Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells.
show all
Cellular Localization:
Cell membrane ; Single-pass type I membrane protein .
show all
Tissue Expression:
Expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells. Highly expressed in naive T-cells and B-cells but no expression on germinal center B-cells. Abnormally low expression in naive B-cells from HIV-1 infected patients. Very low expression in NK cells from a patient with chronic active Epstein-Barr virus infection.