UL16-binding protein 6 (ULBP-6) (ULBP6)

UL16-binding protein 6 (ULBP-6), also known as ULBP6 or RAET1L, is a polymorphic glycoprotein encoded on human chromosome 6q24.2-q25.3 that functions as a ligand for the activating immunoreceptor NKG2D, expressed on natural killer (NK) cells and certain T cells. It shares structural similarity with MHC class I molecules in its alpha-1 and alpha-2 domains but lacks the alpha-3 domain and is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) linkage. ULBP-6 exhibits a more restricted expression profile compared to other ULBP family members (ULBP1-5), with detection in specific cell lines and primary tissues, including human papillomavirus-positive cervical carcinoma cells, and inducibility upon human cytomegalovirus (HCMV) infection. HCMV's UL16 protein binds ULBP-6 intracellularly, retaining it within the cell and preventing surface expression to evade NK cell recognition. Surface expression of ULBP-6 enhances NK cell killing and activation, correlating with its binding affinity to NKG2D. In disease contexts, ULBP-6 upregulation signals cellular stress from tumors or viral infections, contributing to immunosurveillance, though its evasion by pathogens like HCMV highlights immune regulatory challenges.[1][2][4]

Other names

ULBP6RAET1L