HCK

HCK proto-oncogene, Src family tyrosine kinase
PDB rendering based on 1ad5.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1AD5​, 1BU1​, 1QCF​, 2C0I​, 2C0O​, 2C0T​, 2HCK​, 2HK5​, 2OI3​, 2OJ2​, 3HCK​, 3NHN​, 3RBB​, 3REA​, 3REB​, 3VRY​, 3VRZ​, 3VS0​, 3VS1​, 3VS2​, 3VS3​, 3VS4​, 3VS5​, 3VS6​, 3VS7​, 4HCK​, 4LUD​, 4LUE​, 4ORZ​, 4U5W​, 5HCK​
Identifiers
Symbols	HCK ; JTK9; p59Hck; p61Hck
External IDs	OMIM: 142370 MGI: 96052 HomoloGene: 20489 ChEMBL: 3234 GeneCards: HCK Gene
EC number	2.7.10.2
Gene ontology Molecular function • protein tyrosine kinase activity • non-membrane spanning protein tyrosine kinase activity • receptor binding • protein binding • ATP binding Cellular component • nucleus • lysosome • Golgi apparatus • cytosol • actin filament • caveola • focal adhesion • transport vesicle • extrinsic component of cytoplasmic side of plasma membrane • cell projection Biological process • leukocyte migration involved in immune response • innate immune response-activating signal transduction • protein phosphorylation • inflammatory response • cell adhesion • transmembrane receptor protein tyrosine kinase signaling pathway • integrin-mediated signaling pathway • mesoderm development • positive regulation of cell proliferation • regulation of cell shape • viral process • peptidyl-tyrosine phosphorylation • cytokine-mediated signaling pathway • cell differentiation • positive regulation of actin filament polymerization • lipopolysaccharide-mediated signaling pathway • peptidyl-tyrosine autophosphorylation • Fc-gamma receptor signaling pathway involved in phagocytosis • negative regulation of apoptotic process • leukocyte degranulation • innate immune response • respiratory burst after phagocytosis • protein autophosphorylation • regulation of defense response to virus by virus • regulation of inflammatory response • regulation of phagocytosis • regulation of sequence-specific DNA binding transcription factor activity • interferon-gamma-mediated signaling pathway • cellular response to peptide hormone stimulus • regulation of podosome assembly • positive regulation of actin cytoskeleton reorganization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3055	15162
Ensembl	ENSG00000101336	ENSMUSG00000003283
UniProt	P08631	P08103
RefSeq (mRNA)	NM_001172129	NM_001172117
RefSeq (protein)	NP_001165600	NP_001165588
Location (UCSC)	Chr 20: 32.05 – 32.1 Mb	Chr 2: 153.11 – 153.15 Mb
PubMed search

Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.^[1]

Function

The protein encoded by this gene is a protein-tyrosine kinase that is predominantly expressed in hemopoietic cell types, and belongs to the Src family of tyrosine kinases. The encoded protein may help couple the Fc receptor to the activation of the respiratory burst. In addition, it may play a role in neutrophil migration and in the degranulation of neutrophils. Alternate translation initiation site usage, including a non-AUG (CUG) codon, results in the production of two different isoforms, that have different subcellular localization.^[2]

Interactions

HCK has been shown to interact with:

• ADAM15^[3]
• BCR gene,^[4][5]
• Cbl gene,^[6][7]
• ELMO1,^[8]
• Granulocyte colony-stimulating factor receptor,^[9]
• RAPGEF1,^[10]
• RAS p21 protein activator 1,^[11] and
• RASA3.^[11]

References

1. Quintrell N, Lebo R, Varmus H, Bishop JM, Pettenati MJ, Le Beau MM, Diaz MO, Rowley JD (August 1987). "Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells". Mol Cell Biol 7 (6): 2267–75. PMC 365351. PMID 3496523.
2. "Entrez Gene: HCK hemopoietic cell kinase".
3. Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR (Feb 2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". The Journal of Biological Chemistry 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.
4. Stanglmaier M, Warmuth M, Kleinlein I, Reis S, Hallek M (Feb 2003). "The interaction of the Bcr-Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains". Leukemia 17 (2): 283–9. doi:10.1038/sj.leu.2402778. PMID 12592324.
5. Lionberger JM, Wilson MB, Smithgall TE (Jun 2000). "Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck". The Journal of Biological Chemistry 275 (24): 18581–5. doi:10.1074/jbc.C000126200. PMID 10849448.
6. Howlett CJ, Robbins SM (Mar 2002). "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation". Oncogene 21 (11): 1707–16. doi:10.1038/sj.onc.1205228. PMID 11896602.
7. Howlett CJ, Bisson SA, Resek ME, Tigley AW, Robbins SM (Apr 1999). "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase". Biochemical and Biophysical Research Communications 257 (1): 129–38. doi:10.1006/bbrc.1999.0427. PMID 10092522.
8. Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT (Aug 2002). "Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1". The Journal of Biological Chemistry 277 (31): 28238–46. doi:10.1074/jbc.M202783200. PMID 12029088.
9. Ward AC, Monkhouse JL, Csar XF, Touw IP, Bello PA (Oct 1998). "The Src-like tyrosine kinase Hck is activated by granulocyte colony-stimulating factor (G-CSF) and docks to the activated G-CSF receptor". Biochemical and Biophysical Research Communications 251 (1): 117–23. doi:10.1006/bbrc.1998.9441. PMID 9790917.
10. Shivakrupa R, Radha V, Sudhakar C, Swarup G (Dec 2003). "Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain". The Journal of Biological Chemistry 278 (52): 52188–94. doi:10.1074/jbc.M310656200. PMID 14551197.
11. Briggs SD, Bryant SS, Jove R, Sanderson SD, Smithgall TE (Jun 1995). "The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck". The Journal of Biological Chemistry 270 (24): 14718–24. doi:10.1074/jbc.270.24.14718. PMID 7782336.

