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

Summary

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

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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

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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

A006G29 (e-PCR)
- UniSTS:39994

D19S844E (e-PCR)
- UniSTS:153967

G32347 (e-PCR)
- UniSTS:116938

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)

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
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