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. Homodimer; Disulfide-linked. Interacts with KLRK1 to form a stable complex, which results in surface expression of both proteins, whereas alone, it is minimally expressed. Interacts with PIK3R1 and GRB2. Interacts with CLEC5A (By similarity). Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP. Heterohexamer composed of four subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via transmembrane domain) with KLRK1 isoform 1 (via transmembrane domain); the interaction is required for KLRK1 cell surface expression on naive NK cells and activated CD8(+) T-cells, but is dispensable on activated TYROBP-expressing NK cells. Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Interacts with CD300H (By similarity). Phosphorylated; PIK3R1 and GRB2 associate specifically with tyrosine-phosphorylated HCST. O-glycosylated. Mice exhibit low expression of KLRK1 in NK cells, but no expression in resting T-cells. KLRK1 expression is not induced upon T-cell activation, while it is up-regulated in activated NK cells; NK cells promote KLRK1-mediated tumor rejection due to substitution of HCST by DAP12/TYROBP. Mice lacking HCST exhibit antitumor phenotype; they show enhanced immunity against melanoma malignancies due to hyperactive functioning of a group of T-cells that share properties of both T-cells and NK cells (NKT cells). NKT cells exhibit increased cytokine production and cytotoxicity, leading to efficient killing of melanoma tumors. Upon activation, T regulatory cells (Tregs) maintain higher levels of IL2 and produced significantly lower amounts of IL10 and IFN-gamma cytokines. NKT cells activated by IL2 efficiently lyse B16-melanoma tumors in vitro in an KLRK1-independent way; The hyperactivity of NKT cells in these mice is not related to signaling of KLRK1. Immune reactivity to healthy cells that express KLRK1 ligands can happen under physiological conditions; NK cells are able to reject syngeneic bone marrow grafts when the bone marrow cells expressed sufficient KLRK1 ligand. Belongs to the DAP10 family.