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 ... See more...

Aliases for HCST Gene

Aliases for HCST Gene

  • Hematopoietic Cell Signal Transducer 2 3 4 5
  • DNAX-Activation Protein 10 2 3 4
  • DAP10 2 3 4
  • KAP10 2 3 4
  • Phosphoinositide-3-Kinase Adaptor Protein 2 3
  • Transmembrane Adapter Protein KAP10 3 4
  • Kinase Assoc Pro Of ~10kDa 2 3
  • Membrane Protein DAP10 3 4
  • PIK3AP 3 4
  • Kinase Assoc Protein 3
  • DKFZP586C1522 2
  • HCST 5

External Ids for HCST Gene

Previous HGNC Symbols for HCST Gene

  • PIK3AP

Previous GeneCards Identifiers for HCST Gene

  • GC00U912965
  • GC19P041085
  • GC19P036393
  • GC19P032898
  • GC19P035981
  • GC19P037060
  • GC19P037232
  • GC19P037301
  • GC19P037735
  • GC19P036002
  • GC19P036029
  • GC19P036181
  • GC19P036259
  • GC19P036426
  • GC19P036587
  • GC19P036753
  • GC19P036900

Summaries for HCST Gene

Entrez Gene Summary for HCST Gene

  • 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]

GeneCards Summary for HCST Gene

HCST (Hematopoietic Cell Signal Transducer) is a Protein Coding gene. Diseases associated with HCST include Polycystic Lipomembranous Osteodysplasia With Sclerosing Leukoencephalopathy 1. Among its related pathways are Immune response Role of DAP12 receptors in NK cells and Innate Immune System. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and phosphatidylinositol 3-kinase binding.

UniProtKB/Swiss-Prot Summary for HCST Gene

  • 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 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.

Gene Wiki entry for HCST Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HCST Gene

Genomics for HCST Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HCST Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HCST on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HCST

Top Transcription factor binding sites by QIAGEN in the HCST gene promoter:
  • AML1a
  • c-Ets-1
  • C/EBPalpha
  • E47
  • Gfi-1
  • HSF1 (long)
  • HSF1short
  • Pax-4a
  • SEF-1 (1)
  • Tal-1

Genomic Locations for HCST Gene

Genomic Locations for HCST Gene
chr19:35,902,365-35,904,377
(GRCh38/hg38)
Size:
2,013 bases
Orientation:
Plus strand
chr19:36,393,382-36,395,279
(GRCh37/hg19)
Size:
1,898 bases
Orientation:
Plus strand

Genomic View for HCST Gene

Genes around HCST on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCST Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCST Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCST Gene

Proteins for HCST Gene

  • Protein details for HCST Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBK5-HCST_HUMAN
    Recommended name:
    Hematopoietic cell signal transducer
    Protein Accession:
    Q9UBK5
    Secondary Accessions:
    • Q9UBS1
    • Q9Y3Y0

    Protein attributes for HCST Gene

    Size:
    93 amino acids
    Molecular mass:
    9489 Da
    Quaternary structure:
    • Interacts with CLEC5A (By similarity). Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP (By similarity). Homodimer; Disulfide-linked. Heterohexamer composed of four subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via transmembrane domain) with KLRK1 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell-mediated cytotoxicity. Interacts with PIK3R1 and GRB2. Interacts with CD300H (PubMed:26221034).
    Miscellaneous:
    • Silencing of HCST suppresses cytolytic activity of T-cells and NK cells.

    Alternative splice isoforms for HCST Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HCST Gene

Post-translational modifications for HCST Gene

Other Protein References for HCST Gene

No data available for DME Specific Peptides for HCST Gene

Domains & Families for HCST Gene

Gene Families for HCST Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for HCST Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HCST Gene

GenScript: Design optimal peptide antigens:
  • Transmembrane adapter protein KAP10 (HCST_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UBK5

UniProtKB/Swiss-Prot:

HCST_HUMAN :
  • Belongs to the DAP10 family.
Family:
  • Belongs to the DAP10 family.
genes like me logo Genes that share domains with HCST: view

Function for HCST Gene

Molecular function for HCST Gene

UniProtKB/Swiss-Prot 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 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.
UniProtKB/Swiss-Prot Induction:
By T-cell receptor (TCR) ligation, which leads to enhanced KLRK1-HCST cell surface expression. Down-regulated by IL21/interleukin-21 in T-cells and NK cells.

