InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HCK

Summary

InnateDB Protein

IDBP-476978.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HCK

Protein Name

hemopoietic cell kinase

Synonyms

JTK9; p59Hck; p61Hck;

Species

Homo sapiens

Ensembl Protein

ENSP00000429848

InnateDB Gene

IDBG-64463 (HCK)

Protein Structure

UniProt Annotation

Function

Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269PubMed:10092522, ECO:0000269PubMed:10779760, ECO:0000269PubMed:10973280, ECO:0000269PubMed:11741929, ECO:0000269PubMed:11896602, ECO:0000269PubMed:12411494, ECO:0000269PubMed:15010462, ECO:0000269PubMed:15952790, ECO:0000269PubMed:15998323, ECO:0000269PubMed:17310994, ECO:0000269PubMed:17535448, ECO:0000269PubMed:19114024, ECO:0000269PubMed:19903482, ECO:0000269PubMed:20452982, ECO:0000269PubMed:21338576, ECO:0000269PubMed:7535819, ECO:0000269PubMed:8132624, ECO:0000269PubMed:9406996, ECO:0000269PubMed:9407116}.

Subcellular Localization

Isoform 1: Lysosome. Membrane; Lipid-anchor. Cell projection, podosome membrane; Lipid-anchor. Cytoplasm, cytosol. Note=Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, some of this fraction is myristoylated.Isoform 2: Cell membrane {ECO:0000269PubMed:11904303}; Lipid-anchor {ECO:0000269PubMed:11904303}. Membrane, caveola {ECO:0000269PubMed:11904303}; Lipid-anchor {ECO:0000269PubMed:11904303}. Cell junction, focal adhesion {ECO:0000269PubMed:11904303}. Cytoplasm, cytoskeleton {ECO:0000269PubMed:11904303}. Golgi apparatus {ECO:0000269PubMed:11904303}. Cytoplasmic vesicle {ECO:0000269PubMed:11904303}. Lysosome {ECO:0000269PubMed:11904303}. Nucleus {ECO:0000269PubMed:11904303}. Note=20% of this isoform is associated with caveolae. Localization at the cell membrane and at caveolae requires palmitoylation at Cys-3. Colocalizes with the actin cytoskeleton at focal adhesions.Cytoplasmic vesicle, secretory vesicle. Cytoplasm, cytosol.

Disease Associations

Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.

Tissue Specificity

Detected in monocytes and neutrophils (at protein level). Expressed predominantly in cells of the myeloid and B-lymphoid lineages. Highly expressed in granulocytes. Detected in tonsil. {ECO:0000269PubMed:3453117, ECO:0000269PubMed:8064233, ECO:0000269PubMed:8995234}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 73 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	73 [view]
Protein-Protein	72 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0002522	leukocyte migration involved in immune response
GO:0002758	innate immune response-activating signal transduction
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007155	cell adhesion
GO:0007229	integrin-mediated signaling pathway
GO:0007498	mesoderm development
GO:0008284	positive regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0016032	viral process
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0030838	positive regulation of actin filament polymerization
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043066	negative regulation of apoptotic process
GO:0043299	leukocyte degranulation
GO:0045087	innate immune response
GO:0045728	respiratory burst after phagocytosis
GO:0046777	protein autophosphorylation
GO:0050690	regulation of defense response to virus by virus
GO:0050727	regulation of inflammatory response
GO:0050764	regulation of phagocytosis
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0060333	interferon-gamma-mediated signaling pathway
GO:0071801	regulation of podosome assembly
GO:2000251	positive regulation of actin cytoskeleton reorganization

Cellular Component

GO:0005634	nucleus
GO:0005764	lysosome
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005884	actin filament
GO:0005901	caveola
GO:0005925	focal adhesion
GO:0030133	transport vesicle
GO:0031234	extrinsic component of cytoplasmic side of plasma membrane
GO:0042995	cell projection

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM