PD1 Recombinant Rabbit Monoclonal Antibody [SJ01-91] (ET1606-41)

UNIPROT #

Q15116

PROTEIN NAME

PD1

SYNONYMS

CD279 antibody;CD279 antigen antibody;hPD 1 antibody;hPD l antibody;hPD-1 antibody;hSLE1 antibody;PD 1 antibody;PD-1 antibody;PD1 antibody;PDCD 1 antibody;PDCD1 antibody;PDCD1_HUMAN antibody;Programmed cell death 1 antibody;Programmed cell death 1 protein antibody;Programmed cell death protein 1 antibody;Protein PD 1 antibody;Protein PD-1 antibody;SLEB2 antibody;Systemic lupus erythematosus susceptibility 2 antibody

DEVELOPMENTAL STAGE

Induced at programmed cell death.

POST-TRANSLATIONAL MODIFICATION

Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains.; 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 consists of two N-acetylglucosamine units and one fucose. N-glycosylation does not affect binding to nivolumab drug.

SUBCELLULAR LOCATION

Membrane.

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. 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). 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. Pembrolizumab and nivolumab are used for treatment of patients with advanced melanoma. These antibodies are also effective against other cancers, such as non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin's lymphoma.