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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:63,528,001-63,537,376)mRNA (may differ from genome)Protein (451 aa)
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PTK6_HUMAN
DESCRIPTION: RecName: Full=Protein-tyrosine kinase 6; EC=2.7.10.2; 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;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PTK6
Diseases sorted by gene-association score: breast cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 69.26 RPKM in Esophagus - Mucosa
Total median expression: 280.20 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.8062-0.416 Picture PostScript Text
3' UTR -562.801535-0.367 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR000980 - SH2
IPR001452 - SH3_domain
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom

Pfam Domains:
PF07714 - Protein tyrosine kinase
PF00017 - SH2 domain
PF00018 - SH3 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1RJA - NMR MuPIT 2KGT - NMR MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0042802 identical protein binding

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

Cellular Component:
GO:0001726 ruffle
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016604 nuclear body
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  X78549 - H.sapiens brk mRNA for tyrosine kinase.
JD341771 - Sequence 322795 from Patent EP1572962.
JD106600 - Sequence 87624 from Patent EP1572962.
JD243171 - Sequence 224195 from Patent EP1572962.
JD243170 - Sequence 224194 from Patent EP1572962.
JD136111 - Sequence 117135 from Patent EP1572962.
JD378254 - Sequence 359278 from Patent EP1572962.
JD478261 - Sequence 459285 from Patent EP1572962.
JD052754 - Sequence 33778 from Patent EP1572962.
JD217478 - Sequence 198502 from Patent EP1572962.
AK124082 - Homo sapiens cDNA FLJ42088 fis, clone TESOP2000801, moderately similar to PROTO-ONCOGENE TYROSINE-PROTEIN KINASE YES (EC 2.7.1.112).
BC035843 - Homo sapiens PTK6 protein tyrosine kinase 6, mRNA (cDNA clone MGC:46149 IMAGE:5746034), complete cds.
JD116390 - Sequence 97414 from Patent EP1572962.
JD062002 - Sequence 43026 from Patent EP1572962.
JD429732 - Sequence 410756 from Patent EP1572962.
JD477643 - Sequence 458667 from Patent EP1572962.
JD566199 - Sequence 547223 from Patent EP1572962.
JD256282 - Sequence 237306 from Patent EP1572962.
JD303419 - Sequence 284443 from Patent EP1572962.
JD498303 - Sequence 479327 from Patent EP1572962.
JD383073 - Sequence 364097 from Patent EP1572962.
JD514608 - Sequence 495632 from Patent EP1572962.
JD294740 - Sequence 275764 from Patent EP1572962.
JD165603 - Sequence 146627 from Patent EP1572962.
JD233064 - Sequence 214088 from Patent EP1572962.
AK301364 - Homo sapiens cDNA FLJ57625 complete cds, highly similar to Tyrosine-protein kinase 6 (EC 2.7.10.2).
JD493967 - Sequence 474991 from Patent EP1572962.
JD241124 - Sequence 222148 from Patent EP1572962.
JD077342 - Sequence 58366 from Patent EP1572962.
JD472991 - Sequence 454015 from Patent EP1572962.
JD199390 - Sequence 180414 from Patent EP1572962.
AK315232 - Homo sapiens cDNA, FLJ96231, Homo sapiens PTK6 protein tyrosine kinase 6 (PTK6), mRNA.
AB527573 - Synthetic construct DNA, clone: pF1KB6658, Homo sapiens PTK6 gene for PTK6 protein tyrosine kinase 6, without stop codon, in Flexi system.
AK301691 - Homo sapiens cDNA FLJ56703 complete cds, highly similar to Tyrosine-protein kinase 6 (EC 2.7.10.2).

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q13882 (Reactome details) participates in the following event(s):

R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK)
R-HSA-8857565 Phosphorylated GPNMB recruits PTK6 and LRRK2 in the presence of LINC01139
R-HSA-8849435 PTPN1 dephosphorylates PTK6
R-HSA-8848023 Activated PTK6 binds STAP2
R-HSA-8848110 SOCS3 binds activated PTK6
R-HSA-8848414 Activated PTK6 binds CDKN1B
R-HSA-8848596 PTK6 binds PXN
R-HSA-8848713 PTK6 binds BCAR1
R-HSA-8848751 PTK6 binds AKT1
R-HSA-8848774 PTK6 binds DOK1
R-HSA-8848864 PTK6 binds ARAP1
R-HSA-8848930 PTK6 translocates to the nucleus
R-HSA-8849055 PTK6 binds ARHGAP35
R-HSA-8849102 SRMS phosphorylates PTK6
R-HSA-8849428 PTPN1 binds PTK6
R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation
R-HSA-8848436 PTK6 phosphorylates CDKN1B
R-HSA-8848606 PTK6 phosphorylates PXN
R-HSA-8848726 PTK6 phosphorylates BCAR1
R-HSA-8848776 PTK6 phosphorylates DOK1
R-HSA-8848873 PTK6 phosphorylates ARAP1
R-HSA-8849068 PTK6 phosphorylates ARHGAP35
R-HSA-8848939 PTK6 binds KHDRBS1
R-HSA-8848975 PTK6 phosphorylates KHDRBS1
R-HSA-8857577 LINC01139 facilitates PTK6 autophosphorylation
R-HSA-8848077 PTK6 phosphorylates STAP2
R-HSA-8848087 STAP2 recruits STAT3 to PTK6
R-HSA-8848124 PTK6 phosphorylates STAT3
R-HSA-8848758 PTK6 phosphorylates AKT1
R-HSA-8848818 PTK6 phosphorylates CBL
R-HSA-8849032 PTK6 phosphorylates KHDRBS2
R-HSA-8849042 PTK6 phosphorylates KHDRBS3
R-HSA-8849463 PTK6 phosphorylates SFPQ
R-HSA-8942607 Tyrosine kinases phosphorylate Cip/Kip inhibitors bound to CDK4/6:CCND complexes
R-HSA-8857583 LINC01139 promotes phosphorylation of HIF1A by PTK6 and LRRK2
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8857538 PTK6 promotes HIF1A stabilization
R-HSA-8849473 PTK6 Expression
R-HSA-8849472 PTK6 Down-Regulation
R-HSA-8849474 PTK6 Activates STAT3
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-8849470 PTK6 Regulates Cell Cycle
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8849469 PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
R-HSA-8849468 PTK6 Regulates Proteins Involved in RNA Processing
R-HSA-1227986 Signaling by ERBB2
R-HSA-8848021 Signaling by PTK6
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-69231 Cyclin D associated events in G1
R-HSA-69206 G1/S Transition
R-HSA-69242 S Phase
R-HSA-162582 Signal Transduction
R-HSA-69236 G1 Phase
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: B2RCR3, B4DW46, BRK, ENST00000542869.1, ENST00000542869.2, NM_005975, PTK6_HUMAN, Q13882, Q58F01, uc002yfg.1, uc002yfg.2, uc002yfg.3, uc002yfg.4, uc002yfg.5, uc002yfg.6
UCSC ID: ENST00000542869.3
RefSeq Accession: NM_005975
Protein: Q13882 (aka PTK6_HUMAN)
CCDS: CCDS13524.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.