| Function | Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self. Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. 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. 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. The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function. 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. |
| Protein Name | Programmed Cell Death Protein 1Protein Pd-1Hpd-1Cd Antigen Cd279 |
| Database Links | Reactome: R-HSA-389948Reactome: R-HSA-9679191 |
| Cellular Localisation | Cell MembraneSingle-Pass Type I Membrane Protein |
| Alternative Protein Names | Programmed Cell Death Protein 1 proteinProtein Pd-1 proteinHpd-1 proteinCd Antigen Cd279 proteinPDCD1 proteinPD1 protein |
Information sourced from Uniprot.org
