PTK6

Protein tyrosine kinase 6
NMR structure of the SH2 domain of PTK6.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1RJA​, 2KGT​
Identifiers
Symbols	PTK6 ; BRK
External IDs	OMIM: 602004 MGI: 99683 HomoloGene: 68494 ChEMBL: 4601 GeneCards: PTK6 Gene
EC number	2.7.10.2
Gene ontology Molecular function • non-membrane spanning protein tyrosine kinase activity • receptor binding • protein binding • ATP binding • identical protein binding Cellular component • ruffle • nucleus • nucleoplasm • cytoplasm • extrinsic component of cytoplasmic side of plasma membrane Biological process • protein phosphorylation • transmembrane receptor protein tyrosine kinase signaling pathway • positive regulation of neuron projection development • cell migration • actin cytoskeleton organization • peptidyl-tyrosine autophosphorylation • regulation of cell proliferation • tyrosine phosphorylation of Stat3 protein • tyrosine phosphorylation of Stat5 protein • innate immune response • negative regulation of growth • protein autophosphorylation • intestinal epithelial cell differentiation • negative regulation of protein tyrosine kinase activity • cellular response to retinoic acid Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5753	20459
Ensembl	ENSG00000101213	ENSMUSG00000038751
UniProt	Q13882	Q64434
RefSeq (mRNA)	NM_001256358	NM_009184
RefSeq (protein)	NP_001243287	NP_033210
Location (UCSC)	Chr 20: 63.53 – 63.54 Mb	Chr 2: 181.19 – 181.2 Mb
PubMed search

Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene.^[2][3][4]

Function

Tyrosine-protein kinase 6 (also known as Breast Tumor Kinase, Brk) is a cytoplasmic non-receptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. The encoded protein has been shown to undergo autophosphorylation.^[4]

Clinical significance

Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue.^[4]

Interactions

PTK6 has been shown to interact with STAP2^[5] and KHDRBS1.^[6]

References

1. PDB: 1rja​; Hong E, Shin J, Kim HI, Lee ST, Lee W (July 2004). "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain". J. Biol. Chem. 279 (28): 29700–8. doi:10.1074/jbc.M313185200. PMID 15056653.
2. Lee ST, Strunk KM, Spritz RA (December 1993). "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes". Oncogene 8 (12): 3403–10. PMID 8247543.
3. Park SH, Lee KH, Kim H, Lee ST (September 1997). "Assignment of the human PTK6 gene encoding a non-receptor protein tyrosine kinase to 20q13.3 by fluorescence in situ hybridization". Cytogenet Cell Genet 77 (3–4): 271–2. doi:10.1159/000134595. PMID 9284935.
4. "Entrez Gene: PTK6 PTK6 protein tyrosine kinase 6".
5. Mitchell, P J; Sara E A; Crompton M R (August 2000). "A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK". Oncogene (ENGLAND) 19 (37): 4273–82. doi:10.1038/sj.onc.1203775. ISSN 0950-9232. PMID 10980601.
6. Derry, J J; Richard S; Valderrama Carvajal H; Ye X; Vasioukhin V; Cochrane A W; Chen T; Tyner A L (August 2000). "Sik (BRK) Phosphorylates Sam68 in the Nucleus and Negatively Regulates Its RNA Binding Ability". Mol. Cell. Biol. (UNITED STATES) 20 (16): 6114–26. doi:10.1128/MCB.20.16.6114-6126.2000. ISSN 0270-7306. PMC 86087. PMID 10913193.

Further reading

• Serfas MS, Tyner AL (2003). "Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases". Oncol. Res. 13 (6–10): 409–19. PMID 12725532.
• Mitchell PJ, Barker KT, Martindale JE, et al. (1994). "Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours". Oncogene 9 (8): 2383–90. PMID 8036022.
• Kamalati T, Jolin HE, Mitchell PJ, et al. (1997). "Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor". J. Biol. Chem. 271 (48): 30956–63. doi:10.1074/jbc.271.48.30956. PMID 8940083.
• Lee H, Kim M, Lee KH, et al. (1998). "Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase". Mol. Cells 8 (4): 401–7. PMID 9749526.
• Llor X, Serfas MS, Bie W, et al. (1999). "BRK/Sik expression in the gastrointestinal tract and in colon tumors". Clin. Cancer Res. 5 (7): 1767–77. PMID 10430081.
• Derry JJ, Richard S, Valderrama Carvajal H, et al. (2000). "Sik (BRK) Phosphorylates Sam68 in the Nucleus and Negatively Regulates Its RNA Binding Ability". Mol. Cell. Biol. 20 (16): 6114–26. doi:10.1128/MCB.20.16.6114-6126.2000. PMC 86087. PMID 10913193.
• Mitchell PJ, Sara EA, Crompton MR (2000). "A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK". Oncogene 19 (37): 4273–82. doi:10.1038/sj.onc.1203775. PMID 10980601.
• Kamalati T, Jolin HE, Fry MJ, Crompton MR (2000). "Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation". Oncogene 19 (48): 5471–6. doi:10.1038/sj.onc.1203931. PMID 11114724.
• Hong E, Shin J, Bang E, et al. (2001). "Complete sequence-specific 1H, 13C and 15N resonance assignments of the human PTK6 SH2 domain". J. Biomol. NMR 19 (3): 291–2. doi:10.1023/A:1011221125013. PMID 11330822.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
• Kang KN, Kim M, Pae KM, Lee ST (2002). "Characterization of the 5'-flanking region of the human PTK6 gene". Biochim. Biophys. Acta 1574 (3): 365–9. doi:10.1016/s0167-4781(02)00234-8. PMID 11997104.
• Qiu H, Miller WT (2002). "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition". J. Biol. Chem. 277 (37): 34634–41. doi:10.1074/jbc.M203877200. PMID 12121988.
• Koo BK, Kim MH, Lee ST, Lee W (2002). "Purification and spectroscopic characterization of the human protein tyrosine kinase-6 SH3 domain". J. Biochem. Mol. Biol. 35 (3): 343–7. doi:10.5483/BMBRep.2002.35.3.343. PMID 12297019.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Coyle JH, Guzik BW, Bor YC, et al. (2003). "Sam68 Enhances the Cytoplasmic Utilization of Intron-Containing RNA and Is Functionally Regulated by the Nuclear Kinase Sik/BRK". Mol. Cell. Biol. 23 (1): 92–103. doi:10.1128/MCB.23.1.92-103.2003. PMC 140664. PMID 12482964.
• Derry JJ, Prins GS, Ray V, Tyner AL (2003). "Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells". Oncogene 22 (27): 4212–20. doi:10.1038/sj.onc.1206465. PMID 12833144.
• Qiu H, Miller WT (2004). "Role of the Brk SH3 domain in substrate recognition". Oncogene 23 (12): 2216–23. doi:10.1038/sj.onc.1207339. PMID 14676834.