UniProtKB - Q13882 (PTK6_HUMAN)
(max 400 entries)x
Your basket is currently empty. i
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
Protein-tyrosine kinase 6
Gene
PTK6
Organism
Homo sapiens (Human)
Status
Functioni
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.1 Publication
Catalytic activityi
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation3 Publications
Enzyme regulationi
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.5 Publications
Kineticsi
- KM=83 µM for ATP1 Publication
- Vmax=37 nmol/min/mg enzyme1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 219 | ATPPROSITE-ProRule annotation2 Publications | 1 | |
Active sitei | 312 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 197 – 205 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
- protein tyrosine kinase activity Source: Reactome
- receptor binding Source: GO_Central
GO - Biological processi
- cell migration Source: UniProtKB
- cellular response to retinoic acid Source: BHF-UCL
- ERBB2 signaling pathway Source: Reactome
- innate immune response Source: GO_Central
- intestinal epithelial cell differentiation Source: Ensembl
- negative regulation of growth Source: Ensembl
- negative regulation of protein tyrosine kinase activity Source: UniProtKB
- negative regulation of signal transduction Source: Reactome
- peptidyl-tyrosine autophosphorylation Source: GO_Central
- positive regulation of cell cycle Source: Reactome
- positive regulation of epidermal growth factor receptor signaling pathway Source: Reactome
- positive regulation of neuron projection development Source: BHF-UCL
- positive regulation of tyrosine phosphorylation of STAT protein Source: Reactome
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: ProtInc
- regulation of cell proliferation Source: GO_Central
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- tyrosine phosphorylation of STAT protein Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2. 2681. |
Reactomei | R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21. R-HSA-69231. Cyclin D associated events in G1. R-HSA-8847993. ERBB2 Activates PTK6 Signaling. R-HSA-8849468. PTK6 Regulates Proteins Involved in RNA Processing. R-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1. R-HSA-8849470. PTK6 Regulates Cell Cycle. R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases. R-HSA-8849472. PTK6 Down-Regulation. R-HSA-8849473. PTK6 Expression. R-HSA-8849474. PTK6 Activates STAT3. R-HSA-8857538. PTK6 promotes HIF1A stabilization. |
SignaLinki | Q13882. |
SIGNORi | Q13882. |
Names & Taxonomyi
Protein namesi | Recommended name: Protein-tyrosine kinase 6 (EC:2.7.10.23 Publications)Alternative name(s): Breast tumor kinase Tyrosine-protein kinase BRK |
Gene namesi | Name:PTK6 Synonyms:BRK |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000101213.6. |
HGNCi | HGNC:9617. PTK6. |
MIMi | 602004. gene. |
neXtProti | NX_Q13882. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 44 | W → A: Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region. 2 Publications | 1 | |
Mutagenesisi | 66 | Y → A: Decrease in STAP2 phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 105 | R → L: Decrease in STAP2 phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 184 | W → A: Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1. 1 Publication | 1 | |
Mutagenesisi | 219 | K → M: Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. 3 Publications | 1 | |
Mutagenesisi | 219 | K → R: Abolishes kinase activity. 1 Publication | 1 | |
Mutagenesisi | 342 | Y → A: 3-fold lower specific kinase activity. Decreased, but still significant, autophosphorylation. Decreased, but still significant, autophosphorylation; when associated with A-447. 1 Publication | 1 | |
Mutagenesisi | 447 | Y → F: Decrease in transforming potential and increase in the kinase activity level. Decreased, but still significant, autophosphorylation; when associated with A-342. 3 Publications | 1 |
Organism-specific databases
DisGeNETi | 5753. |
OpenTargetsi | ENSG00000101213. |
PharmGKBi | PA33960. |
Chemistry databases
ChEMBLi | CHEMBL4601. |
DrugBanki | DB05294. Vandetanib. |
GuidetoPHARMACOLOGYi | 2182. |
Polymorphism and mutation databases
BioMutai | PTK6. |
DMDMi | 8928302. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000088133 | 1 – 451 | Protein-tyrosine kinase 6Add BLAST | 451 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 13 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 61 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 66 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 114 | Phosphotyrosine; by autocatalysisCombined sources1 Publication | 1 | |
Modified residuei | 342 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 351 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 447 | Phosphotyrosine1 Publication | 1 |
Post-translational modificationi
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.4 Publications
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | Q13882. |
PaxDbi | Q13882. |
PeptideAtlasi | Q13882. |
