Q64434
SS
Gene name |
Ptk6 (Sik) |
Protein name |
Protein-tyrosine kinase 6 |
Names |
EC 2.7.10.2 , SRC-related intestinal kinase |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:20459 |
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
Human PTK6 (also known as breast tumor kinase (Brk)) is a non-receptor protein-tyrosine kinase. 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. PTK6 is composed of SH3, SH2, and catalytic domains. The SH3 domain binds the proline-rich linker region between the SH2 domain and the catalytic domain. The disruption of the interaction enhances the oncogenic property of PTK6. In addition, mutation at SH2 domain of PTK6 resulted in higher catalytic activity. The site plays an important role in its negative regulation of the enzyme activity. Tyr(P) peptide derived from the C-terminal region of PTK6 including Tyr(P)-447 successfully bound to the SH2 domain, supporting the autoinhibitory role of PTK6 protein.
Autoinhibitory domains (AIDs)
Target domain |
171-191 (Linker region between the SH2 domain and the catalytic domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Hong E et al. (2004) "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain", The Journal of biological chemistry, 279, 29700-8
- Ko S et al. (2009) "Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6", Biochemical and biophysical research communications, 384, 236-42
- Qiu H et al. (2002) "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition", The Journal of biological chemistry, 277, 34634-41
Autoinhibited structure
Activated structure
1 structures for Q64434
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q64434-F1 | Predicted | AlphaFoldDB |
28 variants for Q64434
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3392450467 | 36 | H>L | No | EVA | |
| rs3392679958 | 37 | V>G | No | EVA | |
| rs3392662756 | 38 | T>N | No | EVA | |
| rs3392633417 | 39 | K>M | No | EVA | |
| rs3392450497 | 40 | K>E | No | EVA | |
| rs3388621194 | 67 | L>R | No | EVA | |
| rs3388621372 | 76 | E>G | No | EVA | |
| rs236335379 | 134 | E>* | No | EVA | |
| rs225430192 | 134 | E>A | No | EVA | |
| rs258692683 | 136 | R>Q | No | EVA | |
| rs243119845 | 147 | N>S | No | EVA | |
| rs252077467 | 215 | H>R | No | EVA | |
| rs3388604499 | 220 | V>M | No | EVA | |
| rs3388618977 | 225 | N>I | No | EVA | |
| rs3388622753 | 227 | L>P | No | EVA | |
| rs3388622716 | 243 | R>W | No | EVA | |
| rs3388617210 | 248 | L>M | No | EVA | |
| rs1134443262 | 264 | T>M | No | EVA | |
| rs3388621136 | 267 | M>K | No | EVA | |
| rs3388611405 | 280 | D>V | No | EVA | |
| rs3388623589 | 296 | V>A | No | EVA | |
| rs27693077 | 343 | L>F | No | EVA | |
| rs3388618951 | 361 | R>Q | No | EVA | |
| rs3388621359 | 375 | V>I | No | EVA | |
| rs3388613171 | 383 | R>K | No | EVA | |
| rs240962005 | 407 | P>L | No | EVA | |
| rs3388623586 | 428 | P>L | No | EVA | |
| rs215183312 | 447 | Y>* | No | EVA |
No associated diseases with Q64434
8 regional properties for Q64434
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 191 - 450 | IPR000719 |
| domain | SH2 domain | 76 - 170 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 192 - 441 | IPR001245 |
| domain | SH3 domain | 8 - 72 | IPR001452 |
| active_site | Tyrosine-protein kinase, active site | 308 - 320 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 197 - 219 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 191 - 441 | IPR020635 |
| domain | PTK6, SH2 domain | 75 - 174 | IPR035846 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.2 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| nuclear body | Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| ruffle | Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| identical protein binding | Binding to an identical protein or proteins. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction |
| signaling receptor binding | Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
10 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. |
| cellular response to retinoic acid | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a retinoic acid stimulus. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| intestinal epithelial cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a columnar/cuboidal epithelial cell of the intestine. |
