Function:
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, downregulating 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.
Subunit:
Interacts with SH2 domains of tyrosine-protein phosphatases PTPN6 and PTPN11. The interaction with PTPN6 is constitutive. Interacts with the SH2 domain of CSK.
Subcellular Location:
Cell membrane; Single-pass type I membrane protein.
Tissue Specificity:
Expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells. Highly expressed in na飗e T-cells and B-cells but no expression on germinal center B-cells. Abnormally low expression in naive B-cells from HISLV1 infected patients. Very low expression in NK cells from a patient with chronic active Epstein-Barr virus infection.
Post-translational modifications:
Phosphorylation at Tyr-251 and Tyr-281 activates it. May be phosphorylated by LCK.
N-glycosylated.
Similarity:
Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
Database links:
Entrez Gene: 159686 Human
Entrez Gene: 381229 Mouse
SwissProt: Q5T655 Human
Unigene: 253576 Human
Unigene: 300553 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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