Q04736
Gene name |
Yes1 (Yes) |
Protein name |
Tyrosine-protein kinase Yes |
Names |
EC 2.7.10.2 , Proto-oncogene c-Yes , p61-Yes |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22612 |
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
Autoinhibitory domains (AIDs)
Target domain |
275-528 (Protein kinase domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Target domain |
275-528 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Target domain |
275-528 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
275-528 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
411-435 (Activation loop from InterPro)
Target domain |
275-524 (Tyrosine-protein kinase, catalytic domain) |
Relief mechanism |
|
Assay |
|
References
- Register AC et al. (2014) "SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family", Biochemistry, 53, 6910-23
- Boggon TJ et al. (2004) "Structure and regulation of Src family kinases", Oncogene, 23, 7918-27
- Engen JR et al. (2008) "Structure and dynamic regulation of Src-family kinases", Cellular and molecular life sciences : CMLS, 65, 3058-73
- Alvarado JJ et al. (2010) "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism", The Journal of biological chemistry, 285, 35455-61
- Schindler T et al. (1999) "Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor", Molecular cell, 3, 639-48
- Williams JC et al. (1997) "The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions", Journal of molecular biology, 274, 757-75
- Meng Y et al. (2014) "Locking the active conformation of c-Src kinase through the phosphorylation of the activation loop", Journal of molecular biology, 426, 423-35
- Laham LE et al. (2000) "The activation loop in Lck regulates oncogenic potential by inhibiting basal kinase activity and restricting substrate specificity", Oncogene, 19, 3961-70
- Furlan G et al. (2014) "Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters", The Journal of biological chemistry, 289, 28514-25
- Kükenshöner T et al. (2017) "Selective Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies", Journal of molecular biology, 429, 1364-1380
- Wang Q et al. (2010) "Multicolor monitoring of dysregulated protein kinases in chronic myelogenous leukemia", ACS chemical biology, 5, 887-95
- Sotirellis N et al. (1995) "Autophosphorylation induces autoactivation and a decrease in the Src homology 2 domain accessibility of the Lyn protein kinase", The Journal of biological chemistry, 270, 29773-80
- Williams NK et al. (2009) "Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state", The Journal of biological chemistry, 284, 284-291
Autoinhibited structure
Activated structure
3 structures for Q04736
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2YT6 | NMR | - | A | 71-167 | PDB |
| 5MTJ | X-ray | 195 A | A | 147-260 | PDB |
| AF-Q04736-F1 | Predicted | AlphaFoldDB |
20 variants for Q04736
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388749839 | 11 | S>G | No | EVA | |
| rs3388738659 | 15 | K>N | No | EVA | |
| rs3388750798 | 15 | K>T | No | EVA | |
| rs3388737987 | 34 | V>M | No | EVA | |
| rs3388759511 | 39 | V>L | No | EVA | |
| rs3388745601 | 49 | S>L | No | EVA | |
| rs3388759507 | 78 | V>M | No | EVA | |
| rs3395506513 | 120 | N>K | No | EVA | |
| rs1134879951 | 166 | A>V | No | EVA | |
| rs3388755663 | 223 | T>K | No | EVA | |
| rs3388750805 | 311 | M>K | No | EVA | |
| rs3388753189 | 338 | S>P | No | EVA | |
| rs3388737944 | 341 | P>S | No | EVA | |
| rs3388738000 | 431 | K>N | No | EVA | |
| rs3388753264 | 440 | E>K | No | EVA | |
| rs3388759522 | 448 | T>S | No | EVA | |
| rs3388753637 | 460 | Q>H | No | EVA | |
| rs1133260369 | 462 | E>K | No | EVA | |
| rs1133623089 | 464 | V>I | No | EVA | |
| rs1132594154 | 465 | T>I | No | EVA |
No associated diseases with Q04736
8 regional properties for Q04736
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 275 - 528 | IPR000719 |
| domain | SH2 domain | 154 - 253 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 276 - 524 | IPR001245 |
| domain | SH3 domain | 89 - 150 | IPR001452 |
| active_site | Tyrosine-protein kinase, active site | 390 - 402 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 281 - 303 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 275 - 524 | IPR020635 |
| domain | Tyrosine-protein kinase Yes, SH3 domain | 92 - 149 | IPR035751 |
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 | |
8 GO annotations of cellular component
| Name | Definition |
|---|---|
| actin filament | A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane. |
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| extrinsic component of cytoplasmic side of plasma membrane | The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| Golgi apparatus | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| postsynaptic specialization, intracellular component | A network of proteins adjacent to the postsynaptic membrane. Its major components include the proteins that spatially and functionally organize neurotransmitter receptors in the adjacent membrane, such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| enzyme binding | Binding to an enzyme, a protein with catalytic activity. |
| epidermal growth factor receptor binding | Binding to an epidermal growth factor receptor. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction |
| phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
| 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. |
| transmembrane transporter binding | Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other. |
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. |
| cellular response to platelet-derived growth factor stimulus | 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 platelet-derived growth factor stimulus. |
| 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. |
| cellular response to transforming growth factor beta stimulus | 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 transforming growth factor beta stimulus. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| 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 peptidyl-tyrosine phosphorylation | Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| regulation of glucose transmembrane transport | Any process that modulates the frequency, rate or extent of glucose transport across a membrane. Glucose transport is the directed movement of the hexose monosaccharide glucose into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| 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. |
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 |
| Q05876 | FYN | Tyrosine-protein kinase Fyn | Gallus gallus (Chicken) | SS |
| Q75R65 | JAK2 | Tyrosine-protein kinase JAK2 | Gallus gallus (Chicken) | SS |
| P09324 | YES1 | Tyrosine-protein kinase Yes | Gallus gallus (Chicken) | SS |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | 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 |
| Q13882 | PTK6 | Protein-tyrosine kinase 6 | Homo sapiens (Human) | EV |
| P08631 | HCK | Tyrosine-protein kinase HCK | Homo sapiens (Human) | EV |
| P42685 | FRK | Tyrosine-protein kinase FRK | Homo sapiens (Human) | EV |
| Q06187 | BTK | Tyrosine-protein kinase BTK | Homo sapiens (Human) | EV |
| P07947 | YES1 | Tyrosine-protein kinase Yes | 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 |
| 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 |
| Q64434 | Ptk6 | Protein-tyrosine kinase 6 | 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 |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | 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 |
| 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 |
| A1A5H8 | yes1 | Tyrosine-protein kinase yes | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGCIKSKENK | SPAIKYTPEN | LTEPVSPSAS | HYGVEHATVA | PTSSTKGASV | NFNSLSMTPF |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GGSSGVTPFG | GASSSFSVVS | SSYPTGLTGG | VTIFVALYDY | EARTTEDLSF | KKGERFQIIN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| NTEGDWWEAR | SIATGKSGYI | PSNYVVPADS | IQAEEWYFGK | MGRKDAERLL | LNPGNQRGIF |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LVRESETTKG | AYSLSIRDWD | EVRGDNVKHY | KIRKLDNGGY | YITTRAQFDT | LQKLVKHYTE |
| 250 | 260 | 270 | 280 | 290 | 300 |
| HADGLCHKLT | TVCPTVKPQT | QGLAKDAWEI | PRESLRLEVK | LGQGCFGEVW | MGTWNGTTKV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| AIKTLKPGTM | MPEAFLQEAQ | IMKKLRHDKL | VPLYAVVSEE | PIYIVTEFMS | KGSLLDFLKE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GDGKYLKLPQ | LVDMAAQIAD | GMAYIERMNY | IHRDLRAANI | LVGENLICKI | ADFGLARLIE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| DNEYTARQGA | KFPIKWTAPE | AALYGRFTIK | SDVWSFGILQ | TELVTKGRVP | YPGMVNREVL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| EQVERGYRMP | CPQGCPESLH | ELMNLCWKKD | PDERPTFEYI | QSFLEDYFTA | TEPQYQPGEN |
| L |