Further reading

• Geyer M, Fackler OT, Peterlin BM (2001). "Structure--function relationships in HIV-1 Nef.". EMBO Rep. 2 (7): 580–5. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
• Lake JA, Carr J, Feng F, Mundy L, Burrell C, Li P (2003). "The role of Vif during HIV-1 infection: interaction with novel host cellular factors.". J. Clin. Virol. 26 (2): 143–52. doi:10.1016/S1386-6532(02)00113-0. PMID 12600646.
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication.". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410.
• Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (2004). "HIV/SIV escape from immune surveillance: focus on Nef.". Curr. HIV Res. 2 (2): 141–51. doi:10.2174/1570162043484924. PMID 15078178.
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects.". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Lichtenberg U, Quintrell N, Bishop JM (1992). "Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region.". Oncogene 7 (5): 849–58. PMID 1373873.
• Hradetzky D, Strebhardt K, Rübsamen-Waigmann H (1992). "The genomic locus of the human hemopoietic-specific cell protein tyrosine kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron structure among human PTKs of the src family.". Gene 113 (2): 275–80. doi:10.1016/0378-1119(92)90407-G. PMID 1572549.
• Kim JW, Sim SS, Kim UH, Nishibe S, Wahl MI, Carpenter G, Rhee SG (1990). "Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro.". J. Biol. Chem. 265 (7): 3940–3. PMID 1689310.
• Holtrich U, Bräuninger A, Strebhardt K, Rübsamen-Waigmann H (1992). "Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase.". Proc. Natl. Acad. Sci. U.S.A. 88 (23): 10411–5. doi:10.1073/pnas.88.23.10411. PMC 52938. PMID 1720539.
• Lock P, Ralph S, Stanley E, Boulet I, Ramsay R, Dunn AR (1991). "Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization.". Mol. Cell. Biol. 11 (9): 4363–70. PMC 361298. PMID 1875927.
• Ziegler SF, Marth JD, Lewis DB, Perlmutter RM (1987). "Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin.". Mol. Cell. Biol. 7 (6): 2276–85. PMC 365352. PMID 3453117.
• Lee CH, Leung B, Lemmon MA, Zheng J, Cowburn D, Kuriyan J, Saksela K (1995). "A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein.". EMBO J. 14 (20): 5006–15. PMC 394604. PMID 7588629.
• Liao F, Shin HS, Rhee SG (1993). "In vitro tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2 by src-family protein tyrosine kinases.". Biochem. Biophys. Res. Commun. 191 (3): 1028–33. doi:10.1006/bbrc.1993.1320. PMID 7682059.
• Briggs SD, Bryant SS, Jove R, Sanderson SD, Smithgall TE (1995). "The Ras GTPase-activating protein (GAP) is an SH3 domain-binding protein and substrate for the Src-related tyrosine kinase, Hck.". J. Biol. Chem. 270 (24): 14718–24. doi:10.1074/jbc.270.24.14718. PMID 7782336.
• Robbins SM, Quintrell NA, Bishop JM (1995). "Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae.". Mol. Cell. Biol. 15 (7): 3507–15. PMC 230587. PMID 7791757.
• Saksela K, Cheng G, Baltimore D (1995). "Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4.". EMBO J. 14 (3): 484–91. PMC 398106. PMID 7859737.
• Cheng G, Ye ZS, Baltimore D (1994). "Binding of Bruton's tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction.". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 8152–5. doi:10.1073/pnas.91.17.8152. PMC 44563. PMID 8058772.
• Wang AV, Scholl PR, Geha RS (1994). "Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn.". J. Exp. Med. 180 (3): 1165–70. doi:10.1084/jem.180.3.1165. PMC 2191633. PMID 8064233.