|HCST_HUMAN » Hematopoietic cell signal transducer » DNAX-activation protein 10;Membrane protein DAP10;Transmembrane adapter protein KAP10;|
|Hydrophobic Thickness||35.2 ± 2.8 Å|
|Tilt Angle||0 ± 0°|
|Links||UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB|
|TM Segments||47-72 (47-73)|
Immune System (Reactome)
MICA, Complex: MICA:HCST:NKG2D
AA: 1-33, DAP10 membrane protein
AA: 27-93, DAP10 membrane protein
|UniProt annotation for HCST_HUMAN » Hematopoietic cell signal transducer|
|FUNCTION: 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. SUBUNIT: Interacts with CLEC5A (By similarity). Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP (By similarity). Homodimer; Disulfide-linked. Heterohexamer composed of four subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via transmembrane domain) with KLRK1 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell-mediated cytotoxicity. Interacts with PIK3R1 and GRB2. TISSUE SPECIFICITY: Predominantly expressed in hemopoietic cells such as NK cells, subset of T-cells and monocytes. Detected in leukocytes, spleen, and thymus. INDUCTION: By T-cell receptor (TCR) ligation, which leads to enhanced KLRK1-HCST cell surface expression. Down-regulated by IL21/interleukin-21 in T-cells and NK cells. MISCELLANEOUS: Silencing of HCST suppresses cytolytic activity of T-cells and NK cells.|
|UniProt features for HCST_HUMAN » Hematopoietic cell signal transducer|
SIGNAL 1 18 Potential. |
CHAIN 19 93 Hematopoietic cell signal transducer.
REGION 86 89 PIK3R1 binding site.
REGION 86 88 GRB2 binding site.
|Amino Acid Sequence for HCST_HUMAN » Hematopoietic cell signal transducer|
|MIHLGHILFL LLLPVAAAQT TPGERSSLPA FYPGTSGSCS GCGSLSLPLL AGLVAADAVA SLLIVGAVFL CARPRRSPAQ EDGKVYINMP GRG|