P52332
Gene name |
Jak1 |
Protein name |
Tyrosine-protein kinase JAK1 |
Names |
EC 2.7.10.2 , Janus kinase 1 , JAK-1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
|
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
Autoinhibitory domains (AIDs)
Target domain |
874-1153 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
874-1153 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
874-1153 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
1019-1045 (Activation loop from InterPro)
Target domain |
874-1152 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
1019-1045 (Activation loop from InterPro)
Target domain |
874-1152 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Ma W et al. (2009) "Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias", The Journal of molecular diagnostics : JMD, 11, 49-53
- Saharinen P et al. (2003) "Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain", Molecular biology of the cell, 14, 1448-59
- Kershaw NJ et al. (2013) "SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition", Nature structural & molecular biology, 20, 469-76
- Hubbard SR (2017) "Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase", Frontiers in endocrinology, 8, 361
- Wang J et al. (2023) "Triple-action inhibitory mechanism of allosteric TYK2-specific inhibitors", bioRxiv : the preprint server for biology, ,
- Lupardus PJ et al. (2014) "Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition", Proceedings of the National Academy of Sciences of the United States of America, 111, 8025-30
Autoinhibited structure
Activated structure
3 structures for P52332
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 7T6F | EM | 360 A | A/B | 1-1153 | PDB |
| 8EWY | EM | 550 A | A/B | 1-1153 | PDB |
| AF-P52332-F1 | Predicted | AlphaFoldDB |
No variants for P52332
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P52332 | |||||
No associated diseases with P52332
14 regional properties for P52332
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 825 - 1097 | IPR000719 |
| domain | EGF-like domain | 216 - 252 | IPR000742-1 |
| domain | EGF-like domain | 267 - 299 | IPR000742-2 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 825 - 1092 | IPR001245 |
| domain | Laminin-type EGF domain | 230 - 275 | IPR002049-1 |
| domain | Laminin-type EGF domain | 314 - 342 | IPR002049-2 |
| domain | Fibronectin type III | 444 - 541 | IPR003961-1 |
| domain | Fibronectin type III | 543 - 637 | IPR003961-2 |
| domain | Fibronectin type III | 640 - 735 | IPR003961-3 |
| domain | Immunoglobulin-like domain | 350 - 440 | IPR007110 |
| active_site | Tyrosine-protein kinase, active site | 961 - 973 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 831 - 856 | IPR017441 |
| domain | Tyrosine-protein kinase, receptor Tie-2, Ig-like domain 1, N-terminal | 24 - 118 | IPR018941 |
| domain | Tyrosine-protein kinase, catalytic domain | 825 - 1093 | IPR020635 |
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 | |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoskeleton | A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| endomembrane system | A collection of membranous structures involved in transport within the cell. The main components of the endomembrane system are endoplasmic reticulum, Golgi bodies, vesicles, cell membrane and nuclear envelope. Members of the endomembrane system pass materials through each other or though the use of vesicles. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| CCR5 chemokine receptor binding | Binding to a CCR5 chemokine receptor. |
| growth hormone receptor binding | Binding to a growth hormone receptor. |
| metal ion binding | Binding to a metal ion. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction |
| protein tyrosine kinase activity | Catalysis of the reaction |
12 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. |
| cellular response to interleukin-3 | 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 an interleukin-3 stimulus. |
| cellular response to interleukin-7 | 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 an interleukin-7 stimulus. |
| cytokine-mediated signaling pathway | The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| enzyme-linked receptor protein 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 catalytic activity or is closely associated with an enzyme such as a protein kinase, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| growth hormone receptor signaling pathway via JAK-STAT | The process in which STAT proteins (Signal Transducers and Activators of Transcription) are activated by members of the JAK (janus activated kinase) family of tyrosine kinases, following the binding of physiological ligands to the growth hormone receptor. Once activated, STATs dimerize and translocate to the nucleus and modulate the expression of target genes. |
| interleukin-2-mediated signaling pathway | The series of molecular signals initiated by interleukin-2 binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| 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. |
| positive regulation of receptor signaling pathway via STAT | Any process that activates or increases the frequency, rate or extent of receptor signaling pathway via STAT. |
