HCK

HCK
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
Aliases	HCK, JTK9, p59Hck, p61Hck, HCK proto-oncogene, Src family tyrosine kinase
External IDs	OMIM: 142370; MGI: 96052; HomoloGene: 20489; GeneCards: HCK; OMA:HCK - orthologs
Gene location (Human)
Chr.	Chromosome 20 (human)
End	32,101,856 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	152,993,361 bp
RNA expression pattern
	Top expressed in
	monocyte; ; granulocyte; ; blood; ; spleen; ; bone marrow; ; appendix; ; trabecular bone; ; middle frontal gyrus; ; bone marrow cells; ; periodontal fiber;
	Top expressed in
	granulocyte; ; stroma of bone marrow; ; tibiofemoral joint; ; spleen; ; blood; ; rib; ; mesenteric lymph nodes; ; right lung lobe; ; transitional epithelium of urinary bladder; ; left lung;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transferase activity; nucleotide binding; protein kinase activity; non-membrane spanning protein tyrosine kinase activity; kinase activity; protein binding; signaling receptor binding; ATP binding; protein tyrosine kinase activity; phosphotyrosine residue binding;
Cellular component	cytoplasm; cytosol; Golgi apparatus; cell projection; membrane; focal adhesion; extrinsic component of cytoplasmic side of plasma membrane; transport vesicle; cell junction; actin filament; caveola; lysosome; cytoskeleton; cytoplasmic vesicle; nucleus; nucleoplasm; plasma membrane;
Biological process	cell differentiation; leukocyte migration involved in immune response; positive regulation of actin filament polymerization; Fc-gamma receptor signaling pathway involved in phagocytosis; phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; cytokine-mediated signaling pathway; interferon-gamma-mediated signaling pathway; immune system process; leukocyte degranulation; negative regulation of apoptotic process; mitigation of host defenses by virus; protein phosphorylation; cell adhesion; respiratory burst after phagocytosis; regulation of DNA-binding transcription factor activity; positive regulation of cell population proliferation; regulation of inflammatory response; regulation of cell shape; regulation of podosome assembly; peptidyl-tyrosine autophosphorylation; phagocytosis; integrin-mediated signaling pathway; protein autophosphorylation; peptidyl-tyrosine phosphorylation; regulation of phagocytosis; mesoderm development; inflammatory response; innate immune response-activating signal transduction; positive regulation of actin cytoskeleton reorganization; lipopolysaccharide-mediated signaling pathway; exocytosis; viral process; innate immune response;
	Sources:Amigo / QuickGO
Orthologs
	3055
	15162
	ENSG00000101336
	ENSMUSG00000003283
	P08631
	P08103
NM_002110; NM_001172129; NM_001172130; NM_001172131; NM_001172132;
	NM_001172133
	NM_001172117; NM_010407
NP_001165600; NP_001165601; NP_001165602; NP_001165603; NP_001165604;
	NP_002101
	NP_001165588; NP_034537
	Wikidata
View/Edit Human	View/Edit Mouse

Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.^[5]

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. HCK and the Src family kinases have also been implicated in driving cell survival in drug-tolerant cancer cells. ^[6] 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.^[7]

Interactions

HCK has been shown to interact with:

ADAM15^[8]
BCR gene,^[9]^[10]
Cbl gene,^[11]^[12]
ELMO1,^[13]
Granulocyte colony-stimulating factor receptor,^[14]
RAPGEF1,^[15]
RAS p21 protein activator 1,^[16] and
RASA3.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000101336 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000003283 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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. doi:10.1128/mcb.7.6.2267. PMC 365351. PMID 3496523.
^ Saha T, Mondal J, Khiste S, Lusic H, Hu ZW, Jayabalan R, Hodgetts KJ, Jang H, Sengupta S, Lee SE, Park Y, Lee LP, Goldman A (2021-06-24). "Nanotherapeutic approaches to overcome distinct drug resistance barriers in models of breast cancer". Nanophotonics. 10 (12): 3063–3073. Bibcode:2021Nanop..10..142S. doi:10.1515/nanoph-2021-0142. PMC 8478290. PMID 34589378.
^ "Entrez Gene: HCK hemopoietic cell kinase".
^ 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". Journal of Biological Chemistry. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.
^ 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. S2CID 8695384.
^ 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.
^ 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. S2CID 34296309.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.

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. S2CID 33749514.
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. doi:10.1016/S0021-9258(19)39684-X. 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. doi:10.1128/mcb.11.9.4363. 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. doi:10.1128/mcb.7.6.2276. 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. doi:10.1002/j.1460-2075.1995.tb00183.x. 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. (Submitted manuscript). 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. doi:10.1128/mcb.15.7.3507. 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. doi:10.1002/j.1460-2075.1995.tb07024.x. 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. Bibcode:1994PNAS...91.8152C. 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000101336 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000003283 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid3496523-5] 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. doi:10.1128/mcb.7.6.2267. PMC 365351. PMID 3496523.

[:1-6] Saha T, Mondal J, Khiste S, Lusic H, Hu ZW, Jayabalan R, Hodgetts KJ, Jang H, Sengupta S, Lee SE, Park Y, Lee LP, Goldman A (2021-06-24). "Nanotherapeutic approaches to overcome distinct drug resistance barriers in models of breast cancer". Nanophotonics. 10 (12): 3063–3073. Bibcode:2021Nanop..10..142S. doi:10.1515/nanoph-2021-0142. PMC 8478290. PMID 34589378.

[7] "Entrez Gene: HCK hemopoietic cell kinase".

[pmid11741929-8] 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". Journal of Biological Chemistry. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID 11741929.

[pmid12592324-9] 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. S2CID 8695384.

[pmid10849448-10] 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.

[pmid11896602-11] 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. S2CID 34296309.

[pmid10092522-12] 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.

[pmid12029088-13] 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.

[pmid9790917-14] 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.

[pmid14551197-15] 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.

[pmid7782336-16] 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Function

Interactions

References

Further reading