PRIDEi | Q13882. |
PTM databases
iPTMneti | Q13882. |
PhosphoSitePlusi | Q13882. |
Expressioni
Tissue specificityi
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.4 Publications
Gene expression databases
Bgeei | ENSG00000101213. |
CleanExi | HS_PTK6. |
Genevisiblei | Q13882. HS. |
Organism-specific databases
HPAi | CAB032952. HPA036070. HPA036071. |
Interactioni
Subunit structurei
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.By similarity10 Publications
Binary interactionsi
GO - Molecular functioni
- identical protein binding Source: IntAct
- receptor binding Source: GO_Central
Protein-protein interaction databases
BioGridi | 111720. 26 interactors. |
DIPi | DIP-39785N. |
IntActi | Q13882. 29 interactors. |
MINTi | Q13882. |
STRINGi | 9606.ENSP00000217185. |
Chemistry databases
BindingDBi | Q13882. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 12 – 14 | Combined sources | 3 | |
Beta strandi | 35 – 40 | Combined sources | 6 | |
Beta strandi | 45 – 50 | Combined sources | 6 | |
Beta strandi | 56 – 62 | Combined sources | 7 | |
Turni | 64 – 66 | Combined sources | 3 | |
Beta strandi | 67 – 70 | Combined sources | 4 | |
Helixi | 85 – 92 | Combined sources | 8 | |
Beta strandi | 102 – 106 | Combined sources | 5 | |
Beta strandi | 108 – 112 | Combined sources | 5 | |
Beta strandi | 114 – 118 | Combined sources | 5 | |
Beta strandi | 125 – 131 | Combined sources | 7 | |
Beta strandi | 133 – 135 | Combined sources | 3 | |
Beta strandi | 137 – 140 | Combined sources | 4 | |
Beta strandi | 143 – 147 | Combined sources | 5 | |
Helixi | 148 – 157 | Combined sources | 10 | |
Beta strandi | 162 – 164 | Combined sources | 3 | |
Helixi | 188 – 190 | Combined sources | 3 | |
Beta strandi | 191 – 200 | Combined sources | 10 | |
Beta strandi | 203 – 210 | Combined sources | 8 | |
Turni | 211 – 213 | Combined sources | 3 | |
Beta strandi | 214 – 221 | Combined sources | 8 | |
Helixi | 223 – 225 | Combined sources | 3 | |
Helixi | 233 – 240 | Combined sources | 8 | |
Beta strandi | 250 – 254 | Combined sources | 5 | |
Beta strandi | 256 – 264 | Combined sources | 9 | |
Helixi | 272 – 277 | Combined sources | 6 | |
Turni | 281 – 283 | Combined sources | 3 | |
Helixi | 286 – 305 | Combined sources | 20 | |
Helixi | 315 – 317 | Combined sources | 3 | |
Beta strandi | 318 – 320 | Combined sources | 3 | |
Helixi | 322 – 324 | Combined sources | 3 | |
Beta strandi | 326 – 328 | Combined sources | 3 | |
Helixi | 333 – 336 | Combined sources | 4 | |
Helixi | 339 – 343 | Combined sources | 5 | |
Helixi | 345 – 348 | Combined sources | 4 | |
Helixi | 349 – 352 | Combined sources | 4 | |
Helixi | 356 – 361 | Combined sources | 6 | |
Helixi | 366 – 380 | Combined sources | 15 | |
Turni | 381 – 384 | Combined sources | 4 | |
Helixi | 393 – 401 | Combined sources | 9 | |
Helixi | 414 – 423 | Combined sources | 10 | |
Helixi | 428 – 430 | Combined sources | 3 | |
Helixi | 434 – 442 | Combined sources | 9 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1RJA | NMR | - | A | 75-174 | [»] | |
2KGT | NMR | - | A | 1-72 | [»] | |
5D7V | X-ray | 2.33 | A/B/C/D | 185-446 | [»] | |
5DA3 | X-ray | 1.70 | A | 185-446 | [»] | |
5H2U | X-ray | 2.24 | A/B/C/D | 185-446 | [»] | |
ProteinModelPortali | Q13882. | |||||
SMRi | Q13882. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13882. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 8 – 72 | SH3PROSITE-ProRule annotationAdd BLAST | 65 | |
Domaini | 78 – 170 | SH2PROSITE-ProRule annotationAdd BLAST | 93 | |
Domaini | 191 – 445 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 255 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 171 – 190 | LinkerAdd BLAST | 20 |
Domaini
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 similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily.PROSITE-ProRule annotation
Keywords - Domaini
SH2 domain, SH3 domainPhylogenomic databases
eggNOGi | KOG0197. Eukaryota. COG0515. LUCA. |
GeneTreei | ENSGT00760000118938. |
HOGENOMi | HOG000233858. |
HOVERGENi | HBG008761. |
InParanoidi | Q13882. |
KOi | K08894. |
OMAi | VRHYKIW. |
OrthoDBi | EOG091G0596. |
PhylomeDBi | Q13882. |
TreeFami | TF351634. |
Family and domain databases
CDDi | cd10358. SH2_PTK6_Brk. 1 hit. |
Gene3Di | 3.30.505.10. 1 hit. |
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR035846. PTK6_SH2. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR036860. SH2_dom_sf. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. |
Pfami | View protein in Pfam PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. |
PRINTSi | PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE. |
SMARTi | View protein in SMART SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. |
SUPFAMi | SSF50044. SSF50044. 1 hit. SSF55550. SSF55550. 1 hit. SSF56112. SSF56112. 1 hit. |
PROSITEi | View protein in PROSITE PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. PS50002. SH3. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q13882-1) [UniParc]FASTAAdd to basket
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.
