P49138
Gene name |
Mapkapk2 (Rps6kc1) |
Protein name |
MAP kinase-activated protein kinase 2 |
Names |
MAPK-activated protein kinase 2, MAPKAP kinase 2, MAPKAP-K2, MAPKAPK-2, MK-2, MK2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:17164 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
SERINE/THREONINE-PROTEIN KINASE (PTHR24349) |
Descriptions
MAPKAPK2 is a stress-activated serine/threonine-protein kinase. MAPKAPK2, contains an autoinhibitory α-helix overlapping with a leucine-rich nuclear export signal (NES), and also lies close to the nuclear localization signal (NLS). The closed conformation of MAPKAPK2 prevents exportin binding to NES. Phosphorylation of MAPKAPK2 at threonine 317 induces a conformational change, thus unmasks and increases the activity of NES.
Autoinhibitory domains (AIDs)
Target domain |
5-311 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
Mutagenesis experiment, Peptide inhibitor test |
Accessory elements
192-214 (Activation loop from InterPro)
Target domain |
50-311 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Seternes OM et al. (2002) "Both binding and activation of p38 mitogen-activated protein kinase (MAPK) play essential roles in regulation of the nucleocytoplasmic distribution of MAPK-activated protein kinase 5 by cellular stress", Molecular and cellular biology, 22, 6931-45
- Engel K et al. (1998) "Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation", The EMBO journal, 17, 3363-71
Autoinhibited structure
Activated structure
1 structures for P49138
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P49138-F1 | Predicted | AlphaFoldDB |
No variants for P49138
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P49138 | |||||
No associated diseases with P49138
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24349 | SERINE/THREONINE-PROTEIN KINASE |
| PANTHER Subfamily | PTHR24349:SF63 | MAP KINASE-ACTIVATED PROTEIN KINASE 2 |
| PANTHER Protein Class |
non-receptor serine/threonine protein kinase
protein modifying enzyme |
|
| PANTHER Pathway Category |
Ras Pathway MAPKAP Interleukin signaling pathway MAPKAPK2 PDGF signaling pathway MAPKAPK2 p38 MAPK pathway MAPKAP-K2 VEGF signaling pathway MAPKAPK2/3 Angiogenesis MAPKAPK2/3 |
|
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| 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. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| calcium-dependent protein serine/threonine kinase activity | Calcium-dependent catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; and ATP + a protein threonine = ADP + protein threonine phosphate. |
| calmodulin binding | Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states. |
| calmodulin-dependent protein kinase activity | Calmodulin-dependent catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; and ATP + a protein threonine = ADP + protein threonine phosphate. |
| mitogen-activated protein kinase binding | Binding to a mitogen-activated protein kinase. |
| protein serine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. |
| protein serine/threonine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. |
| protein serine/threonine/tyrosine kinase activity | Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
19 GO annotations of biological process
| Name | Definition |
|---|---|
| 3'-UTR-mediated mRNA stabilization | An mRNA stabilization process in which one or more RNA-binding proteins associate with the 3'-untranslated region (UTR) of an mRNA. |
| cellular response to DNA damage 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 stimulus indicating damage to its DNA from environmental insults or errors during metabolism. |
| cellular response to vascular endothelial 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 vascular endothelial growth factor stimulus. |
| inflammatory response | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. |
| inner ear development | The process whose specific outcome is the progression of the inner ear over time, from its formation to the mature structure. |
| 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. |
| macropinocytosis | An endocytosis process that results in the uptake of liquid material by cells from their external environment by the 'ruffling' of the cell membrane to form heterogeneously sized intracellular vesicles called macropinosomes, which can be up to 5 micrometers in size. |
| mRNA stabilization | Prevention of degradation of mRNA molecules. In the absence of compensating changes in other processes, the slowing of mRNA degradation can result in an overall increase in the population of active mRNA molecules. |
| p38MAPK cascade | An intracellular protein kinase cascade containing at least a p38 MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| positive regulation of tumor necrosis factor production | Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production. |
| 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 interleukin-6 production | Any process that modulates the frequency, rate, or extent of interleukin-6 production. |
| regulation of tumor necrosis factor production | Any process that modulates the frequency, rate or extent of tumor necrosis factor production. |
| response to cytokine | 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 a cytokine stimulus. |
| response to lipopolysaccharide | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
| toll-like receptor signaling pathway | The series of molecular signals initiated by a ligand binding to a toll-like receptor on the surface of a target cell. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. |
| vascular endothelial growth factor receptor signaling pathway | The series of molecular signals initiated by a ligand binding to a vascular endothelial growth factor receptor (VEGFR) on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q3SYZ2 | MAPKAPK3 | MAP kinase-activated protein kinase 3 | Bos taurus (Bovine) | SS |
| P49071 | MAPk-Ak2 | MAP kinase-activated protein kinase 2 | Drosophila melanogaster (Fruit fly) | SS |
| Q16644 | MAPKAPK3 | MAP kinase-activated protein kinase 3 | Homo sapiens (Human) | SS |
| Q8IW41 | MAPKAPK5 | MAP kinase-activated protein kinase 5 | Homo sapiens (Human) | SS |
| P49137 | MAPKAPK2 | MAP kinase-activated protein kinase 2 | Homo sapiens (Human) | EV |
| O54992 | Mapkapk5 | MAP kinase-activated protein kinase 5 | Mus musculus (Mouse) | EV |
| Q3UMW7 | Mapkapk3 | MAP kinase-activated protein kinase 3 | Mus musculus (Mouse) | SS |
| O08605 | Mknk1 | MAP kinase-interacting serine/threonine-protein kinase 1 | Mus musculus (Mouse) | PR |
| Q8CDB0 | Mknk2 | MAP kinase-interacting serine/threonine-protein kinase 2 | Mus musculus (Mouse) | PR |
| P08414 | Camk4 | Calcium/calmodulin-dependent protein kinase type IV | Mus musculus (Mouse) | SS |
| Q66H84 | Mapkapk3 | MAP kinase-activated protein kinase 3 | Rattus norvegicus (Rat) | SS |
| Q965G5 | mak-2 | MAP kinase-activated protein kinase mak-2 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MLSGSPGQTP | PAPFPSPPPP | APAQPPPPFP | QFHVKSGLQI | RKNAITDDYK | VTSQVLGLGI |
| 70 | 80 | 90 | 100 | 110 | 120 |
| NGKVLRIFDK | RTQQKFALKM | LQDCPKARRE | VELHWRASQC | PHIVHIVDVY | ENLYAGRKCL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LIVMECLDGG | ELFSRIQDRG | DQAFTEREAS | EIMKSIGEAI | QYLHSINIAH | RDVKPENLLY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| TSKRPNAILK | LTDFGFAKET | TSHNSLTTPC | YTPYYVAPEV | LGPEKYDKSC | DMWSLGVIMY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ILLCGYPPFY | SNHGLAISPG | MKTRIRMGQY | EFPNPEWSEV | SEEVKMLIRN | LLKTEPTQRM |
| 310 | 320 | 330 | 340 | 350 | 360 |
| TITEFMNHPW | IMQSTKVPQT | PLHTSRVLKE | DKERWEDVKE | EMTSALATMR | VDYEQIKIKK |
| 370 | 380 | ||||
| IEDASNPLLL | KRRKKARAVE | DAALAH |