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Q9WUI1

- MK11_MOUSE

UniProt

Q9WUI1 - MK11_MOUSE

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Protein
Mitogen-activated protein kinase 11
Gene
Mapk11, Prkm11
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium By similarity.

Enzyme regulationi

Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531ATP By similarity
Binding sitei71 – 711Nilotinib By similarity
Active sitei168 – 1681Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi30 – 389ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB
  3. protein binding Source: IntAct
Complete GO annotation...

GO - Biological processi

  1. intracellular signal transduction Source: UniProtKB
  2. regulation of transcription, DNA-templated Source: UniProtKB-KW
  3. response to stress Source: UniProtKB-KW
  4. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_188970. Oxidative Stress Induced Senescence.
REACT_198696. KSRP destabilizes mRNA.
REACT_204811. Activation of the AP-1 family of transcription factors.
REACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_207601. p38MAPK events.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_215063. ERK/MAPK targets.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 15

Organism-specific databases

MGIiMGI:1338024. Mapk11.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 364364Mitogen-activated protein kinase 11
PRO_0000186281Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K6 Inferred
Modified residuei182 – 1821Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K6 Inferred
Modified residuei323 – 3231Phosphotyrosine; by ZAP70 By similarity

Post-translational modificationi

Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6, which activates the enzyme.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9WUI1.
PRIDEiQ9WUI1.

PTM databases

PhosphoSiteiQ9WUI1.

Expressioni

Gene expression databases

BgeeiQ9WUI1.
CleanExiMM_MAPK11.
GenevestigatoriQ9WUI1.

Interactioni

Subunit structurei

Interacts with HDAC3 and DUSP16 By similarity.

Binary interactionsi

WithEntry#Exp.IntActNotes
Mapk14P4781110EBI-645081,EBI-298727

Protein-protein interaction databases

IntActiQ9WUI1. 1 interaction.
MINTiMINT-1204530.

Structurei

3D structure databases

ProteinModelPortaliQ9WUI1.
SMRiQ9WUI1. Positions 3-349.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 308285Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni106 – 1105Inhibitor-binding By similarity
Regioni168 – 1692Inhibitor-binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi180 – 1823TXY

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074271.
HOVERGENiHBG014652.
InParanoidiQ569F1.
KOiK04441.
OMAiETIGGCE.
OrthoDBiEOG7PCJGV.
TreeFamiTF105100.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9WUI1-1 [UniParc]FASTAAdd to Basket

« Hide

MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV    50
AVKKLSRPFQ SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS 100
EVYLVTTLMG ADLNNIVKCQ ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD 150
LKPSNVAVNE DCELRILDFG LARQADEEMT GYVATRWYRA PEIMLNWMHY 200
NQTVDIWSVG CIMAELLQGK ALFPGNDYID QLKRIMEVVG TPSPEVLAKI 250
SSEHARTYIQ SLPPMPQKDL SSVFHGANPL AIDLLGRMLV LDSDQRVSAA 300
EALAHAYFSQ YHDPDDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP 350
LEPSQLPGTH EIEQ 364
Length:364
Mass (Da):41,397
Last modified:July 27, 2011 - v2
Checksum:i75C16E9972508220
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti173 – 1731R → P in AAD30116. 1 Publication
Sequence conflicti312 – 3121H → R in AAD30116. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF135185 mRNA. Translation: AAD30116.1.
CH466550 Genomic DNA. Translation: EDL04368.1.
BC092526 mRNA. Translation: AAH92526.1.
CCDSiCCDS27741.1.
RefSeqiNP_035291.4. NM_011161.5.
UniGeneiMm.91969.

Genome annotation databases

EnsembliENSMUST00000088823; ENSMUSP00000086204; ENSMUSG00000053137.
GeneIDi19094.
KEGGimmu:19094.
UCSCiuc007xfp.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Mm.91969.

3D structure databases

ProteinModelPortali Q9WUI1.
SMRi Q9WUI1. Positions 3-349.
ModBasei Search...

Protein-protein interaction databases

IntActi Q9WUI1. 1 interaction.
MINTi MINT-1204530.

Chemistry

BindingDBi Q9WUI1.
ChEMBLi CHEMBL2111473.

PTM databases

PhosphoSitei Q9WUI1.

Proteomic databases

PaxDbi Q9WUI1.
PRIDEi Q9WUI1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074271.
HOVERGENi HBG014652.
InParanoidi Q569F1.
KOi K04441.
OMAi ETIGGCE.
OrthoDBi EOG7PCJGV.
TreeFami TF105100.

Enzyme and pathway databases

Reactomei REACT_188970. Oxidative Stress Induced Senescence.
REACT_198696. KSRP destabilizes mRNA.
REACT_204811. Activation of the AP-1 family of transcription factors.
REACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_207601. p38MAPK events.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_215063. ERK/MAPK targets.

Miscellaneous databases

NextBioi 295658.
PROi Q9WUI1.
SOURCEi Search...

Gene expression databases

Bgeei Q9WUI1.
CleanExi MM_MAPK11.
Genevestigatori Q9WUI1.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01773. P38MAPKINASE.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The primary structure of murine p38beta."
    Han J.
    Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  4. "MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts."
    Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S.
    Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACTIVATION OF RPS6KA5/MSK1 AND RPS6KA4/MSK2.
  5. Cited for: PHOSPHORYLATION, ENZYME REGULATION.
  6. "In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance."
    Shi Y., Gaestel M.
    Biol. Chem. 383:1519-1536(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  7. "Mechanisms and functions of p38 MAPK signalling."
    Cuadrado A., Nebreda A.R.
    Biochem. J. 429:403-417(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.

Entry informationi

Entry nameiMK11_MOUSE
AccessioniPrimary (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: September 3, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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