PD1

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:11698646, PubMed:11209085, PubMed:21300912). Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:11015443, PubMed:11224527, PubMed:22641383, PubMed:18287011, PubMed:18641123). 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

• Programmed cell death protein 1
• Protein PD-1
• mPD-1
• Pd1
• Pdcd1

Database links

• entrezGene:18566
• swissprot:Q02242

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

31842Da