UniProt Summary: Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full KLRK1-HCST-mediated activation and ultimate killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T-cells, it provides primarily costimulation for TCR-induced signals. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express KLRK1 ligands escape from immune surveillance mediated by NK cells. {ECO:0000269|PubMed:10426994, ECO:0000269|PubMed:10528161, ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:12740575, ECO:0000269|PubMed:12740576, ECO:0000269|PubMed:16002667, ECO:0000269|PubMed:16339517, ECO:0000269|PubMed:16582911, ECO:0000269|PubMed:18097042}.
Pfam DomainsGO Terms
Pfam Domains
DAP10
GO Terms
phosphatidylinositol 3-kinase binding
positive regulation of phosphatidylinositol 3-kinase signaling
regulation of phosphatidylinositol 3-kinase signaling
signaling receptor binding
cell surface
protein phosphorylation
positive regulation of intracellular signal transduction
regulation of immune response
phosphorylation
positive regulation of signal transduction
regulation of immune system process
positive regulation of cell communication
positive regulation of signaling
regulation of intracellular signal transduction
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)