HCST_HUMAN » Hematopoietic cell signal transducer

HCST_HUMAN » Hematopoietic cell signal transducer
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
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°
ΔGtransfer -29.6 kcal/mol
ΔGfold -11.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology Out
TM Segments 47-72 (47-73)
Pathways

Immune System (Reactome)

Natural killer cell mediated cytotoxicity (KEGG)

PDB none
OPM none
Complexes none
Interactions

1B08, Complex: NKG2D:1B08.MICA:HCST, PubMed

MICA, Complex: MICA:HCST:NKG2D

MICB, Complex: MICB:HCST:NKG2D, PubMed

NKG2D, Complex: HCST:NKG2D, PubMed

Domains

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