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    HCST hematopoietic cell signal transducer [ Homo sapiens (human) ]

    Gene ID: 10870, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HCSTprovided by HGNC
    Official Full Name
    hematopoietic cell signal transducerprovided by HGNC
    Primary source
    HGNC:HGNC:16977
    See related
    Ensembl:ENSG00000126264 MIM:604089; AllianceGenome:HGNC:16977
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DAP10; KAP10; PIK3AP
    Summary
    This gene encodes a transmembrane signaling adaptor that contains a YxxM motif in its cytoplasmic domain. The encoded protein may form part of the immune recognition receptor complex with the C-type lectin-like receptor NKG2D. As part of this receptor complex, this protein may activate phosphatidylinositol 3-kinase dependent signaling pathways through its intracytoplasmic YxxM motif. This receptor complex may have a role in cell survival and proliferation by activation of NK and T cell responses. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in bone marrow (RPKM 39.5), spleen (RPKM 20.3) and 12 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HCST in Genome Data Viewer
    Location:
    19q13.12
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (35902529..35904377)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (38448294..38450142)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (36393431..36395279)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904705 Neighboring gene RNA, 7SL, cytoplasmic 402, pseudogene Neighboring gene NFKB inhibitor delta Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:36389157-36389729 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:36389730-36390301 Neighboring gene H3K27ac hESC enhancers GRCh37_chr19:36390314-36390870 and GRCh37_chr19:36390871-36391426 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:36398209-36398362 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14505 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14507 Neighboring gene transmembrane immune signaling adaptor TYROBP Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14509 Neighboring gene leucine rich repeat and fibronectin type III domain containing 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Garrity D, et al. Proc Natl Acad Sci U S A, 2005 May 24. PMID 15894612, Free PMC Article
    2. Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors. André P, et al. Eur J Immunol, 2004 Apr. PMID 15048706
    3. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. Wu J, et al. J Exp Med, 2000 Oct 2. PMID 11015446, Free PMC Article
    4. CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer. Qi X, et al. Technol Cancer Res Treat, 2020 Jan-Dec. PMID 33153411, Free PMC Article
    5. The traffic of the NKG2D/Dap10 receptor complex during natural killer (NK) cell activation. Roda-Navarro P, et al. J Biol Chem, 2009 Jun 12. PMID 19329438, Free PMC Article

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer.
      Title: CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer.
    2. NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity.
      Title: NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity.
    3. These results suggest that NKG2D-DAP10 endocytosis represents a means to decrease cell surface receptor abundance, as well as to control signaling outcome in cytotoxic lymphocytes.
      Title: Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells.
    4. findings indicate that the functional interaction between RAGE and DAP10 coordinately regulates S100A8/A9-mediated survival and/or apoptotic response of keratinocytes
      Title: DNAX-activating protein 10 (DAP10) membrane adaptor associates with receptor for advanced glycation end products (RAGE) and modulates the RAGE-triggered signaling pathway in human keratinocytes.
    5. TGF-beta1 may reduce the expression of NKG2D/DAP10 and 2B4/SAPin patients with hepatitis B.
      Title: TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence.
    6. HMBOX1 negatively regulates the expression of NKG2D and the activation of the NKG2D/DAP10 signaling pathway in NK cells.
      Title: HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway.
    7. Other gamma(c) cytokines act similarly to IL-2 in up-regulating DAP10 expression and NKG2D-DAP10 surface expression.
      Title: Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the γc cytokines and TGF-β1.
    8. TGF-BETA1 down-modulates surface NKG2D expression by controlling the transcriptional and translational levels of DAP10.
      Title: A possible mechanism of impaired NK cytotoxicity in cancer patients: down-regulation of DAP10 by TGF-beta1.
    9. A transgenic mouse model demonstrates that induction of tolerance in Ly49H-positive natural killer (NK) cells by chronic exposure to virus-encoded ligand m157 requires signaling through the Ly49H adaptor protein DAP12, not the DAP10 adaptor protein.
      Title: Activation receptor-induced tolerance of mature NK cells in vivo requires signaling through the receptor and is reversible.
    10. the rapid degradation of NKG2D/DAP10 observed coincident with recruitment of the receptor to the cytotoxic immune synapse may explain the loss of NKG2D receptor expression after chronic exposure to NKG2D ligands
      Title: The traffic of the NKG2D/Dap10 receptor complex during natural killer (NK) cell activation.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of HCST PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZP586C1522

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables phosphatidylinositol 3-kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphatidylinositol 3-kinase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-macromolecule adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables signaling receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in regulation of immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    hematopoietic cell signal transducer
    Names
    DNAX-activation protein 10
    kinase assoc pro of ~10kDa
    kinase assoc protein
    membrane protein DAP10
    phosphoinositide-3-kinase adaptor protein
    transmembrane adapter protein KAP10

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001007469.2 → NP_001007470.1  hematopoietic cell signal transducer isoform 2 precursor

      See identical proteins and their annotated locations for NP_001007470.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2).
      Source sequence(s)
      AF072844, AL050163
      Consensus CDS
      CCDS46057.1
      UniProtKB/Swiss-Prot
      Q9UBK5
      Related
      ENSP00000400516.1, ENST00000437550.2
      Conserved Domains (1) summary
      pfam07213
      Location:1 → 92
      DAP10; DAP10 membrane protein

    2. NM_014266.4 → NP_055081.1  hematopoietic cell signal transducer isoform 1 precursor

      See identical proteins and their annotated locations for NP_055081.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AD000864, AL050163
      Consensus CDS
      CCDS32998.1
      UniProtKB/Swiss-Prot
      Q9UBK5, Q9UBS1, Q9Y3Y0
      Related
      ENSP00000246551.3, ENST00000246551.9
      Conserved Domains (1) summary
      pfam07213
      Location:1 → 93
      DAP10; DAP10 membrane protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      35902529..35904377
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017026193.2 → XP_016881682.1  hematopoietic cell signal transducer isoform X1

    2. XM_047438090.1 → XP_047294046.1  hematopoietic cell signal transducer isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      38448294..38450142
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054319594.1 → XP_054175569.1  hematopoietic cell signal transducer isoform X1

    2. XM_054319595.1 → XP_054175570.1  hematopoietic cell signal transducer isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UBK5.1 GenPept UniProtKB/Swiss-Prot:Q9UBK5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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