UniProtKB - Q9WUI1 (MK11_MOUSE)
Mitogen-activated protein kinase 11
Mapk11
Functioni
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment.
1 PublicationCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 53 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 71 | NilotinibBy similarity | 1 | |
Active sitei | 168 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 30 – 38 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: MGI
- MAP kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: Reactome
- protein serine kinase activity Source: RHEA
GO - Biological processi
- bone development Source: MGI
- cellular response to interleukin-1 Source: MGI
- cellular response to virus Source: MGI
- intracellular signal transduction Source: GO_Central
- MAPK cascade Source: MGI
- negative regulation of cardiac muscle cell proliferation Source: MGI
- osteoblast differentiation Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of interleukin-12 production Source: MGI
- protein phosphorylation Source: MGI
- regulation of cardiac muscle cell proliferation Source: MGI
- stress-activated MAPK cascade Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Stress response, Transcription, Transcription regulation |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-168638, NOD1/2 Signaling Pathway R-MMU-171007, p38MAPK events R-MMU-198753, ERK/MAPK targets R-MMU-2559580, Oxidative Stress Induced Senescence R-MMU-376172, DSCAM interactions R-MMU-4420097, VEGFA-VEGFR2 Pathway R-MMU-450302, activated TAK1 mediates p38 MAPK activation R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-525793, Myogenesis R-MMU-5668599, RHO GTPases Activate NADPH Oxidases R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase 11 (EC:2.7.11.24)Short name: MAP kinase 11 Short name: MAPK 11 Alternative name(s): Mitogen-activated protein kinase p38 beta Short name: MAP kinase p38 beta Short name: p38B |
Gene namesi | Name:Mapk11 Synonyms:Prkm11 |
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:1338024, Mapk11 |
VEuPathDBi | HostDB:ENSMUSG00000053137 |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186281 | 1 – 364 | Mitogen-activated protein kinase 11Add BLAST | 364 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 180 | Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K61 Publication | 1 | |
Modified residuei | 182 | Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K61 Publication | 1 | |
Modified residuei | 323 | Phosphotyrosine; by ZAP70By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | Q9WUI1 |
PaxDbi | Q9WUI1 |
PRIDEi | Q9WUI1 |
ProteomicsDBi | 291465 |
PTM databases
iPTMneti | Q9WUI1 |
PhosphoSitePlusi | Q9WUI1 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000053137, Expressed in cerebral cortex and 218 other tissues |
Genevisiblei | Q9WUI1, MM |
Interactioni
Subunit structurei
Interacts with HDAC3 and DUSP16.
By similarityBinary interactionsi
Q9WUI1
With | #Exp. | IntAct |
---|---|---|
Mapk14 [P47811] | 10 | EBI-645081,EBI-298727 |
Protein-protein interaction databases
BioGRIDi | 202374, 163 interactors |
IntActi | Q9WUI1, 1 interactor |
MINTi | Q9WUI1 |
STRINGi | 10090.ENSMUSP00000086204 |
Chemistry databases
BindingDBi | Q9WUI1 |
Miscellaneous databases
RNActi | Q9WUI1, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 24 – 308 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 285 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 106 – 110 | Inhibitor-bindingBy similarity | 5 | |
Regioni | 168 – 169 | Inhibitor-bindingBy similarity | 2 | |
Regioni | 312 – 331 | DisorderedSequence analysisAdd BLAST | 20 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 180 – 182 | TXY | 3 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000160790 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | Q9WUI1 |
OMAi | GRISACE |
OrthoDBi | 683132at2759 |
PhylomeDBi | Q9WUI1 |
