CD274
GeneName
CD274
Summary
CD274, also known as PD-L1, PDL1, or B7-H1, is a 33 kDa transmembrane protein that is expressed on various cell types, including antigen-presenting cells, and plays a critical role in the regulation of immune responses. It is located on the external side of the plasma membrane and is involved in the negative regulation of T cell activation and proliferation through its interaction with the PD-1 receptor on T cells. CD274 is also implicated in the adaptive immune response and is involved in pathways such as T cell costimulation and cellular responses to cytokines. Additionally, it can be found in various cellular compartments, including the actin cytoskeleton, early endosomes, and extracellular exosomes, indicating its multifaceted roles in cellular signalling and immune modulation.
Importance
CD274 is relevant to: - Immune checkpoint therapy, particularly in cancer treatment, as it mediates immune evasion by tumours through PD-1 interaction. - Autoimmune diseases, where its regulation of T cell activity can influence disease progression. - The modulation of immune responses in infections, as it plays a role in the response to lipopolysaccharide and other immune stimuli. - Research into the mechanisms of T cell exhaustion and its implications for chronic infections and cancer.
Top Products
For researchers investigating CD274, we highly recommend the top-selling recombinant antibody, Anti-PD-L1 antibody [28-8] (ab205921). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including immunohistochemistry (IHC), western blotting (WB), flow cytometry (FC), and immunocytochemistry (ICC). With 592 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable detection of PD-L1. The Recombinant human PD-L1 protein (Active) ELISA Kit (ab280943), supported by 1 citation, is an excellent option for researchers looking to measure CD274 with confidence.
Abcam Product Citation Summary
The data indicates that CD274 (PD-L1) is being extensively studied in various human cancers, particularly in pancreatic cancer, thymic carcinoma, and non-small cell lung cancer (NSCLC). The use of Abcam antibodies for both immunohistochemistry and western blotting highlights the importance of CD274 in understanding immune evasion mechanisms and therapeutic responses in these contexts. Additionally, studies involving mouse models further support the translational relevance of these findings.
Abcam Product Citation Table
Function
Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). 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:28813410, PubMed:28813417, PubMed:36727298). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). Can also act as a transcription coactivator: in response to hypoxia, translocates into the nucleus via its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis (PubMed:32929201).
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:28813410, PubMed:28813417). 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
Autoimmune disease, multisystem, infantile-onset, 5
ADMIO5
An autosomal recessive disorder characterized by autoimmune manifestations apparent in the first months or years of life. ADMIO5 patients have complete insulin deficiency and type 1 diabetes mellitus with neonatal onset.
None
The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:28813410). Ubiquitinated by MARCHF8; leading to degradation (PubMed:34183449). Deubiquitinated by USP22; leading to stabilization (PubMed:31399419).
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.
Isoform 4
Widely expressed, highest in lung, liver and pituitary and in various peripheral blood cells, including neutrophils and some subtypes of lymphoid and myeloid cells.
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
- Nucleus
- Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation (PubMed:28813417). Translocates to the nucleus in response to hypoxia via its interaction with phosphorylated STAT3 (PubMed:32929201).
- Isoform 1
- Cell membrane
- Single-pass type I membrane protein
- Isoform 2
- Endomembrane system
- Single-pass type I membrane protein
- Isoform 4
- Secreted
Alternative names
CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1, Programmed cell death 1 ligand 1, PD-L1, PDCD1 ligand 1, Programmed death ligand 1, hPD-L1, B7 homolog 1, B7-H1
Database links
Other research areas
- Immunology & Infectious Disease