P41242
SS
Gene name |
Matk (Ctk, Ntk) |
Protein name |
Megakaryocyte-associated tyrosine-protein kinase |
Names |
EC 2.7.10.2 , Protein kinase NTK , Tyrosine-protein kinase CTK |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:17179 |
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
The kinase Csk is the primary negative regulator of the Src‐family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes). Csk phosphorylates a tyrosine on the SFK C‐terminal tail that mediates autoinhibition. Csk is recruited to membrane-anchored SFKs and activated allosterically via its SH2 domain, which binds SFK- phosphorylated motifs in CBP/PAG1 (Csk binding protein/phosphoprotein associated with glycosphingolipid- enriched microdomains), Paxillin, Fak, the Dok family, and other tyrosine-phosphorylated proteins. Csk also binds phosphatases, including PTPN12 (PTP‐PEST) and immune‐cell PTPN22 (LYP/Pep), which dephosphorylate SFK activation loop to promote autoinhibition. <br> Purified Csk homodimerizes in competition with PTPN22 binding through an interface that is mediated by symmetrical SH3-SH3 interactions and that overlaps the phosphatase binding footprint. Mutation in SH3 impairing homodimerization enhances PTPN22 binding.
Autoinhibitory domains (AIDs)
Target domain |
46-108 (SH3 domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
233-480 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Brian BF 4th et al. (2022) "SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding", Scientific reports, 12, 5875
- Ghose R et al. (2001) "A novel, specific interaction involving the Csk SH3 domain and its natural ligand", Nature structural biology, 8, 998-1004
- 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 P41242
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P41242-F1 | Predicted | AlphaFoldDB |
No variants for P41242
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P41242 | |||||
No associated diseases with P41242
8 regional properties for P41242
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 233 - 481 | IPR000719 |
| domain | SH2 domain | 118 - 209 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 234 - 476 | IPR001245 |
| domain | SH3 domain | 46 - 108 | IPR001452 |
| active_site | Tyrosine-protein kinase, active site | 346 - 358 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 239 - 260 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 233 - 476 | IPR020635 |
| domain | CSK-like, SH2 domain | 116 - 213 | IPR035027 |
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 | |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction |
1 GO annotations of biological process
| Name | Definition |
|---|---|
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
92 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 |
| 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 |
| Q13882 | PTK6 | Protein-tyrosine kinase 6 | 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 |
| P42679 | MATK | Megakaryocyte-associated tyrosine-protein kinase | Homo sapiens (Human) | SS |
| 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 |
| P48025 | Syk | Tyrosine-protein kinase SYK | Mus musculus (Mouse) | SS |
| P43404 | Zap70 | Tyrosine-protein kinase ZAP-70 | Mus musculus (Mouse) | SS |
| Q64434 | Ptk6 | Protein-tyrosine kinase 6 | Mus musculus (Mouse) | SS |
| P14234 | Fgr | Tyrosine-protein kinase Fgr | Mus musculus (Mouse) | SS |
| P25911 | Lyn | Tyrosine-protein kinase Lyn | Mus musculus (Mouse) | EV |
| P39688 | Fyn | Tyrosine-protein kinase Fyn | 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 |
| P16277 | Blk | Tyrosine-protein kinase Blk | Mus musculus (Mouse) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | Mus musculus (Mouse) | SS |
| Q922K9 | Frk | Tyrosine-protein kinase FRK | Mus musculus (Mouse) | SS |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| P35991 | Btk | Tyrosine-protein kinase BTK | Mus musculus (Mouse) | EV |
| P24604 | Tec | Tyrosine-protein kinase Tec | Mus musculus (Mouse) | SS |
| P41241 | Csk | Tyrosine-protein kinase CSK | Mus musculus (Mouse) | EV |
| 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 |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | Caenorhabditis elegans | SS |
| G5EE56 | src-1 | Tyrosine protein-kinase src-1 | Caenorhabditis elegans | SS |
| Q8I7I5 | rol-3 | Protein roller-3 | Caenorhabditis elegans | PR |
| O16262 | nipi-4 | Protein nipi-4 | Caenorhabditis elegans | PR |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| F4JTP5 | STY46 | Serine/threonine-protein kinase STY46 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O22558 | STY8 | Serine/threonine-protein kinase STY8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q2MHE4 | HT1 | Serine/threonine/tyrosine-protein kinase HT1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8RWL6 | STY17 | Serine/threonine-protein kinase STY17 | 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 |
| MARRSSRVSW | LAFEGWESRD | LPRVSPRLFG | AWHPAPAAAR | MPTRWAPGTQ | CMTKCENSRP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KPGELAFRKG | DMVTILEACE | DKSWYRAKHH | GSGQEGLLAA | AALRHGEALS | TDPKLSLMPW |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FHGKISGQEA | IQQLQPPEDG | LFLVRESARH | PGDYVLCVSF | GRDVIHYRVL | HRDGHLTIDE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| AVCFCNLMDM | VEHYTKDKGA | ICTKLVKPRR | KQGAKSAEEE | LAKAGWLLDL | QHLTLGAQIG |
| 250 | 260 | 270 | 280 | 290 | 300 |
| EGEFGAVLQG | EYLGQKVAVK | NIKCDVTAQA | FLDETAVMTK | LQHRNLVRLL | GVILHHGLYI |
| 310 | 320 | 330 | 340 | 350 | 360 |
| VMEHVSKGNL | VNFLRTRGRA | LVSTSQLLQF | ALHVAEGMEY | LESKKLVHRD | LAARNILVSE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| DLVAKVSDFG | LAKAERKGLD | SSRLPVKWTA | PEALKNGRFS | SKSDVWSFGV | LLWEVFSYGR |
| 430 | 440 | 450 | 460 | 470 | 480 |
| APYPKMSLKE | VSEAVEKGYR | MEPPDGCPGS | VHTLMGSCWE | AEPARRPPFR | KIVEKLGREL |
| 490 | 500 | ||||
| RSVGVSAPAG | GQEAEGSAPT | RSQDP |