HCST_RAT
ID HCST_RAT Reviewed; 79 AA.
AC Q6X9T8;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 89.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344;
RA Wittmann M.E., Bryceson Y.T., Dissen E.;
RT "Molecular cloning of rat DAP10 and DAP12.";
RL Submitted (MAR-2003) 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}.
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:Q9UBK5}.
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; AY247020; AAP79986.1; -; mRNA.
DR RefSeq; NP_001005900.1; NM_001005900.1.
DR AlphaFoldDB; Q6X9T8; -.
DR SMR; Q6X9T8; -.
DR STRING; 10116.ENSRNOP00000028287; -.
DR PaxDb; Q6X9T8; -.
DR PRIDE; Q6X9T8; -.
DR Ensembl; ENSRNOT00000028287; ENSRNOP00000028287; ENSRNOG00000020849.
DR GeneID; 474146; -.
DR KEGG; rno:474146; -.
DR UCSC; RGD:1359238; rat.
DR CTD; 10870; -.
DR RGD; 1359238; Hcst.
DR eggNOG; ENOG502TKP3; Eukaryota.
DR GeneTree; ENSGT00390000012777; -.
DR HOGENOM; CLU_196934_0_0_1; -.
DR InParanoid; Q6X9T8; -.
DR OMA; YINMPAR; -.
DR OrthoDB; 1625802at2759; -.
DR PhylomeDB; Q6X9T8; -.
DR TreeFam; TF338335; -.
DR Reactome; R-RNO-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR PRO; PR:Q6X9T8; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020849; Expressed in spleen and 19 other tissues.
DR Genevisible; Q6X9T8; RN.
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; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
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..79
FT /note="Hematopoietic cell signal transducer"
FT /id="PRO_0000330291"
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 /evidence="ECO:0000250"
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; 8205 MW; 380F4653D8A5BCBC CRC64;
MAPPGHLLFL FLLPVAASQT NEGSCSGCGP LSLPLLAGLV AADAVMSLLI VGVVFVCMRL
HSRPAQEDGR VYINMPGRG