Gene Ontology (GO) - Molecular Function for HCST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IBA,IPI 15294961
GO:0005515 protein binding IPI 10426994
GO:0043548 phosphatidylinositol 3-kinase binding IDA 10426994
genes like me logo Genes that share ontologies with HCST: view
genes like me logo Genes that share phenotypes with HCST: view

Animal Models for HCST Gene

MGI Knock Outs for HCST:
  • Hcst Hcst<tm1.1Cln>
  • Hcst Hcst<tm1.1Dnax>
  • Hcst Hcst<tm1Cln>

Animal Model Products

CRISPR Products

miRNA for HCST Gene

miRTarBase miRNAs that target HCST

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCST

Clone Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HCST Gene

Localization for HCST Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCST Gene

Membrane. Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCST gene
Compartment Confidence
plasma membrane 4
extracellular 4
lysosome 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Centriolar satellite (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HCST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0009986 cell surface IDA 10426994
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with HCST: view

Pathways & Interactions for HCST Gene

genes like me logo Genes that share pathways with HCST: view

Pathways by source for HCST Gene

Gene Ontology (GO) - Biological Process for HCST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IGI 10528161
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling IDA 10426994
GO:0050776 regulation of immune response TAS --
genes like me logo Genes that share ontologies with HCST: view

No data available for SIGNOR curated interactions for HCST Gene

Drugs & Compounds for HCST Gene

(2) Drugs for HCST Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Nutra 6556

(1) Additional Compounds for HCST Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HCST: view

Transcripts for HCST Gene

mRNA/cDNA for HCST Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCST

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HCST Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4
SP1:
SP2:

Relevant External Links for HCST Gene

GeneLoc Exon Structure for
HCST

Expression for HCST Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HCST Gene

mRNA differential expression in normal tissues according to GTEx for HCST Gene

This gene is overexpressed in Whole Blood (x22.8) and Spleen (x4.8).

Protein differential expression in normal tissues from HIPED for HCST Gene

This gene is overexpressed in CD8 Tcells (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HCST Gene



Protein tissue co-expression partners for HCST Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HCST

SOURCE GeneReport for Unigene cluster for HCST Gene:

Hs.117339

mRNA Expression by UniProt/SwissProt for HCST Gene:

Q9UBK5-HCST_HUMAN
Tissue specificity: Predominantly expressed in hemopoietic cells such as NK cells, subset of T-cells and monocytes. Detected in leukocytes, spleen, and thymus.

Evidence on tissue expression from TISSUES for HCST Gene

  • Lung(4.4)
  • Pancreas(4.2)
  • Spleen(3)
  • Bone marrow(3)
  • Lymph node(2.8)
  • Intestine(2.6)
  • Blood(2.5)
  • Liver(2)
genes like me logo Genes that share expression patterns with HCST: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HCST Gene

Orthologs for HCST Gene

This gene was present in the common ancestor of mammals.

Orthologs for HCST Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HCST 30 31
  • 98.57 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HCST 30 31
  • 84.39 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Hcst 30 17 31
  • 80 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hcst 30
  • 77.78 (n)
Dog
(Canis familiaris)
Mammalia HCST 31
  • 51 (a)
OneToOne
Species where no ortholog for HCST was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for HCST Gene

ENSEMBL:
Gene Tree for HCST (if available)
TreeFam:
Gene Tree for HCST (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HCST: view image

Paralogs for HCST Gene

No data available for Paralogs for HCST Gene

Variants for HCST Gene

Additional dbSNP identifiers (rs#s) for HCST Gene

Structural Variations from Database of Genomic Variants (DGV) for HCST Gene

Variant ID Type Subtype PubMed ID
dgv51n68 CNV loss 17160897

Variation tolerance for HCST Gene

Residual Variation Intolerance Score: 67% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.65; 13.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HCST Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCST

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HCST Gene

Disorders for HCST Gene

MalaCards: The human disease database

(1) MalaCards diseases for HCST Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search HCST in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HCST

genes like me logo Genes that share disorders with HCST: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HCST Gene

Publications for HCST Gene

  1. A Structural basis for the association of DAP12 with mouse, but not human, NKG2D. (PMID: 15294961) Rosen DB … Lanier LL (Journal of immunology (Baltimore, Md. : 1950) 2004) 3 4 23
  2. Molecular cloning and characterization of pig immunoreceptor DAP10 and NKG2D. (PMID: 11398969) Yim D … Kim YB (Immunogenetics 2001) 3 4 23
  3. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. (PMID: 11015446) Wu J … Lanier LL (The Journal of experimental medicine 2000) 3 4 23
  4. An activating immunoreceptor complex formed by NKG2D and DAP10. (PMID: 10426994) Wu J … Phillips JH (Science (New York, N.Y.) 1999) 2 3 4
  5. Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family. (PMID: 26221034) Niizuma K … Shibuya A (The Journal of biological chemistry 2015) 3 4

Products for HCST Gene

Sources for HCST Gene