TreeFami | TF105100 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008352, MAPK_p38-like IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01773, P38MAPKINASE |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV
60 70 80 90 100
AVKKLSRPFQ SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS
110 120 130 140 150
EVYLVTTLMG ADLNNIVKCQ ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD
160 170 180 190 200
LKPSNVAVNE DCELRILDFG LARQADEEMT GYVATRWYRA PEIMLNWMHY
210 220 230 240 250
NQTVDIWSVG CIMAELLQGK ALFPGNDYID QLKRIMEVVG TPSPEVLAKI
260 270 280 290 300
SSEHARTYIQ SLPPMPQKDL SSVFHGANPL AIDLLGRMLV LDSDQRVSAA
310 320 330 340 350
EALAHAYFSQ YHDPDDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP
360
LEPSQLPGTH EIEQ
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 173 | R → P in AAD30116 (Ref. 1) Curated | 1 | |
Sequence conflicti | 312 | H → R in AAD30116 (Ref. 1) Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF135185 mRNA Translation: AAD30116.1 CH466550 Genomic DNA Translation: EDL04368.1 BC092526 mRNA Translation: AAH92526.1 |
CCDSi | CCDS27741.1 |
RefSeqi | NP_035291.4, NM_011161.5 |
Genome annotation databases
Ensembli | ENSMUST00000088823; ENSMUSP00000086204; ENSMUSG00000053137 |
GeneIDi | 19094 |
KEGGi | mmu:19094 |
UCSCi | uc007xfp.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF135185 mRNA Translation: AAD30116.1 CH466550 Genomic DNA Translation: EDL04368.1 BC092526 mRNA Translation: AAH92526.1 |
CCDSi | CCDS27741.1 |
RefSeqi | NP_035291.4, NM_011161.5 |
3D structure databases
SMRi | Q9WUI1 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 202374, 163 interactors |
IntActi | Q9WUI1, 1 interactor |
MINTi | Q9WUI1 |
STRINGi | 10090.ENSMUSP00000086204 |
Chemistry databases
BindingDBi | Q9WUI1 |
ChEMBLi | CHEMBL4335 |
PTM databases
iPTMneti | Q9WUI1 |
PhosphoSitePlusi | Q9WUI1 |
Proteomic databases
MaxQBi | Q9WUI1 |
PaxDbi | Q9WUI1 |
PRIDEi | Q9WUI1 |
ProteomicsDBi | 291465 |
Protocols and materials databases
Antibodypediai | 28468, 507 antibodies from 38 providers |
DNASUi | 19094 |
Genome annotation databases
Ensembli | ENSMUST00000088823; ENSMUSP00000086204; ENSMUSG00000053137 |
GeneIDi | 19094 |
KEGGi | mmu:19094 |
UCSCi | uc007xfp.2, mouse |
Organism-specific databases
CTDi | 5600 |
MGIi | MGI:1338024, Mapk11 |
VEuPathDBi | HostDB:ENSMUSG00000053137 |
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000160790 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | Q9WUI1 |
OMAi | GRISACE |
OrthoDBi | 683132at2759 |
PhylomeDBi | Q9WUI1 |
TreeFami | TF105100 |
Enzyme and pathway databases
Reactomei | R-MMU-168638, NOD1/2 Signaling Pathway R-MMU-171007, p38MAPK events R-MMU-198753, ERK/MAPK targets R-MMU-2559580, Oxidative Stress Induced Senescence R-MMU-376172, DSCAM interactions R-MMU-4420097, VEGFA-VEGFR2 Pathway R-MMU-450302, activated TAK1 mediates p38 MAPK activation R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-525793, Myogenesis R-MMU-5668599, RHO GTPases Activate NADPH Oxidases R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation |
Miscellaneous databases
BioGRID-ORCSi | 19094, 1 hit in 65 CRISPR screens |
PROi | PR:Q9WUI1 |
RNActi | Q9WUI1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000053137, Expressed in cerebral cortex and 218 other tissues |
Genevisiblei | Q9WUI1, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008352, MAPK_p38-like IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01773, P38MAPKINASE |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MK11_MOUSE | |
Accessioni | Q9WUI1Primary (citable) accession number: Q9WUI1 Secondary accession number(s): Q569F1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2001 |
Last sequence update: | July 27, 2011 | |
Last modified: | February 23, 2022 | |
This is version 177 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families