Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). 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 (By similarity). 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). Inhibited by pembrolizumab (also named MK-3475 or lambrolizumab), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:27734966, PubMed:27325296). 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). Monomer (PubMed:26602187). Interacts with CD274/PDCD1L1 (PubMed:26602187). Interacts with CD273/PDCD1LG2 (By similarity). Interacts with FBXO38; leading to ubiquitination and degradation of PDCD1 by the proteasome (PubMed:30487606). Induced at programmed cell death. 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). Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding. Phosphorylation at Tyr-248 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. 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 susceptibility is associated with variants affecting the gene represented in this entry.