Pdcd1
Developmental stage
Induced at programmed cell death.
Function
Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11209085, PubMed:11698646, PubMed:21300912). Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:11015443, PubMed:11224527, PubMed:18287011, PubMed:18641123, PubMed:22641383). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:22641383). 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:11698646, PubMed:22641383). The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (By similarity).
Post-translational modifications
Ubiquitinated at Lys-235 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains.
Tyrosine phosphorylated at Tyr-225 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:11698646, PubMed:22641383). 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 (PubMed:22641383).
Tissue Specificity
Thymus-specific.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
CD279, Pd1, Pdcd1, Programmed cell death protein 1, Protein PD-1, mPD-1