| negative regulation of growth | Any process that stops, prevents or reduces the rate or extent of growth, the increase in size or mass of all or part of an organism. |
| positive regulation of neuron projection development | Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). |
| protein autophosphorylation | The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). |
| transmembrane receptor protein tyrosine kinase signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| tyrosine phosphorylation of STAT protein | The process of introducing a phosphate group to a tyrosine residue of a STAT (Signal Transducer and Activator of Transcription) protein. |
90 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A0JNB0 | FYN | Tyrosine-protein kinase Fyn | Bos taurus (Bovine) | SS |
| Q0VBZ0 | CSK | Tyrosine-protein kinase CSK | Bos taurus (Bovine) | SS |
| Q3ZC95 | BTK | Tyrosine-protein kinase | Bos taurus (Bovine) | EV SS |
| P42683 | LCK | Proto-oncogene tyrosine-protein kinase LCK | Gallus gallus (Chicken) | SS |
| P41239 | CSK | Tyrosine-protein kinase CSK | Gallus gallus (Chicken) | SS |
| P00523 | SRC | Proto-oncogene tyrosine-protein kinase Src | Gallus gallus (Chicken) | EV |
| Q02977 | YRK | Proto-oncogene tyrosine-protein kinase Yrk | Gallus gallus (Chicken) | SS |
| Q8JH64 | BTK | Tyrosine-protein kinase BTK | Gallus gallus (Chicken) | SS |
| P09324 | YES1 | Tyrosine-protein kinase Yes | Gallus gallus (Chicken) | SS |
| Q05876 | FYN | Tyrosine-protein kinase Fyn | Gallus gallus (Chicken) | SS |
| Q75R65 | JAK2 | Tyrosine-protein kinase JAK2 | Gallus gallus (Chicken) | SS |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| P41240 | CSK | Tyrosine-protein kinase CSK | Homo sapiens (Human) | SS |
| P51451 | BLK | Tyrosine-protein kinase Blk | Homo sapiens (Human) | SS |
| P06239 | LCK | Tyrosine-protein kinase Lck | Homo sapiens (Human) | EV |
| P23458 | JAK1 | Tyrosine-protein kinase JAK1 | Homo sapiens (Human) | SS |
| P06241 | FYN | Tyrosine-protein kinase Fyn | Homo sapiens (Human) | SS |
| P51813 | BMX | Cytoplasmic tyrosine-protein kinase BMX | Homo sapiens (Human) | SS |
| P12931 | SRC | Proto-oncogene tyrosine-protein kinase Src | Homo sapiens (Human) | EV |
| P09769 | FGR | Tyrosine-protein kinase Fgr | Homo sapiens (Human) | SS |
| P42680 | TEC | Tyrosine-protein kinase Tec | Homo sapiens (Human) | SS |
| O60674 | JAK2 | Tyrosine-protein kinase JAK2 | Homo sapiens (Human) | EV |
| P42679 | MATK | Megakaryocyte-associated tyrosine-protein kinase | Homo sapiens (Human) | SS |
| P52333 | JAK3 | Tyrosine-protein kinase JAK3 | Homo sapiens (Human) | SS |
| Q08881 | ITK | Tyrosine-protein kinase ITK/TSK | Homo sapiens (Human) | EV |
| P07948 | LYN | Tyrosine-protein kinase Lyn | Homo sapiens (Human) | SS |
| P29597 | TYK2 | Non-receptor tyrosine-protein kinase TYK2 | Homo sapiens (Human) | EV |
| P08631 | HCK | Tyrosine-protein kinase HCK | Homo sapiens (Human) | EV |
| P07947 | YES1 | Tyrosine-protein kinase Yes | Homo sapiens (Human) | SS |
| P42685 | FRK | Tyrosine-protein kinase FRK | Homo sapiens (Human) | EV |
| Q06187 | BTK | Tyrosine-protein kinase BTK | Homo sapiens (Human) | EV |
| Q13882 | PTK6 | Protein-tyrosine kinase 6 | Homo sapiens (Human) | EV |
| Q9R117 | Tyk2 | Non-receptor tyrosine-protein kinase TYK2 | Mus musculus (Mouse) | SS |
| Q62137 | Jak3 | Tyrosine-protein kinase JAK3 | Mus musculus (Mouse) | SS |
| Q62120 | Jak2 | Tyrosine-protein kinase JAK2 | Mus musculus (Mouse) | EV |
| P52332 | Jak1 | Tyrosine-protein kinase JAK1 | Mus musculus (Mouse) | SS |
| P05480 | Src | Proto-oncogene tyrosine-protein kinase Src | Mus musculus (Mouse) | EV |
| P06240 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Mus musculus (Mouse) | SS |
| P14234 | Fgr | Tyrosine-protein kinase Fgr | Mus musculus (Mouse) | SS |
| P16277 | Blk | Tyrosine-protein kinase Blk | Mus musculus (Mouse) | SS |
| P35991 | Btk | Tyrosine-protein kinase BTK | Mus musculus (Mouse) | EV |
| P41241 | Csk | Tyrosine-protein kinase CSK | Mus musculus (Mouse) | EV |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | Mus musculus (Mouse) | SS |
| Q922K9 | Frk | Tyrosine-protein kinase FRK | Mus musculus (Mouse) | SS |
