Q9QUJ0 · HCST_MOUSE

  • Protein
    Hematopoietic cell signal transducer
  • Gene
    Hcst
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 a 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.

Miscellaneous

Immune reactivity to healthy cells that express KLRK1 ligands can happen under physiological conditions; NK cells are able to reject syngeneic bone marrow grafts when the bone marrow cells expressed sufficient KLRK1 ligand.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcell surface
Cellular Componentmembrane
Molecular Functionphosphatidylinositol 3-kinase binding
Molecular Functionsignaling receptor binding
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processregulation of immune response

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Hematopoietic cell signal transducer
  • Alternative names
    • DNAX-activation protein 10
    • Membrane protein DAP10
    • Transmembrane adapter protein KAP10

Gene names

    • Name
      Hcst
    • Synonyms
      Dap10, Kap10

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9QUJ0
  • Secondary accessions
    • Q9R1E7

Proteomes

Organism-specific databases

Subcellular Location

Membrane
; Single-pass type I membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain18-35Extracellular
Transmembrane36-56Helical
Topological domain57-79Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Mice exhibit low expression of KLRK1 in NK cells, but no expression in resting T-cells. KLRK1 expression is not induced upon T-cell activation, while it is up-regulated in activated NK cells; NK cells promote KLRK1-mediated tumor rejection due to substitution of HCST by DAP12/TYROBP. Mice lacking HCST exhibit antitumor phenotype; they show enhanced immunity against melanoma malignancies due to hyperactive functioning of a group of T-cells that share properties of both T-cells and NK cells (NKT cells). NKT cells exhibit increased cytokine production and cytotoxicity, leading to efficient killing of melanoma tumors. Upon activation, T regulatory cells (Tregs) maintain higher levels of IL2 and produced significantly lower amounts of IL10 and IFN-gamma cytokines. NKT cells activated by IL2 efficiently lyse B16-melanoma tumors in vitro in an KLRK1-independent way; The hyperactivity of NKT cells in these mice is not related to signaling of KLRK1.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, modified residue.

TypeIDPosition(s)Description
Signal1-17
ChainPRO_000033029018-79Hematopoietic cell signal transducer
Modified residue72Phosphotyrosine

Post-translational modification

Phosphorylated; PIK3R1 and GRB2 associate specifically with tyrosine-phosphorylated HCST.
O-glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer; Disulfide-linked. Interacts with KLRK1 to form a stable complex, which results in surface expression of both proteins, whereas alone, it is minimally expressed. Interacts with PIK3R1 and GRB2. Interacts with CLEC5A (By similarity).
Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP. Heterohexamer composed of four subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via transmembrane domain) with KLRK1 isoform 1 (via transmembrane domain); the interaction is required for KLRK1 cell surface expression on naive NK cells and activated CD8+ T-cells, but is dispensable on activated TYROBP-expressing NK cells. Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Interacts with CD300H (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q9QUJ0Clec5a Q9R0073EBI-15761243, EBI-15761206
BINARY Q9QUJ0Tyrobp O548854EBI-15761243, EBI-15687058

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region72-74GRB2 binding site
Region72-75PIK3R1 binding site

Sequence similarities

Belongs to the DAP10 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 2 isoforms produced by Alternative splicing.

Q9QUJ0-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    79
  • Mass (Da)
    8,114
  • Last updated
    2000-05-01 v1
  • Checksum
    B411985277D601E3
MDPPGYLLFLLLLPVAASQTSAGSCSGCGTLSLPLLAGLVAADAVMSLLIVGVVFVCMRPHGRPAQEDGRVYINMPGRG

Q9QUJ0-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_03302315-22in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF172930
EMBL· GenBank· DDBJ
AAD50294.1
EMBL· GenBank· DDBJ
mRNA
AF072846
EMBL· GenBank· DDBJ
AAD46988.1
EMBL· GenBank· DDBJ
mRNA
AF122905
EMBL· GenBank· DDBJ
AAD47912.1
EMBL· GenBank· DDBJ
mRNA
AF358138
EMBL· GenBank· DDBJ
AAK52752.1
EMBL· GenBank· DDBJ
Genomic DNA
AK008005
EMBL· GenBank· DDBJ
BAB25404.1
EMBL· GenBank· DDBJ
mRNA
BC069220
EMBL· GenBank· DDBJ
AAH69220.1
EMBL· GenBank· DDBJ
mRNA
BC145824
EMBL· GenBank· DDBJ
AAI45825.1
EMBL· GenBank· DDBJ
mRNA
BC145826
EMBL· GenBank· DDBJ
AAI45827.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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