HCK
Domain
The SH3 domain mediates binding to HIV-1 Nef.
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.
Involvement in disease
Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.
Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.
Autoinflammation with pulmonary and cutaneous vasculitis
AIPCV
An autosomal dominant disorder characterized by cutaneous vasculitis and chronic pulmonary inflammation that evolves to fibrosis. AIPCV manifests soon after birth with petechial skin lesions, followed by progressive pulmonary involvement causing restrictive lung disease and respiratory insufficiency.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion protein mediates activation of HCK. Phosphorylation at Tyr-411 increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-522, suggesting that this site is a target of other kinases.
Ubiquitinated by CBL, leading to its degradation via the proteasome.
Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
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.
Cellular localization
- Isoform 1
- Lysosome
- Membrane
- Lipid-anchor
- Cell projection
- Podosome membrane
- Lipid-anchor
- Cytoplasm
- Cytosol
- 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
- Lipid-anchor
- Membrane
- Caveola
- Lipid-anchor
- Cell junction
- Focal adhesion
- Cytoplasm
- Cytoskeleton
- Golgi apparatus
- Cytoplasmic vesicle
- Lysosome
- Nucleus
- 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
Alternative names
Tyrosine-protein kinase HCK, Hematopoietic cell kinase, Hemopoietic cell kinase, p59-HCK/p60-HCK, p59Hck, p61Hck, HCK