| P48025 | Syk | Tyrosine-protein kinase SYK | Mus musculus (Mouse) | SS |
| P43404 | Zap70 | Tyrosine-protein kinase ZAP-70 | Mus musculus (Mouse) | SS |
| P25911 | Lyn | Tyrosine-protein kinase Lyn | Mus musculus (Mouse) | EV |
| P39688 | Fyn | Tyrosine-protein kinase Fyn | Mus musculus (Mouse) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | Mus musculus (Mouse) | SS |
| P24604 | Tec | Tyrosine-protein kinase Tec | Mus musculus (Mouse) | SS |
| P41242 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Mus musculus (Mouse) | SS |
| Q9QVP9 | Ptk2b | Protein-tyrosine kinase 2-beta | Mus musculus (Mouse) | PR |
| P34152 | Ptk2 | Focal adhesion kinase 1 | Mus musculus (Mouse) | SS |
| Q99ML2 | Tnk1 | Non-receptor tyrosine-protein kinase TNK1 | Mus musculus (Mouse) | PR |
| O54967 | Tnk2 | Activated CDC42 kinase 1 | Mus musculus (Mouse) | SS |
| P70451 | Fer | Tyrosine-protein kinase Fer | Mus musculus (Mouse) | PR |
| Q6J9G1 | Styk1 | Tyrosine-protein kinase STYK1 | Mus musculus (Mouse) | PR |
| P00520 | Abl1 | Tyrosine-protein kinase ABL1 | Mus musculus (Mouse) | EV |
| Q62270 | Srms | Tyrosine-protein kinase Srms | Mus musculus (Mouse) | SS |
| Q4JIM5 | Abl2 | Tyrosine-protein kinase ABL2 | Mus musculus (Mouse) | SS |
| A1Y2K1 | FYN | Tyrosine-protein kinase Fyn | Sus scrofa (Pig) | SS |
| O19064 | JAK2 | Tyrosine-protein kinase JAK2 | Sus scrofa (Pig) | SS |
| Q62662 | Frk | Tyrosine-protein kinase FRK | Rattus norvegicus (Rat) | SS |
| Q62844 | Fyn | Tyrosine-protein kinase Fyn | Rattus norvegicus (Rat) | SS |
| Q07014 | Lyn | Tyrosine-protein kinase Lyn | Rattus norvegicus (Rat) | SS |
| P50545 | Hck | Tyrosine-protein kinase HCK | Rattus norvegicus (Rat) | SS |
| Q9WUD9 | Src | Proto-oncogene tyrosine-protein kinase Src | Rattus norvegicus (Rat) | SS |
| Q01621 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Rattus norvegicus (Rat) | SS |
| Q6P6U0 | Fgr | Tyrosine-protein kinase Fgr | Rattus norvegicus (Rat) | SS |
| Q62689 | Jak2 | Tyrosine-protein kinase JAK2 | Rattus norvegicus (Rat) | SS |
| Q63272 | Jak3 | Tyrosine-protein kinase JAK3 | Rattus norvegicus (Rat) | SS |
| P32577 | Csk | Tyrosine-protein kinase CSK | Rattus norvegicus (Rat) | SS |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | Caenorhabditis elegans | SS |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| G5EE56 | src-1 | Tyrosine protein-kinase src-1 | Caenorhabditis elegans | SS |
| Q2MHE4 | HT1 | Serine/threonine/tyrosine-protein kinase HT1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O22558 | STY8 | Serine/threonine-protein kinase STY8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8RWL6 | STY17 | Serine/threonine-protein kinase STY17 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| F4JTP5 | STY46 | Serine/threonine-protein kinase STY46 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| A1A5H8 | yes1 | Tyrosine-protein kinase yes | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| F1RDG9 | fynb | Tyrosine-protein kinase fynb | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O12990 | jak1 | Tyrosine-protein kinase JAK1 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| Q1JPZ3 | src | Proto-oncogene tyrosine-protein kinase Src | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6EWH2 | fyna | Tyrosine-protein kinase fyna | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MVSWDKAHLG | PKYVGLWDFK | ARTDEELSFQ | AGDLLHVTKK | EELWWWATLL | DAEGKALAEG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| YVPHNYLAEK | ETVESEPWFF | GCISRSEAMH | RLQAEDNSKG | AFLIRVSQKP | GADYVLSVRD |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AQAVRHYRIW | KNNEGRLHLN | EAVSFSNLSE | LVDYHKTQSL | SHGLQLSMPC | WKHKTEPLPH |
| 190 | 200 | 210 | 220 | 230 | 240 |
| WDDWERPREE | FTLCKKLGAG | YFGEVFEALW | KGQVHVAVKV | ISRDNLLHQH | TFQAEIQAMK |
| 250 | 260 | 270 | 280 | 290 | 300 |
| KLRHKHILSL | YAVATAGDPV | YIITELMPKG | NLLQLLRDSD | EKALPILELV | DFASQVAEGM |
| 310 | 320 | 330 | 340 | 350 | 360 |
| CYLESQNYIH | RDLAARNVLV | TENNLCKVGD | FGLARLVKED | IYLSHEHNVP | YKWTAPEALS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| RGHYSIKSDV | WSFGVLLHEI | FSRGQMPYPG | MSNHETFLRV | DAGYRMPCPL | ECPPNIHKLM |
| 430 | 440 | 450 | |||
| LSCWSRDPKQ | RPCFKDLCEK | LTGITRYENL | V |