CD274

Function

Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077).

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 (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). 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 (By similarity).

Involvement in disease

Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199).

Post-translational modifications

Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-L1/CD274 triggering its degradation.

Sequence similarities

Belongs to the immunoglobulin superfamily. BTN/MOG family.

Tissue specificity

Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes.

Cellular localization

• Cell membrane
• Single-pass type I membrane protein
• Early endosome membrane
• Single-pass type I membrane protein
• Recycling endosome membrane
• Single-pass type I membrane protein
• Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation.
• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Isoform 2
• Endomembrane system
• Single-pass type I membrane protein

Alternative names

• Programmed cell death 1 ligand 1
• PD-L1
• PDCD1 ligand 1
• Programmed death ligand 1
• hPD-L1
• B7 homolog 1
• B7-H1
• PDL1
• B7H1
• CD274
• PDCD1LG1
• PDCD1L1

Database links

• swissprot:Q9NZQ7

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

33275Da