UL16 binding protein 2 (representative: ULBP2) (ULBP2/5/6)

UL16 binding proteins 2, 5, and 6 (ULBP2/5/6) are stress-inducible cell surface glycoproteins distantly related to classical MHC class I proteins but lacking the capacity to bind peptides or interact with beta-2 microglobulin[1][2][3][4]. Their primary biological function is to serve as ligands for the activating immune receptor NKG2D, found on natural killer (NK) cells and some T cells. Engagement of ULBP2/5/6 with NKG2D activates NK cell cytotoxicity and cytokine production, making these ligands important players in innate immune surveillance, particularly in the detection and destruction of transformed or infected cells[1][3][4]. ULBP2/5/6 expression is upregulated in cells under stress (e.g., infection, malignancy), and tumors may evade immune destruction by shedding soluble forms of these ligands, thus interfering with NK cell function[6][7]. ULBP2/5/6 proteins are under investigation as biomarkers as well as experimental therapeutic targets for enhancing anti-tumor immunity[6].

Other names

RAET1HNKG2DL2ALCAN-alphaN2DL2RAET1GRAET1LUL16-binding proteinsNKG2D ligands

NKG2D activation (leading to NK cell cytotoxicity and cytokine release) Potential inhibition of cancer immune evasion by blocking soluble ULBP2/5/6 or upregulating their cell surface expression