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This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
CD274, also commonly referred to as PDL1, is a ligand that binds with the receptor PD1, commonly found on T-cells, and acts to block T-cell activation. PD1 expression has been observed in a variety of cancers including melanoma and non-small cell lung cancer. The interaction of PD1/PDL1 is hypothesized to be a possible mechanism for the tumor to escape immune response. A number of checkpoint blockade inhibitors including pembrolizumab and nivolumab have been developed that target the PD1/PDL1 interaction in order to allow T-cells to recognize tumor cells without being deactivated by the tumor.
CD274 (CD274 Molecule) is a Protein Coding gene. Diseases associated with CD274 include Testicular Lymphoma and Smoldering Myeloma. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. An important paralog of this gene is PDCD1LG2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005515 | protein binding | IPI | 18585785 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005768 | endosome | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0009897 | external side of plasma membrane | IBA | 21873635 |
GO:0009986 | cell surface | IBA | 21873635 |
GO:0012505 | endomembrane system | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | NF-kappaB Signaling | ||
2 | Cell adhesion molecules (CAMs) | ||
3 | T cell receptor signaling pathway | ||
4 | Class I MHC mediated antigen processing and presentation | ||
5 | CD28 co-stimulation |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002250 | adaptive immune response | IEA | -- |
GO:0002376 | immune system process | IEA | -- |
GO:0002845 | positive regulation of tolerance induction to tumor cell | IMP | 28813410 |
GO:0006955 | immune response | IBA,IDA | 10581077 |
GO:0007165 | signal transduction | IBA,IDA | 10581077 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Atezolizumab | Approved, Investigational | Pharma | Target, antibody | 439 | ||
avelumab | Approved, Investigational | Pharma | Target, antagonist | 0 | ||
Durvalumab | Approved, Investigational | Pharma | Target, inhibitor, antibody | 469 | ||
nivolumab | Approved | Pharma | Therapeutic Antibodies, Immunotherapies | 1165 | ||
Pembrolizumab | Approved | Pharma | 1266 |
ExUns: | 1a | · | 1b | ^ | 2a | · | 2b | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6a | · | 6b | ^ | 7 | ^ | 8 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||
SP3: | - | ||||||||||||||||||||||
SP4: | - | - |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CD274 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CD274 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CD274 30 |
|
||
PD-L1 31 |
|
OneToOne | |||
Rat (Rattus norvegicus) |
Mammalia | Cd274 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Cd274 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CD274 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | CD274 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | CD274 30 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | cd274 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | si:ch211-241b2.5 30 |
|
||
CD274 31 |
|
OneToMany |
Disorder | Aliases | PubMed IDs |
---|---|---|
testicular lymphoma |
|
|
smoldering myeloma |
|
|
lymphoepithelioma-like carcinoma |
|
|
pleomorphic carcinoma |
|
|
penile cancer |
|
|