ID   HCST_MACFA              Reviewed;          78 AA.
AC   Q70RD5;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   25-MAY-2022, entry version 43.
DE   RecName: Full=Hematopoietic cell signal transducer;
DE   AltName: Full=DNAX-activation protein 10;
DE   AltName: Full=Membrane protein DAP10;
DE   Flags: Precursor;
GN   Name=HCST; Synonyms=DAP10;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lymphoid tissue;
RX   PubMed=15843571; DOI=10.4049/jimmunol.174.9.5695;
RA   Biassoni R., Fogli M., Cantoni C., Costa P., Conte R., Koopman G.,
RA   Cafaro A., Ensoli B., Moretta A., Moretta L., De Maria A.;
RT   "Molecular and functional characterization of NKG2D, NKp80, and NKG2C
RT   triggering NK cell receptors in rhesus and cynomolgus macaques: monitoring
RT   of NK cell function during simian HIV infection.";
RL   J. Immunol. 174:5695-5705(2005).
CC   -!- FUNCTION: Transmembrane adapter protein which associates with KLRK1 to
CC       form an activation receptor KLRK1-HCST in lymphoid and myeloid cells;
CC       this receptor plays a major role in triggering cytotoxicity against
CC       target cells expressing cell surface ligands such as MHC class I chain-
CC       related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands
CC       are up-regulated by stress conditions and pathological state such as
CC       viral infection and tumor transformation. Functions as docking site for
CC       PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST
CC       triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK,
CC       and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required
CC       for full KLRK1-HCST-mediated activation and ultimate killing of target
CC       cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity
CC       and enhances cytokine production initiated via DAP12/TYROBP-associated
CC       receptors. In T-cells, it provides primarily costimulation for TCR-
CC       induced signals. KLRK1-HCST receptor plays a role in immune
CC       surveillance against tumors and is required for cytolysis of tumors
CC       cells; indeed, melanoma cells that do not express KLRK1 ligands escape
CC       from immune surveillance mediated by NK cells (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer; Disulfide-linked. Heterohexamer composed of four
CC       subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via
CC       transmembrane domain) with KLRK1 (via transmembrane domain); the
CC       interaction is required for KLRK1 NK cell surface and induces NK cell-
CC       mediated cytotoxicity. Interacts with PIK3R1 and GRB2. Interacts with
CC       CLEC5A. Forms an CLEC5A/TYROBP/HCST trimolecular complex depending
CC       almost solely on TYROBP (By similarity). Interacts with CD300H (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:O43914}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- PTM: Phosphorylated; PIK3R1 and GRB2 associate specifically with
CC       tyrosine-phosphorylated HCST. {ECO:0000250}.
CC   -!- PTM: O-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the DAP10 family. {ECO:0000305}.
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DR   EMBL; AJ554300; CAD86941.1; -; mRNA.
DR   AlphaFoldDB; Q70RD5; -.
DR   SMR; Q70RD5; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IEA:InterPro.
DR   GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR   GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:InterPro.
DR   GO; GO:0050776; P:regulation of immune response; IEA:InterPro.
DR   InterPro; IPR009861; HCST.
DR   PANTHER; PTHR21409; PTHR21409; 1.
DR   Pfam; PF07213; DAP10; 1.
PE   3: Inferred from homology;
KW   Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Reference proteome;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..78
FT                   /note="Hematopoietic cell signal transducer"
FT                   /id="PRO_0000330288"
FT   TOPO_DOM        19..34
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        35..55
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        56..78
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          71..74
FT                   /note="PIK3R1 binding site"
FT                   /evidence="ECO:0000250"
FT   REGION          71..73
FT                   /note="GRB2 binding site"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         71
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UBK5"
SQ   SEQUENCE   78 AA;  7893 MW;  BFC680B5056CDF28 CRC64;
     MIHPGHILFL LLLPVAAAQT TPGSCSGCGS LSLPLLAGLV AADAVASLLI VGAVFLCARP
     RRSPAQDGKV YINMPGRG