10 20 30 40 50
MVSRDQAHLG PKYVGLWDFK SRTDEELSFR AGDVFHVARK EEQWWWATLL
60 70 80 90 100
DEAGGAVAQG YVPHNYLAER ETVESEPWFF GCISRSEAVR RLQAEGNATG
110 120 130 140 150
AFLIRVSEKP SADYVLSVRD TQAVRHYKIW RRAGGRLHLN EAVSFLSLPE
160 170 180 190 200
LVNYHRAQSL SHGLRLAAPC RKHEPEPLPH WDDWERPREE FTLCRKLGSG
210 220 230 240 250
YFGEVFEGLW KDRVQVAIKV ISRDNLLHQQ MLQSEIQAMK KLRHKHILAL
260 270 280 290 300
YAVVSVGDPV YIITELMAKG SLLELLRDSD EKVLPVSELL DIAWQVAEGM
310 320 330 340 350
CYLESQNYIH RDLAARNILV GENTLCKVGD FGLARLIKED VYLSHDHNIP
360 370 380 390 400
YKWTAPEALS RGHYSTKSDV WSFGILLHEM FSRGQVPYPG MSNHEAFLRV
410 420 430 440 450
DAGYRMPCPL ECPPSVHKLM LTCWCRDPEQ RPCFKALRER LSSFTSYENP
T
Sequence cautioni
The sequence BAG62908 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_041760 | 16 | L → F in a renal papillary sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_041761 | 436 | A → T1 PublicationCorresponds to variant dbSNP:rs56145017Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042066 | 78 – 134 | WFFGC…WRRAG → AGHAGCAALQDLAACRGPAA PERGGVLPQPARACELPQGP EPVPRPAAGRALPEARA in isoform 2. 2 PublicationsAdd BLAST | 57 | |
Alternative sequenceiVSP_042067 | 135 – 451 | Missing in isoform 2. 2 PublicationsAdd BLAST | 317 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X78549 mRNA. Translation: CAA55295.1. U61412 U61411 Genomic DNA. Translation: AAC34935.1. AK315232 mRNA. Translation: BAG37660.1. AK301364 mRNA. Translation: BAG62908.1. Sequence problems. AL121829 Genomic DNA. No translation available. BC035843 mRNA. Translation: AAH35843.1. |
CCDSi | CCDS13524.1. [Q13882-1] CCDS74750.1. [Q13882-2] |
PIRi | S49016. |
RefSeqi | NP_001243287.1. NM_001256358.1. [Q13882-2] NP_005966.1. NM_005975.3. [Q13882-1] |
UniGenei | Hs.51133. |
Genome annotation databases
Ensembli | ENST00000217185; ENSP00000217185; ENSG00000101213. [Q13882-2] ENST00000542869; ENSP00000442460; ENSG00000101213. [Q13882-1] |
GeneIDi | 5753. |
KEGGi | hsa:5753. |
UCSCi | uc002yfg.5. human. [Q13882-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | PTK6_HUMAN | |
Accessioni | Q13882Primary (citable) accession number: Q13882 Secondary accession number(s): B2RCR3, B4DW46, Q58F01 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | November 1, 1996 | |
Last modified: | March 28, 2018 | |
This is version 188 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |