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programmed cell death protein 1; PDL1 receptor; protein PD-1; CD273 receptor; CD274 receptor; hPD-1 (PDCD1, hPD-1, CD279)

Function: - possible cell death inducer in association with ligands CD273 & CD274 (PD-L1) - inhibitory receptor expressed by T-cells - a checkpoint inhibitor Structure: - contains 1 Ig-like V-type domain Compartment: - membrane; single-pass type 1 membrane protein Expression: - expressed by T-cells - induced at programmed cell death Pathology: - genetic variation in PDCD1 is associated with susceptibility to systemic lupus erythematosus type 2 - expression on HIV1-specific T-cells is associated with T-cell exhaustion & disease progression [2] Pharmacology: - anti-PDCD1 antibody benefits 18-27% of patients with non-small-cell lung cancer, cutaneous melanoma or renal cell carcinoma [3] - pembrolizumab (Keytruda) & nivolumab (Opdivo) block ligand activation of the PD-1 receptor on activated T cells - PDCD1 is an inhibitory receptor expressed on activated tumor-specific CD4+ helper T-cells & CD8+ cytotoxic T-cells - its major ligand PD-L1 is expressed in many human cancers [3]

Interactions

molecular events

Related

apoptosis programmed cell death protein

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein membrane protein receptor

Properties

SIZE: MW = 32 kD entity length = 288 aa COMPARTMENT: cellular membrane MOTIF: signal sequence {1-20} immunoglobulin superfamily domain {35-145} MOTIF: N-glycosylation site {N49} cysteine residue {C54} MODIFICATION: cysteine residue {C123} N-glycosylation site {N58} N-glycosylation site {N74} N-glycosylation site {N116} cysteine residue {C123} MODIFICATION: cysteine residue {C54} transmembrane domain {171-191}

Database Correlations

OMIM correlations UniProt Q15116 Pfam PF07686 Entrez Gene 5133 Kegg hsa:5133

References

  1. UniProt :accession Q15116
  2. Day CL et al, PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006, 443:350 PMID: 16921384
  3. Topalian SL et al Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer N Engl J Med, June 2, 2012 PMID: 22658127 http://www.nejm.org/doi/full/10.1056/NEJMoa1200690