubMed:30487606, ECO:0000269|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). {ECO:0000269|PubMed:31754127, ECO:0000269|PubMed:32184441, ECO:0000269|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). {ECO:0000269|PubMed:28165004}.
uniprot
proteins
pubmed
12402038
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
21276005
uniprot
proteins
pubmed
22658127
uniprot
proteins
pubmed
23417675
uniprot
proteins
pubmed
25034862
uniprot
proteins
pubmed
25399552
uniprot
proteins
pubmed
26602187
uniprot
proteins
pubmed
27325296
uniprot
proteins
pubmed
27618663
uniprot
proteins
pubmed
27734966
uniprot
proteins
pubmed
28165004
uniprot
proteins
pubmed
28951311
uniprot
proteins
pubmed
30487606
uniprot
proteins
pubmed
31754127
uniprot
proteins
pubmed
32184441
uniprot
proteins
pubmed
34183838
uniprot
proteins
pubmed
37208329
uniprot
proteins
pubmed
7851902
uniprot
proteins
pubmed
9332365
uniprot
proteins
sequence_length
288
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30487606, ECO:0000269|PubMed:31754127}; Single-pass type I membrane protein.
uniprot
proteins
transmembrane_region
TRANSMEM 171..191; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins