Q13882 · PTK6_HUMAN
- ProteinProtein-tyrosine kinase 6
- GenePTK6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids451 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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.
Miscellaneous
The inhibitors bind to the ATP-binding pocket.
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Activity 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.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
83 μM | ATP |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
37 nmol/min/mg |
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein-tyrosine kinase 6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13882
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041760 | 16 | in a renal papillary sample; somatic mutation | |||
Sequence: L → F | ||||||
Mutagenesis | 44 | Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region. | ||||
Sequence: W → A | ||||||
Mutagenesis | 66 | Decrease in STAP2 phosphorylation. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 105 | Decrease in STAP2 phosphorylation. | ||||
Sequence: R → L | ||||||
Mutagenesis | 184 | Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1. | ||||
Sequence: W → A | ||||||
Mutagenesis | 219 | Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. | ||||
Sequence: K → M | ||||||
Mutagenesis | 219 | Abolishes kinase activity. | ||||
Sequence: K → R | ||||||
Mutagenesis | 342 | 3-fold lower specific kinase activity. Decreased, but still significant, autophosphorylation. Decreased, but still significant, autophosphorylation; when associated with A-447. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_041761 | 436 | in dbSNP:rs56145017 | |||
Sequence: A → T | ||||||
Mutagenesis | 447 | Decrease in transforming potential and increase in the kinase activity level. Decreased, but still significant, autophosphorylation; when associated with A-342. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 559 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000088133 | 1-451 | UniProt | Protein-tyrosine kinase 6 | |||
Sequence: MVSRDQAHLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQGYVPHNYLAERETVESEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPCRKHEPEPLPHWDDWERPREEFTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMKKLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALSRGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQRPCFKALRERLSSFTSYENPT | |||||||
Modified residue | 13 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 61 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 66 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue | 114 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 114 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 342 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 342 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 351 | UniProt | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 443 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 446 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 447 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 447 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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 percentage 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.
Gene expression databases
Organism-specific databases
Interaction
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
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
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-72 | SH3 | ||||
Sequence: HLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQGYVPHNYLAERET | ||||||
Domain | 78-170 | SH2 | ||||
Sequence: WFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPC | ||||||
Region | 171-190 | Linker | ||||
Sequence: RKHEPEPLPHWDDWERPREE | ||||||
Domain | 191-445 | Protein kinase | ||||
Sequence: FTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMKKLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALSRGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQRPCFKALRERLSSFT |
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.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q13882-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length451
- Mass (Da)51,834
- Last updated1996-11-01 v1
- ChecksumCDCAC0EE242E1BD7
Q13882-2
- Name2
- SynonymsALT-PTK6, LambdaM5
Sequence caution
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X78549 EMBL· GenBank· DDBJ | CAA55295.1 EMBL· GenBank· DDBJ | mRNA | ||
U61412 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61406 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61407 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61408 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61409 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61410 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U61411 EMBL· GenBank· DDBJ | AAC34935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK315232 EMBL· GenBank· DDBJ | BAG37660.1 EMBL· GenBank· DDBJ | mRNA | ||
AK301364 EMBL· GenBank· DDBJ | BAG62908.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AL121829 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC035843 EMBL· GenBank· DDBJ | AAH35843.1 EMBL· GenBank· DDBJ | mRNA |