HCST_BOVIN
ID HCST_BOVIN Reviewed; 79 AA.
AC Q1XF11;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 87.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH KLRK1, SUBCELLULAR LOCATION,
RP SUBUNIT, AND FUNCTION.
RC TISSUE=Peripheral blood;
RX PubMed=17530242; DOI=10.1007/s00251-007-0226-6;
RA Fikri Y., Nyabenda J., Content J., Huygen K.;
RT "Cloning, sequencing, and cell surface expression pattern of bovine
RT immunoreceptor NKG2D and adaptor molecules DAP10 and DAP12.";
RL Immunogenetics 59:653-659(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ovary;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
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, ECO:0000269|PubMed:17530242}.
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 KLRK1.
CC Interacts with CD300H (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9UBK5, ECO:0000269|PubMed:17530242}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:17530242}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:17530242}.
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; AM075813; CAJ27508.1; -; mRNA.
DR EMBL; BC142038; AAI42039.1; -; mRNA.
DR RefSeq; NP_001070445.1; NM_001076977.2.
DR AlphaFoldDB; Q1XF11; -.
DR SMR; Q1XF11; -.
DR STRING; 9913.ENSBTAP00000009651; -.
DR PaxDb; Q1XF11; -.
DR Ensembl; ENSBTAT00000009651; ENSBTAP00000009651; ENSBTAG00000007336.
DR GeneID; 767892; -.
DR KEGG; bta:767892; -.
DR CTD; 10870; -.
DR VEuPathDB; HostDB:ENSBTAG00000007336; -.
DR VGNC; VGNC:29783; HCST.
DR eggNOG; ENOG502TKP3; Eukaryota.
DR GeneTree; ENSGT00390000012777; -.
DR HOGENOM; CLU_196934_0_0_1; -.
DR InParanoid; Q1XF11; -.
DR OMA; YINMPAR; -.
DR OrthoDB; 1625802at2759; -.
DR TreeFam; TF338335; -.
DR Proteomes; UP000009136; Chromosome 18.
DR Bgee; ENSBTAG00000007336; Expressed in blood and 85 other tissues.
DR ExpressionAtlas; Q1XF11; baseline.
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; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
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 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..79
FT /note="Hematopoietic cell signal transducer"
FT /id="PRO_0000330286"
FT TOPO_DOM 19..35
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 72..75
FT /note="PIK3R1 binding site"
FT REGION 72..74
FT /note="GRB2 binding site"
FT /evidence="ECO:0000250"
FT MOD_RES 72
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBK5"
SQ SEQUENCE 79 AA; 8218 MW; AE8850BEA984F974 CRC64;
MVPPGNILFL LLLPVATAQM TPGSCSGCGP LSLPLLAGLV AADAVVSLLI VVVVFVCARL
RSRPTQEDDK IYINMPGRG
