Tyrosine-protein kinase HCK
Also known as: HCK
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.
Classification
- Family (Pfam)
- PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1
- InterPro
- HCK_SH2, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_AS, Tyr_kinase_cat_dom
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 40
- 1AD5 X-ray 2.60A
- 1BU1 X-ray 2.60A
- 1QCF X-ray 2.00A
- 2C0I X-ray 2.30A
- 2C0O X-ray 2.85A
- 2C0T X-ray 2.15A
- 2HCK X-ray 3.00A
- 2HK5 X-ray 2.00A
- 2OI3 NMR
- 2OJ2 NMR
- 3HCK NMR
- 3NHN X-ray 2.61A
- … and 28 more
A predicted model is available from AlphaFold.
Gene Ontology · 44
- GO:0005901 caveola
- GO:0042995 cell projection
- GO:0009898 cytoplasmic side of plasma membrane
- GO:0005856 cytoskeleton
- GO:0005829 cytosol
- GO:0005925 focal adhesion
- GO:0005794 Golgi apparatus
- GO:0005764 lysosome
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0030133 transport vesicle
- GO:0005524 ATP binding
- GO:0008289 lipid binding
- GO:0004715 non-membrane spanning protein tyrosine kinase activity
- GO:0001784 phosphotyrosine residue binding
- GO:0004713 protein tyrosine kinase activity
- GO:0005102 signaling receptor binding
- GO:0007155 cell adhesion
- GO:0030154 cell differentiation
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0019221 cytokine-mediated signaling pathway
- GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
- GO:0006954 inflammatory response
- GO:0002758 innate immune response-activating signaling pathway
- GO:0007229 integrin-mediated signaling pathway
- GO:0035556 intracellular signal transduction
- GO:0043299 leukocyte degranulation
- GO:0002522 leukocyte migration involved in immune response
- GO:0031663 lipopolysaccharide-mediated signaling pathway
- GO:0007498 mesoderm development
- GO:0043066 negative regulation of apoptotic process
- GO:0002862 negative regulation of inflammatory response to antigenic stimulus
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0030838 positive regulation of actin filament polymerization
- GO:0008284 positive regulation of cell population proliferation
- GO:0046777 protein autophosphorylation
- GO:0006468 protein phosphorylation
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0008360 regulation of cell shape
- GO:0050727 regulation of inflammatory response
- GO:0050764 regulation of phagocytosis
- GO:0071801 regulation of podosome assembly
- GO:0045728 respiratory burst after phagocytosis
- GO:0060333 type II interferon-mediated signaling pathway
Disease associations
- autoinflammation with pulmonary and cutaneous vasculitis MONDO:0957204
Drugs targeting this protein · 6
- DASATINIB ANHYDROUS inhibitor
- ILORASERTIB inhibitor
- BOSUTINIB inhibitor
- XL-228 inhibitor
- TG100-801 inhibitor
- ENMD-981693 inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Tyrosine-protein kinase HCK 0.99
- Tyrosine-protein kinase HCK 0.99
- Tyrosine-protein kinase HCK 0.98
- Proto-oncogene tyrosine-protein kinase LCK 0.96
- Proto-oncogene tyrosine-protein kinase LCK 0.96
- Proto-oncogene tyrosine-protein kinase LCK 0.96
- Proto-oncogene tyrosine-protein kinase LCK 0.96
- Tyrosine-protein kinase Lck 0.96
- Tyrosine-protein kinase Lyn 0.96
- Tyrosine-protein kinase Lck 0.96
- Tyrosine-protein kinase Lyn 0.95
- Tyrosine-protein kinase Lyn 0.95
Co-cited proteins · studied together in the literature
- Protein Nef 3 shared papers
- WD repeat and coiled-coil-containing protein 1 shared papers
- Disintegrin and metalloproteinase domain-containing protein 15 2 shared papers
- Tyrosine-protein kinase HCK 2 shared papers
- Low affinity immunoglobulin gamma Fc region receptor II-a 1 shared papers
- Engulfment and cell motility protein 1 1 shared papers
- Breakpoint cluster region protein 1 shared papers
- Signal transducer and activator of transcription 5B 1 shared papers
- GRB2-associated-binding protein 1 1 shared papers
- Interleukin-6 receptor subunit beta 1 shared papers
- Virion infectivity factor 1 shared papers
- E3 ubiquitin-protein ligase CBL 2 shared papers
Literature · 55 cited papers
- Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK. J. Allergy Clin. Immunol. · 2022
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma tyrosine kinase ALK. Biomed. Rep. · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef. PLoS ONE · 2011
- Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly. Traffic · 2011
- Protein tyrosine kinases in neutrophil activation and recruitment. Arch. Biochem. Biophys. · 2011
- Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism. J. Biol. Chem. · 2010
- Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner. J. Biol. Chem. · 2010
- c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration. FEBS Lett. · 2010
- Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. · 2009
- Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins. J. Cell. Biochem. · 2009
- … and 43 more in the literature graph