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Protein

Hematopoietic cell signal transducer

Gene

HCST

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.10 Publications

Miscellaneous

Silencing of HCST suppresses cytolytic activity of T-cells and NK cells.

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • protein phosphorylation Source: CACAO
  • regulation of immune response Source: Reactome

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Names & Taxonomyi

Protein namesi
Recommended name:
Hematopoietic cell signal transducer
Alternative name(s):
DNAX-activation protein 10
Membrane protein DAP10
Transmembrane adapter protein KAP10
Gene namesi
Name:HCST
Synonyms:DAP10, KAP10, PIK3AP
ORF Names:UNQ587/PRO1157
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000126264.9
HGNCiHGNC:16977 HCST
MIMi604089 gene
neXtProtiNX_Q9UBK5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 48ExtracellularSequence analysisAdd BLAST30
Transmembranei49 – 69HelicalSequence analysisAdd BLAST21
Topological domaini70 – 93CytoplasmicSequence analysisAdd BLAST24

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi57D → A: Abolishes stable interaction with KLRK1. 1 Publication1
Mutagenesisi88N → Q: Abrogates cell killing and interaction with GRB2. No effect on interaction with PIK3R1. 1 Publication1
Mutagenesisi89M → Q: Abrogates cell killing and interaction with PIK3R1. No effect on interaction with GRB2. 1 Publication1

Organism-specific databases

DisGeNETi10870
OpenTargetsiENSG00000126264
PharmGKBiPA134956649

Polymorphism and mutation databases

BioMutaiHCST
DMDMi74734930

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000033028719 – 93Hematopoietic cell signal transducerAdd BLAST75

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei86Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylated; PIK3R1 and GRB2 associate specifically with tyrosine-phosphorylated HCST.3 Publications
O-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9UBK5
PeptideAtlasiQ9UBK5
PRIDEiQ9UBK5

PTM databases

iPTMnetiQ9UBK5
PhosphoSitePlusiQ9UBK5

Expressioni

Tissue specificityi

Predominantly expressed in hemopoietic cells such as NK cells, subset of T-cells and monocytes. Detected in leukocytes, spleen, and thymus.1 Publication

Inductioni

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.2 Publications

Gene expression databases

BgeeiENSG00000126264
CleanExiHS_HCST
GenevisibleiQ9UBK5 HS

Organism-specific databases

HPAiCAB034435
HPA063026

Interactioni

Subunit structurei

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.By similarity6 Publications

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116079, 3 interactors
CORUMiQ9UBK5
IntActiQ9UBK5, 2 interactors
STRINGi9606.ENSP00000246551

Structurei

3D structure databases

ProteinModelPortaliQ9UBK5
SMRiQ9UBK5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni86 – 89PIK3R1 binding site4
Regioni86 – 88GRB2 binding site3

Sequence similaritiesi

Belongs to the DAP10 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J782 Eukaryota
ENOG4111C1J LUCA
GeneTreeiENSGT00390000012777
HOGENOMiHOG000112856
HOVERGENiHBG106666
InParanoidiQ9UBK5
KOiK07988
OMAiKIYINMP
OrthoDBiEOG09370TG6
PhylomeDBiQ9UBK5
TreeFamiTF338335

Family and domain databases

InterProiView protein in InterPro
IPR009861 HCST
PANTHERiPTHR21409 PTHR21409, 1 hit
PfamiView protein in Pfam
PF07213 DAP10, 2 hits

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UBK5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MIHLGHILFL LLLPVAAAQT TPGERSSLPA FYPGTSGSCS GCGSLSLPLL
60 70 80 90
AGLVAADAVA SLLIVGAVFL CARPRRSPAQ EDGKVYINMP GRG
Length:93
Mass (Da):9,489
Last modified:May 1, 2000 - v1
Checksum:i97786F24F8A2EE44
GO
Isoform 2 (identifier: Q9UBK5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     81-81: Missing.

Show »
Length:92
Mass (Da):9,360
Checksum:i5D257437153A4FB4
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03302281Missing in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172929 mRNA Translation: AAD50293.1
AF072844 mRNA Translation: AAD46986.1
AF072845 Genomic DNA Translation: AAD46987.1
AF122904 mRNA Translation: AAD47911.1
AF285447 mRNA Translation: AAG29425.1
AY359058 mRNA Translation: AAQ89417.1
AL050163 mRNA Translation: CAB43303.2
BC035931 mRNA Translation: AAH35931.1
BC046348 mRNA Translation: AAH46348.1
BC065224 mRNA Translation: AAH65224.1
CCDSiCCDS32998.1 [Q9UBK5-1]
CCDS46057.1 [Q9UBK5-2]
PIRiT08788
RefSeqiNP_001007470.1, NM_001007469.1 [Q9UBK5-2]
NP_055081.1, NM_014266.3 [Q9UBK5-1]
UniGeneiHs.117339

Genome annotation databases

EnsembliENST00000246551; ENSP00000246551; ENSG00000126264 [Q9UBK5-1]
ENST00000437550; ENSP00000400516; ENSG00000126264 [Q9UBK5-2]
GeneIDi10870
KEGGihsa:10870
UCSCiuc002ock.2 human [Q9UBK5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHCST_HUMAN
AccessioniPrimary (citable) accession number: Q9UBK5
Secondary accession number(s): Q9UBS1, Q9Y3Y0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

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