| receptor signaling pathway via JAK-STAT | Any process in which STAT proteins (Signal Transducers and Activators of Transcription) and JAK (Janus Activated Kinase) proteins convey a signal to trigger a change in the activity or state of a cell. The receptor signaling pathway via JAK-STAT begins with activation of a receptor and proceeeds through STAT protein activation by members of the JAK family of tyrosine kinases. STAT proteins dimerize and subsequently translocate to the nucleus. The pathway ends with regulation of target gene expression by STAT proteins. |
| response to antibiotic | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an antibiotic stimulus. An antibiotic is a chemical substance produced by a microorganism which has the capacity to inhibit the growth of or to kill other microorganisms. |
76 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 |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| 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 |
| 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 |
| 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 |
| P23458 | JAK1 | Tyrosine-protein kinase JAK1 | Homo sapiens (Human) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | Mus musculus (Mouse) | SS |
| P16277 | Blk | Tyrosine-protein kinase Blk | Mus musculus (Mouse) | SS |
| Q62270 | Srms | Tyrosine-protein kinase Srms | Mus musculus (Mouse) | SS |
| Q64434 | Ptk6 | Protein-tyrosine kinase 6 | Mus musculus (Mouse) | SS |
| P05480 | Src | Proto-oncogene tyrosine-protein kinase Src | Mus musculus (Mouse) | EV |
| P14234 | Fgr | Tyrosine-protein kinase Fgr | Mus musculus (Mouse) | SS |
| P35991 | Btk | Tyrosine-protein kinase BTK | Mus musculus (Mouse) | EV |
| P41241 | Csk | Tyrosine-protein kinase CSK | Mus musculus (Mouse) | EV |
| P25911 | Lyn | Tyrosine-protein kinase Lyn | Mus musculus (Mouse) | EV |
| P06240 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Mus musculus (Mouse) | SS |
| P24604 | Tec | Tyrosine-protein kinase Tec | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | Mus musculus (Mouse) | SS |
| P39688 | Fyn | Tyrosine-protein kinase Fyn | Mus musculus (Mouse) | SS |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| P41242 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Mus musculus (Mouse) | SS |
| Q922K9 | Frk | Tyrosine-protein kinase FRK | Mus musculus (Mouse) | SS |
| Q62120 | Jak2 | Tyrosine-protein kinase JAK2 | Mus musculus (Mouse) | EV |
| Q62137 | Jak3 | Tyrosine-protein kinase JAK3 | Mus musculus (Mouse) | SS |
| Q9R117 | Tyk2 | Non-receptor tyrosine-protein kinase TYK2 | 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 |
| A1A5H8 | yes1 | Tyrosine-protein kinase yes | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| F1RDG9 | fynb | Tyrosine-protein kinase fynb | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 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 |
| O12990 | jak1 | Tyrosine-protein kinase JAK1 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MQYLNIKEDC | NAMAFCAKMR | SFKKTEVKQV | VPEPGVEVTF | YLLDREPLRL | GSGEYTAEEL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| CIRAAQECSI | SPLCHNLFAL | YDESTKLWYA | PNRIITVDDK | TSLRLHYRMR | FYFTNWHGTN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| DNEQSVWRHS | PKKQKNGYEK | KRVPEATPLL | DASSLEYLFA | QGQYDLIKCL | APIRDPKTEQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DGHDIENECL | GMAVLAISHY | AMMKKMQLPE | LPKDISYKRY | IPETLNKSIR | QRNLLTRMRI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NNVFKDFLKE | FNNKTICDSS | VHDLKVKYLA | TLETSTLTKH | YGAEIFETSM | LLISSENELS |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RCHSNDSGNV | LYEVMVTGNL | GIQWRQKPNV | VPVEKEKNKL | KRKKLEYNKH | KKDDERNKLR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| EEWNNFSYFP | EITHIVIKES | VVSINKQDNK | NMELKLSSRE | EALSFVSLVD | GYFRLTADAH |
| 430 | 440 | 450 | 460 | 470 | 480 |
| HYLCTDVAPP | LIVHNIQNGC | HGPICTEYAI | NKLRQEGSEE | GMYVLRWSCT | DFDNILMTVT |
| 490 | 500 | 510 | 520 | 530 | 540 |
| CFEKSEVLGG | QKQFKNFQIE | VQKGRYSLHG | SMDHFPSLRD | LMNHLKKQIL | RTDNISFVLK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| RCCQPKPREI | SNLLVATKKA | QEWQPVYSMS | QLSFDRILKK | DIIQGEHLGR | GTRTHIYSGT |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LLDYKDEEGI | AEEKKIKVIL | KVLDPSHRDI | SLAFFEAASM | MRQVSHKHIV | YLYGVCVRDV |
| 670 | 680 | 690 | 700 | 710 | 720 |
| ENIMVEEFVE | GGPLDLFMHR | KSDALTTPWK | FKVAKQLASA | LSYLEDKDLV | HGNVCTKNLL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| LAREGIDSDI | GPFIKLSDPG | IPVSVLTRQE | CIERIPWIAP | ECVEDSKNLS | VAADKWSFGT |
| 790 | 800 | 810 | 820 | 830 | 840 |
| TLWEICYNGE | IPLKDKTLIE | KERFYESRCR | PVTPSCKELA | DLMTRCMNYD | PNQRPFFRAI |
| 850 | 860 | 870 | 880 | 890 | 900 |
| MRDINKLEEQ | NPDIVSEKQP | TTEVDPTHFE | KRFLKRIRDL | GEGHFGKVEL | CRYDPEGDNT |
| 910 | 920 | 930 | 940 | 950 | 960 |
| GEQVAVKSLK | PESGGNHIAD | LKKEIEILRN | LYHENIVKYK | GICMEDGGNG | IKLIMEFLPS |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| GSLKEYLPKN | KNKINLKQQL | KYAIQICKGM | DYLGSRQYVH | RDLAARNVLV | ESEHQVKIGD |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| FGLTKAIETD | KEYYTVKDDR | DSPVFWYAPE | CLIQCKFYIA | SDVWSFGVTL | HELLTYCDSD |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| FSPMALFLKM | IGPTHGQMTV | TRLVKTLKEG | KRLPCPPNCP | DEVYQLMRKC | WEFQPSNRTT |
| 1150 | |||||
| FQNLIEGFEA | LLK |