Names & Taxonomy

Uniprot ID:
Q13882
Entry Name:
PTK6_HUMAN
Status:
reviewed
Protein Names:
Protein-tyrosine kinase 6 (EC 2.7.10.2) (Breast tumor kinase) (Tyrosine-protein kinase BRK)
Gene Names:
PTK6 BRK
Gene Names Primary:
PTK6
Organism:
Homo sapiens (Human)

Structure

Length:
451
Sequence:
MVSRDQAHLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQGYVPHNYLAERETVESEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPCRKHEPEPLPHWDDWERPREEFTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMKKLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALSRGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQRPCFKALRERLSSFTSYENPT
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm. Nucleus. Cell projection, ruffle. Membrane

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=83 uM for ATP
Enzyme Regulation:
ENZYME REGULATION: Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity.
Active Site:
ACT_SITE 312 312 Proton acceptor.
Cross Reference Drug Bank:
DB05294
Gene Ontology Go:
cytoplasm
extrinsic component of cytoplasmic side of plasma membrane
nucleoplasm
nucleus
ruffle
ATP binding
identical protein binding
non-membrane spanning protein tyrosine kinase activity
receptor binding
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
Gene Ontology Biological Process:
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
Gene Ontology Molecular Function:
ATP binding
identical protein binding
non-membrane spanning protein tyrosine kinase activity
receptor binding
Gene Ontology Cellular Component:
cytoplasm
extrinsic component of cytoplasmic side of plasma membrane
nucleoplasm
nucleus
ruffle
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell projection
Complete proteome
Cytoplasm
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
Interacts With:
Itself; Q5JST6; P04626; Q8IW24; O14526; Q13480; Q5VWX1; P10721; Q04864; P23246; O00401

Publication

PubMed ID:
8036022 9333026 9749526 14702039 11780052 15489334 8940083 9185712 10980601 10913193 12121988 12833144 15471878 15572663 15509496 15539407 15961400 16179349 15870689 16651629 16568091 17822667 17997837 18829532 18296648 18691976 18719096 19439179 20193745 20026641 21479203 15056653 17344846