V-set domain-containing T-cell activation inhibitor 1; immune costimulatory protein B7-H4; B7h.5; T-cell costimulatory molecule B7x; protein B7S1 (VTCN1, B7H4, UNQ659/PRO1291)
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Function
- negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production & development of cytotoxicity
- when expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells in suppression of tumor-associated antigen-specific T-cell immunity
- role in promoting epithelial cell transformation
- N-glycosylated
Structure
- belongs to the immunoglobulin superfamily, BTN/MOG family
- contains 2 Ig-like V-type domain (immunoglobulin-like)
Compartment
- cell membrane
- expressed at the cell surface
- soluble form has also been detected
Alternative splicing
named isoforms=3
Expression
- widely expressed, including in kidney, liver, lung, ovary, placenta, spleen & testis
- expressed on activated T- & B-cells, monocytes & dendritic cells, but not expressed in most normal tissues (at protein level)
- up-regulated by IL-6 & IL-10 & inhibited by GM-CSF & IL-4 on antigen-presenting cells (APCs)
Pathology
- overexpressed in breast cancer, ovarian cancer, endometrial cancer, renal cell carcinoma & non-small-cell lung cancers
- may serve as a predictive marker for renal cell carcinoma
Comparative biology
- the mouse ortholog is a GPI-anchored protein but the Gly which is predicted to be the modified site in mouse & rat is not conserved in human