Protein-tyrosine kinase 6

Details

Name
Protein-tyrosine kinase 6
Synonyms
  • 2.7.10.2
  • Breast tumor kinase
  • BRK
  • Tyrosine-protein kinase BRK
Gene Name
PTK6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008582|Protein-tyrosine kinase 6
MVSRDQAHLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQG
YVPHNYLAERETVESEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRD
TQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPCRKHEPEPLPH
WDDWERPREEFTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMK
KLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGM
CYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALS
RGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLM
LTCWCRDPEQRPCFKALRERLSSFTSYENPT
Number of residues
451
Molecular Weight
51833.72
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / identical protein binding / non-membrane spanning protein tyrosine kinase activity / receptor binding
Processes
actin cytoskeleton organization / cell migration / cellular response to retinoic acid / innate immune response / intestinal epithelial cell differentiation / negative regulation of growth / negative regulation of protein tyrosine kinase activity / peptidyl-tyrosine autophosphorylation / positive regulation of neuron projection development / protein autophosphorylation / protein phosphorylation / regulation of cell proliferation / transmembrane receptor protein tyrosine kinase signaling pathway / tyrosine phosphorylation of Stat3 protein / tyrosine phosphorylation of Stat5 protein
Components
cytoplasm / extrinsic component of cytoplasmic side of plasma membrane / nucleoplasm / nucleus / ruffle
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0013286|Protein-tyrosine kinase 6 (PTK6)
ATGGTGTCCCGGGACCAGGCTCACCTGGGCCCCAAGTATGTGGGCCTCTGGGACTTCAAG
TCCCGGACGGACGAGGAGCTGAGCTTCCGCGCGGGGGACGTCTTCCACGTGGCCAGGAAG
GAGGAGCAGTGGTGGTGGGCCACGCTGCTGGACGAGGCGGGTGGGGCCGTGGCCCAGGGC
TATGTGCCCCACAACTACCTGGCCGAGAGGGAGACGGTGGAGTCGGAACCTGCGGGACAC
GCAGGCTGTGCGGCACTACAAGATCTGGCGGCGTGCCGGGGGCCGGCTGCACCTGAACGA
GGCGGTGTCCTTCCTCAGCCTGCCCGAGCTTGTGAACTACCACAGGGCCCAGAGCCTGTC
CCACGGCCTGCGGCTGGCCGCGCCCTGCCGGAAGCACGAGCCTGA
Chromosome Location
20
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ13882
UniProtKB Entry NamePTK6_HUMAN
HGNC IDHGNC:9617
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05294VandetanibapprovedunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails
DB11800Tivozanibapproved, investigationalunknownDetails