UniProtKB - Q3UMW7 (MAPK3_MOUSE)
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Protein
MAP kinase-activated protein kinase 3
Gene
Mapkapk3
Organism
Mus musculus (Mouse)
Status
Functioni
Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X2-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression.2 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.
Enzyme regulationi
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 75 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 168 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 52 – 60 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium-dependent protein serine/threonine kinase activity Source: GO_Central
- calmodulin binding Source: GO_Central
- calmodulin-dependent protein kinase activity Source: GO_Central
- mitogen-activated protein kinase binding Source: GO_Central
- protein serine/threonine kinase activity Source: UniProtKB
- signal transducer activity Source: GO_Central
GO - Biological processi
- cell surface receptor signaling pathway Source: GO_Central
- macropinocytosis Source: UniProtKB
- MAPK cascade Source: GO_Central
- peptidyl-serine phosphorylation Source: MGI
- protein autophosphorylation Source: GO_Central
- response to cytokine Source: UniProtKB
- response to lipopolysaccharide Source: UniProtKB
- toll-like receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-171007. p38MAPK events. R-MMU-2559580. Oxidative Stress Induced Senescence. R-MMU-4420097. VEGFA-VEGFR2 Pathway. R-MMU-450302. activated TAK1 mediates p38 MAPK activation. |
Names & Taxonomyi
Protein namesi | Recommended name: MAP kinase-activated protein kinase 3 (EC:2.7.11.1)Short name: MAPK-activated protein kinase 3 Short name: MAPKAP kinase 3 Short name: MAPKAP-K3 Short name: MAPKAPK-3 Short name: MK-3 |
Gene namesi | Name:Mapkapk3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2143163. Mapkapk3. |
Pathology & Biotechi
Disruption phenotypei
No visible phenotype. Mice are fertile and do not exhibit behavioral phenotype. Mice do not show decreased production of inflammatory cytokines such as TNF and IL6 upon LPS-stimulation. Mice lacking both Mapkapk2 and Mapkapk3 show further reduction of TNF production, compared to mice lacking only Mapkapk2. These data suggest that Mapkapk3 may function additively in stress-induced cytokine production. MAPKAPK3 knockdown homozygous mice develop Bruch's membrane abnormal thickening and thinning progressing with age (PubMed:26744326).2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 203 | T → A: Prevents degradation of isoform 3. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086294 | 1 – 384 | MAP kinase-activated protein kinase 3Add BLAST | 384 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 203 | Phosphothreonine; by MAPK142 Publications | 1 | |
Modified residuei | 253 | Phosphoserine; by MAPK14By similarity | 1 | |
Modified residuei | 309 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 315 | Phosphothreonine; by MAPK14By similarity | 1 |
Post-translational modificationi
Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1 (By similarity). Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313. Isoform 3 is degraded following phosphorylation at Thr-203.By similarity2 Publications
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q3UMW7. |
MaxQBi | Q3UMW7. |
PaxDbi | Q3UMW7. |
PeptideAtlasi | Q3UMW7. |
PRIDEi | Q3UMW7. |
PTM databases
iPTMneti | Q3UMW7. |
PhosphoSitePlusi | Q3UMW7. |
Expressioni
Tissue specificityi
Ubiquitously expressed (at protein level). Isoform 3 is expressed in skeletal muscles and heart.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000032577. |
ExpressionAtlasi | Q3UMW7. baseline and differential. |
Genevisiblei | Q3UMW7. MM. |
Interactioni
Subunit structurei
Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4 (By similarity).By similarity
GO - Molecular functioni
- calmodulin binding Source: GO_Central
- mitogen-activated protein kinase binding Source: GO_Central
Protein-protein interaction databases
