O54992
Gene name |
Mapkapk5 |
Protein name |
MAP kinase-activated protein kinase 5 |
Names |
MAPK-activated protein kinase 5, MAPKAP kinase 5, MAPKAPK-5 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:17165 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
SERINE/THREONINE-PROTEIN KINASE (PTHR24349) |
Descriptions
MAPKAPK5 is a MAP kinase-activated protein kinase 5, activated by stress-related extracellular stimuli, and is able to shuttle between the nucleus (unstimulated cells) and the cytoplasm (stimulated cells). The proposed autoinhibitory region is within the C-terminal domain of MAPKAPK5, contains 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 MAPKAPK5 prevents exportin binding to NES. Phosphorylation of MAPKAPK5 at threonine 182 by p38 MAPK induces a conformational change, thus unmasks and increases the activity of NES.
Autoinhibitory domains (AIDs)
Target domain |
22-304 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
Mutagenesis experiment |
Accessory elements
168-188 (Activation loop from InterPro)
Target domain |
22-304 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
1 structures for O54992
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O54992-F1 | Predicted | AlphaFoldDB |
4 variants for O54992
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs50729478 | 33 | S>G | No | Ensembl | |
| rs1131791310 | 99 | L>* | No | Ensembl | |
| rs1135392506 | 100 | I>S | No | Ensembl | |
| rs864303085 | 473 | Q>R | No | Ensembl |
No associated diseases with O54992
1 regional properties for O54992
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| active_site | Serine/threonine-protein kinase, active site | 144 - 156 | IPR008271 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24349 | SERINE/THREONINE-PROTEIN KINASE |
| PANTHER Subfamily | PTHR24349:SF179 | MAP KINASE-ACTIVATED PROTEIN KINASE 5 |
| PANTHER Protein Class |
non-receptor serine/threonine protein kinase
protein modifying enzyme |
|
| PANTHER Pathway Category | No pathway information available | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| 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. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
| septin cytoskeleton | The part of the cytoskeleton (the internal framework of a cell) composed of septins and associated proteins. Includes septin cytoskeleton-associated complexes. |
10 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. |
| p53 binding | Binding to one of the p53 family of proteins. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. |
| 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. |
11 GO annotations of biological process
| Name | Definition |
|---|---|
| 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 TOR signaling | Any process that stops, prevents, or reduces the frequency, rate or extent of TOR signaling. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| positive regulation of dendritic spine development | Any process that increases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. |
| positive regulation of telomerase activity | Any process that activates or increases the frequency, rate or extent of telomerase activity, the catalysis of the reaction: deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). |
| positive regulation of telomere capping | Any process that activates or increases the frequency, rate or extent of telomere capping. |
| positive regulation of telomere maintenance via telomerase | Any process that activates or increases the frequency, rate or extent of the addition of telomeric repeats by telomerase. |
| 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). |
| Ras protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state. |
| regulation of translation | Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA. |
| stress-induced premature senescence | A cellular senescence process associated with the dismantling of a cell as a response to environmental factors such as hydrogen peroxide or X-rays. |
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 |
| P49137 | MAPKAPK2 | MAP kinase-activated protein kinase 2 | Homo sapiens (Human) | EV |
| Q16644 | MAPKAPK3 | MAP kinase-activated protein kinase 3 | Homo sapiens (Human) | SS |
| Q8IW41 | MAPKAPK5 | MAP kinase-activated protein kinase 5 | Homo sapiens (Human) | SS |
| Q3UMW7 | Mapkapk3 | MAP kinase-activated protein kinase 3 | Mus musculus (Mouse) | SS |
| P49138 | Mapkapk2 | MAP kinase-activated protein kinase 2 | Mus musculus (Mouse) | EV |
| 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 |
| MSEDSDMEKA | IKETSILEEY | SINWTQKLGA | GISGPVRVCV | KKSTQERFAL | KILLDRPKAR |
| 70 | 80 | 90 | 100 | 110 | 120 |
| NEVRLHMMCA | THPNIVQIIE | VFANSVQFPH | ESSPRARLLI | VMEMMEGGEL | FHRISQHRHF |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TEKQASQVTK | QIALALQHCH | LLNIAHRDLK | PENLLFKDNS | LDAPVKLCDF | GFAKVDQGDL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| MTPQFTPYYV | APQVLEAQRR | HQKEKSGIIP | TSPTPYTYNK | SCDLWSLGVI | IYVMLCGYPP |
| 250 | 260 | 270 | 280 | 290 | 300 |
| FYSKHHSRTI | PKDMRKKIMT | GSFEFPEEEW | SQISEMAKDV | VRKLLKVKPE | ERLTIEGVLD |
| 310 | 320 | 330 | 340 | 350 | 360 |
| HPWLNSTEAL | DNVLPSAQLM | MDKAVVAGIQ | QAHAEQLANM | RIQDLKVSLK | PLHSVNNPIL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| RKRKLLGTKP | KDGIYIHDHE | NGTEDSNVAL | EKLRDVIAQC | ILPQAGKGEN | EDEKLNEVMQ |
| 430 | 440 | 450 | 460 | 470 | |
| EAWKYNRECK | LLRDALQSFS | WNGRGFTDKV | DRLKLAEVVK | QVIEEQTLPH | EPQ |