CD274(Extracellular)

Full Name

CD274 Molecule

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).

Biological Process

Adaptive immune response Source: UniProtKB-KW
Cell surface receptor signaling pathway Source: UniProtKB
Cellular response to lipopolysaccharide Source: GO_Central
Immune response Source: UniProtKB
Negative regulation of activated T cell proliferation Source: UniProtKB
Negative regulation of CD4-positive, alpha-beta T cell proliferation Source: UniProtKB
Negative regulation of CD8-positive, alpha-beta T cell activation Source: UniProtKB
Negative regulation of interferon-gamma production Source: UniProtKB
Negative regulation of interleukin-10 production Source: UniProtKB
Negative regulation of T cell proliferation Source: GO_Central
Negative regulation of tumor necrosis factor superfamily cytokine production Source: UniProtKB
Positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process Source: UniProtKB
Positive regulation of cell migration Source: Ensembl
Positive regulation of interleukin-10 production Source: UniProtKB
Positive regulation of T cell proliferation Source: GO_Central
Positive regulation of tolerance induction to tumor cell Source: UniProtKB
Response to cytokine Source: AgBase
Signal transduction Source: UniProtKB
T cell costimulation Source: UniProtKB
Toxin transport Source: Ensembl

Cellular Location

Cell membrane; Early endosome membrane; Recycling endosome membrane. Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation.
Isoform 1: Cell membrane
Isoform 2: Endomembrane system

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).

Topology

Extracellular: 19-238
Helical: 239-259
Cytoplasmic: 260-290

PTM

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