Human Gene PTK6 (ENST00000542869.3) from GENCODE V44
Description: Homo sapiens protein tyrosine kinase 6 (PTK6), transcript variant 1, mRNA. (from RefSeq NM_005975) RefSeq Summary (NM_005975): The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. 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. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]. Gencode Transcript: ENST00000542869.3 Gencode Gene: ENSG00000101213.7 Transcript (Including UTRs) Position: hg38 chr20:63,528,001-63,537,376 Size: 9,376 Total Exon Count: 8 Strand: - Coding Region Position: hg38 chr20:63,529,536-63,537,314 Size: 7,779 Coding Exon Count: 8
ID:PTK6_HUMAN DESCRIPTION: RecName: Full=Protein-tyrosine kinase 6; EC=126.96.36.199; AltName: Full=Breast tumor kinase; AltName: Full=Tyrosine-protein kinase BRK; 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. FUNCTION: Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=83 uM for ATP; Vmax=37 nmol/min/mg enzyme; SUBUNIT: Interacts with GAP-A.p65 (By similarity). Interacts (via SH3 and SH2 domains) with KHDRBS1. Interacts (via SH3 and SH2 domains) with phosphorylated IRS4. Interacts with ADAM15. Interacts (via SH3 domain) with SFPQ. Interacts with EGFR and ERBB2. Interacts with STAP2. Interacts with PNX. Interacts with SFPQ. Interacts with PTK/ATK. Interacts with CTNNB1. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, ruffle. Membrane (By similarity). Note=Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate. TISSUE SPECIFICITY: Epithelia-specific. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues. Not expressed in breast or ovarian tissue but expressed in high pourcentage of breast and ovarian cancers. Also overexpressed in some metastatic melanomas, lymphomas, colon cancers, squamous cell carcinomas and prostate cancers. Also found in melanocytes. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 2 is present in prostate epithelial cell lines derived from normal prostate and prostate adenocarcinomas, as well as in a variety of cell lines. DOMAIN: The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein- protein interactions, but is likely more important for the regulation of catalytic activity. PTM: Autophosphorylated. Autophosphorylation of Tyr-342 leads to an increase of kinase activity. Tyr-447 binds to the SH2 domain when phosphorylated and negatively regulates kinase activity. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. SEQUENCE CAUTION: Sequence=BAG62908.1; Type=Erroneous translation; Note=Wrong choice of CDS;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13882
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007260 tyrosine phosphorylation of STAT protein GO:0009968 negative regulation of signal transduction GO:0010976 positive regulation of neuron projection development GO:0016310 phosphorylation GO:0016477 cell migration GO:0038083 peptidyl-tyrosine autophosphorylation GO:0038128 ERBB2 signaling pathway GO:0042127 regulation of cell proliferation GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0045087 innate immune response GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway GO:0045787 positive regulation of cell cycle GO:0045926 negative regulation of growth GO:0046777 protein autophosphorylation GO:0060575 intestinal epithelial cell differentiation GO:0061099 negative regulation of protein tyrosine kinase activity GO:0071300 cellular response to retinoic acid