Q9QUJ0 · HCST_MOUSE
- ProteinHematopoietic cell signal transducer
- GeneHcst
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | membrane | |
Molecular Function | phosphatidylinositol 3-kinase binding | |
Molecular Function | signaling receptor binding | |
Biological Process | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | regulation of immune response |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHematopoietic cell signal transducer
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9QUJ0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 18-35 | Extracellular | ||||
Sequence: SQTSAGSCSGCGTLSLPL | ||||||
Transmembrane | 36-56 | Helical | ||||
Sequence: LAGLVAADAVMSLLIVGVVFV | ||||||
Topological domain | 57-79 | Cytoplasmic | ||||
Sequence: CMRPHGRPAQEDGRVYINMPGRG |
Keywords
- Cellular component
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.
PTM/Processing
Features
Showing features for signal, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-17 | |||||
Sequence: MDPPGYLLFLLLLPVAA | ||||||
Chain | PRO_0000330290 | 18-79 | Hematopoietic cell signal transducer | |||
Sequence: SQTSAGSCSGCGTLSLPLLAGLVAADAVMSLLIVGVVFVCMRPHGRPAQEDGRVYINMPGRG | ||||||
Modified residue | 72 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated; PIK3R1 and GRB2 associate specifically with tyrosine-phosphorylated HCST.
O-glycosylated.
Keywords
- PTM
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).
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9QUJ0 | Clec5a Q9R007 | 3 | EBI-15761243, EBI-15761206 | |
BINARY | Q9QUJ0 | Tyrobp O54885 | 4 | EBI-15761243, EBI-15687058 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 72-74 | GRB2 binding site | ||||
Sequence: YIN | ||||||
Region | 72-75 | PIK3R1 binding site | ||||
Sequence: YINM |
Sequence similarities
Belongs to the DAP10 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe 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.
- Name1
- Length79
- Mass (Da)8,114
- Last updated2000-05-01 v1
- ChecksumB411985277D601E3
Q9QUJ0-2
- Name2
- Differences from canonical
- 15-22: Missing
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_033023 | 15-22 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |