P41241
Gene name |
Csk |
Protein name |
Tyrosine-protein kinase CSK |
Names |
C-Src kinase, Protein-tyrosine kinase MPK-2, p50CSK |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:12988 |
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
TYROSINE-PROTEIN KINASE (PTHR24418) |
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.
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 |
9-70 (SH3 domain) |
Relief mechanism |
Partner binding |
Assay |
Mutagenesis experiment, Structural analysis |
Accessory elements
331-351 (Activation loop from InterPro)
Target domain |
9-70 (SH3 domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
2 structures for P41241
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1JEG | NMR | - | A | 1-83 | PDB |
| AF-P41241-F1 | Predicted | AlphaFoldDB |
27 variants for P41241
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389056415 | 38 | I>F | No | EVA | |
| rs3389042570 | 40 | A>V | No | EVA | |
| rs3400436122 | 42 | T>I | No | EVA | |
| rs3400309301 | 43 | K>* | No | EVA | |
| rs3389046126 | 55 | G>S | No | EVA | |
| rs3389050989 | 112 | Y>S | No | EVA | |
| rs3400180614 | 126 | V>A | No | EVA | |
| rs3388996265 | 130 | R>H | No | EVA | |
| rs3389052178 | 151 | Q>R | No | EVA | |
| rs3389023256 | 155 | H>Q | No | EVA | |
| rs3389023288 | 171 | K>* | No | EVA | |
| rs3389036069 | 174 | E>G | No | EVA | |
| rs3389041132 | 175 | G>A | No | EVA | |
| rs3389042573 | 176 | T>A | No | EVA | |
| rs3389052160 | 187 | G>D | No | EVA | |
| rs3389041081 | 196 | K>M | No | EVA | |
| rs3399630689 | 224 | I>V | No | EVA | |
| rs3389014998 | 232 | A>T | No | EVA | |
| rs3389048308 | 263 | Y>* | No | EVA | |
| rs3389036050 | 272 | G>V | No | EVA | |
| rs3389015048 | 275 | V>G | No | EVA | |
| rs3388996222 | 275 | V>M | No | EVA | |
| rs33644792 | 312 | H>P | No | EVA | |
| rs3389048273 | 316 | A>T | No | EVA | |
| rs3388996201 | 328 | A>T | No | EVA | |
| rs3399630717 | 335 | L>H | No | EVA | |
| rs3389041145 | 352 | W>* | No | EVA |
No associated diseases with P41241
No regional properties for P41241
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for P41241 | |||
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.2 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24418 | TYROSINE-PROTEIN KINASE |
| PANTHER Subfamily | PTHR24418:SF407 | TYROSINE-PROTEIN KINASE CSK |
| PANTHER Protein Class | non-receptor tyrosine protein kinase | |
| PANTHER Pathway Category |
Integrin signalling pathway Csk Parkinson disease Src kinase CCKR signaling map CSK T cell activation Csk |
|
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
10 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. |
| metal ion binding | Binding to a metal ion. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction |
| proline-rich region binding | Binding to a proline-rich region, i.e. a region that contains a high proportion of proline residues, in a protein. |
| protein kinase A catalytic subunit binding | Binding to one or both of the catalytic subunits of protein kinase A. |
| protein phosphatase binding | Binding to a protein phosphatase. |
| protein tyrosine kinase activity | Catalysis of the reaction |
| protein tyrosine kinase binding | Binding to protein tyrosine kinase. |
| transferase activity | Catalysis of the transfer of a group, e.g. a methyl group, glycosyl group, acyl group, phosphorus-containing, or other groups, from one compound (generally regarded as the donor) to another compound (generally regarded as the acceptor). Transferase is the systematic name for any enzyme of EC class 2. |
18 GO annotations of biological process
| Name | Definition |
|---|---|
| adaptive immune response | An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory). |
| adherens junction organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments. |
| cellular response to peptide hormone 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 peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. |
| 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. |
| negative regulation of bone resorption | Any process that stops, prevents, or reduces the frequency, rate or extent of bone resorption. |
| negative regulation of cell population proliferation | Any process that stops, prevents or reduces the rate or extent of cell proliferation. |
| negative regulation of ERK1 and ERK2 cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| negative regulation of Golgi to plasma membrane protein transport | Any process that stops, prevents, or reduces the frequency, rate or extent of the transport of proteins from the Golgi to the plasma membrane. |
| negative regulation of interleukin-6 production | Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-6 production. |
| negative regulation of kinase activity | Any process that stops, prevents, or reduces the frequency, rate or extent of kinase activity, the catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule. |
| negative regulation of low-density lipoprotein particle clearance | Any process that decreases the rate, frequency or extent of low-density lipoprotein particle clearance. Low-density lipoprotein particle clearance is the process in which a low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded. |
| negative regulation of phagocytosis | Any process that stops, prevents, or reduces the frequency, rate or extent of phagocytosis. |
| oligodendrocyte differentiation | The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system. |
| positive regulation of MAP kinase activity | Any process that activates or increases the frequency, rate or extent of MAP kinase activity. |
| 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). |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of Fc receptor mediated stimulatory signaling pathway | Any process that modulates the rate, frequency or extent of the Fc receptor mediated stimulatory signaling pathway.. |
| regulation of T cell activation | Any process that modulates the frequency, rate or extent of T cell activation. |
92 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A0JNB0 | FYN | Tyrosine-protein kinase Fyn | Bos taurus (Bovine) | SS |
| Q3ZC95 | BTK | Tyrosine-protein kinase | Bos taurus (Bovine) | EV SS |
| Q0VBZ0 | CSK | Tyrosine-protein kinase CSK | Bos taurus (Bovine) | SS |
| P42683 | LCK | Proto-oncogene tyrosine-protein kinase LCK | 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 |
| P41239 | CSK | Tyrosine-protein kinase CSK | 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 |
| 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 |
| 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 |
| P41240 | CSK | Tyrosine-protein kinase CSK | 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 |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | 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 |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| P32577 | Csk | Tyrosine-protein kinase CSK | 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 |
| 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 |
| MSAIQAAWPS | GTECIAKYNF | HGTAEQDLPF | CKGDVLTIVA | VTKDPNWYKA | KNKVGREGII |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PANYVQKREG | VKAGTKLSLM | PWFHGKITRE | QAERLLYPPE | TGLFLVREST | NYPGDYTLCV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SCEGKVEHYR | IMYHASKLSI | DEEVYFENLM | QLVEHYTTDA | DGLCTRLIKP | KVMEGTVAAQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DEFYRSGWAL | NMKELKLLQT | IGKGEFGDVM | LGDYRGNKVA | VKCIKNDATA | QAFLAEASVM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TQLRHSNLVQ | LLGVIVEEKG | GLYIVTEYMA | KGSLVDYLRS | RGRSVLGGDC | LLKFSLDVCE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| AMEYLEGNNF | VHRDLAARNV | LVSEDNVAKV | SDFGLTKEAS | STQDTGKLPV | KWTAPEALRE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KKFSTKSDVW | SFGILLWEIY | SFGRVPYPRI | PLKDVVPRVE | KGYKMDAPDG | CPPAVYEVMK |
| 430 | 440 | ||||
| NCWHLDAATR | PTFLQLREQL | EHIKTHELHL |