BioGridi | 221912. 2 interactors. |
STRINGi | 10090.ENSMUSP00000035194. |
Structurei
3D structure databases
ProteinModelPortali | Q3UMW7. |
SMRi | Q3UMW7. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 46 – 306 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 261 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 309 – 345 | Autoinhibitory helixBy similarityAdd BLAST | 37 | |
Regioni | 347 – 371 | p38 MAPK-binding siteBy similarityAdd BLAST | 25 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 337 – 346 | Nuclear export signal (NES)By similarity | 10 | |
Motifi | 352 – 355 | Bipartite nuclear localization signal 1By similarity | 4 | |
Motifi | 366 – 370 | Bipartite nuclear localization signal 2By similarity | 5 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0604. Eukaryota. ENOG410XP8F. LUCA. |
GeneTreei | ENSGT00900000140876. |
HOGENOMi | HOG000233031. |
HOVERGENi | HBG106948. |
InParanoidi | Q3UMW7. |
KOi | K04444. |
OMAi | RMGQYGF. |
OrthoDBi | EOG091G14PL. |
PhylomeDBi | Q3UMW7. |
TreeFami | TF312891. |
Family and domain databases
Gene3Di | 4.10.1170.10. 1 hit. |
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR027442. MAPKAPK_C. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_kinase_AS. |
Pfami | View protein in Pfam PF00069. Pkinase. 1 hit. |
SMARTi | View protein in SMART SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF56112. SSF56112. 1 hit. |
PROSITEi | View protein in PROSITE PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q3UMW7-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MDGETAGEKG SLVPPPGALG GSALGGAPAP GVRREPKKYA VTDDYQLSKQ
60 70 80 90 100
VLGLGVNGKV LECYHRRSGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV
110 120 130 140 150
RILDVYENMH HGKRCLLIVM ECMEGGELFS RIQERGDQAF TEREAAEIMR
160 170 180 190 200
DIGTAIQFLH SRNIAHRDVK PENLLYTSKE KDAVLKLTDF GFAKETTQNA
210 220 230 240 250
LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG FPPFYSNTGQ
260 270 280 290 300
AISPGMKRRI RLGQYSFPNP EWLDVSEDAK QLIRLLLKTD PTERLTIMQF
310 320 330 340 350
MNHPWINQSM VVPQTPLYTA RVLQEDKDHW DDVKEEMTSA LATMRVDYDQ
360 370 380
VKIKDLKTSN NRLLNKRRKK QAGSSSASQG CNNQ
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 216 | L → P in BAE25981 (PubMed:16141072).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016386 | 212 – 249 | APEVL…YSNTG → GESFACGLHPHCCRML in isoform 2. 1 PublicationAdd BLAST | 38 | |
Alternative sequenceiVSP_042175 | 238 – 266 | LCGFP…LGQYS → NPWWSHRPHSTQPECSRKTK ITGMTSRKR in isoform 3. CuratedAdd BLAST | 29 | |
Alternative sequenceiVSP_016387 | 250 – 384 | Missing in isoform 2. 1 PublicationAdd BLAST | 135 | |
Alternative sequenceiVSP_042176 | 267 – 384 | Missing in isoform 3. CuratedAdd BLAST | 118 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK087496 mRNA. Translation: BAC39897.1. AK144637 mRNA. Translation: BAE25981.1. AK151881 mRNA. Translation: BAE30767.1. AK172344 mRNA. Translation: BAE42958.1. AK172578 mRNA. Translation: BAE43076.1. AL672070 Genomic DNA. Translation: CAQ12134.1. CH466560 Genomic DNA. Translation: EDL21175.1. BC031467 mRNA. Translation: AAH31467.1. |
CCDSi | CCDS23487.1. [Q3UMW7-1] CCDS85722.1. [Q3UMW7-3] |
RefSeqi | NP_001303620.1. NM_001316691.1. [Q3UMW7-3] NP_849238.1. NM_178907.3. [Q3UMW7-1] XP_006511679.1. XM_006511616.3. [Q3UMW7-1] |
UniGenei | Mm.222612. Mm.445242. |
Genome annotation databases
Ensembli | ENSMUST00000035194; ENSMUSP00000035194; ENSMUSG00000032577. [Q3UMW7-1] ENSMUST00000192054; ENSMUSP00000141342; ENSMUSG00000032577. [Q3UMW7-3] |
GeneIDi | 102626. |
KEGGi | mmu:102626. |
UCSCi | uc009rkx.1. mouse. [Q3UMW7-1] uc009rla.1. mouse. [Q3UMW7-2] uc012hab.1. mouse. [Q3UMW7-3] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | MAPK3_MOUSE | |
Accessioni | Q3UMW7Primary (citable) accession number: Q3UMW7 Secondary accession number(s): B0QZU7 Q8K0G3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | December 6, 2005 | |
Last modified: | March 28, 2018 | |
This is version 119 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |