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Q9WUI1 (MK11_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 11

Short name=MAP kinase 11
Short name=MAPK 11
EC=2.7.11.24
Alternative name(s):
Mitogen-activated protein kinase p38 beta
Short name=MAP kinase p38 beta
Short name=p38B
Gene names
Name:Mapk11
Synonyms:Prkm11
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length364 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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. Ref.5

Subunit structure

Interacts with HDAC3 and DUSP16 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Domain

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

Post-translational modification

Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6, which activates the enzyme. Ref.5

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Mapk14P4781110EBI-645081,EBI-298727

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 364364Mitogen-activated protein kinase 11
PRO_0000186281

Regions

Domain24 – 308285Protein kinase
Nucleotide binding30 – 389ATP By similarity
Region106 – 1105Inhibitor-binding By similarity
Region168 – 1692Inhibitor-binding By similarity
Motif180 – 1823TXY

Sites

Active site1681Proton acceptor By similarity
Binding site531ATP By similarity
Binding site711Nilotinib By similarity

Amino acid modifications

Modified residue1801Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K6 Probable
Modified residue1821Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K6 Probable
Modified residue3231Phosphotyrosine; by ZAP70 By similarity

Experimental info

Sequence conflict1731R → P in AAD30116. Ref.1
Sequence conflict3121H → R in AAD30116. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9WUI1 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 75C16E9972508220

FASTA36441,397
        10         20         30         40         50         60 
MSGPRAGFYR QELNKTVWEV PQRLQGLRPV GSGAYGSVCS AYDARLRQKV AVKKLSRPFQ 

        70         80         90        100        110        120 
SLIHARRTYR ELRLLKHLKH ENVIGLLDVF TPATSIEDFS EVYLVTTLMG ADLNNIVKCQ 

       130        140        150        160        170        180 
ALSDEHVQFL VYQLLRGLKY IHSAGIIHRD LKPSNVAVNE DCELRILDFG LARQADEEMT 

       190        200        210        220        230        240 
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLQGK ALFPGNDYID QLKRIMEVVG 

       250        260        270        280        290        300 
TPSPEVLAKI SSEHARTYIQ SLPPMPQKDL SSVFHGANPL AIDLLGRMLV LDSDQRVSAA 

       310        320        330        340        350        360 
EALAHAYFSQ YHDPDDEPEA EPYDESVEAK ERTLEEWKEL TYQEVLSFKP LEPSQLPGTH 


EIEQ 

« Hide

References

« Hide 'large scale' references
[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]"Differential activation of p38MAPK isoforms by MKK6 and MKK3."
Remy G., Risco A.M., Inesta-Vaquera F.A., Gonzalez-Teran B., Sabio G., Davis R.J., Cuenda A.
Cell. Signal. 22:660-667(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF135185 mRNA. Translation: AAD30116.1.
CH466550 Genomic DNA. Translation: EDL04368.1.
BC092526 mRNA. Translation: AAH92526.1.
CCDSCCDS27741.1.
RefSeqNP_035291.4. NM_011161.5.
UniGeneMm.91969.

3D structure databases

ProteinModelPortalQ9WUI1.
SMRQ9WUI1. Positions 3-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9WUI1. 1 interaction.
MINTMINT-1204530.

Chemistry

BindingDBQ9WUI1.
ChEMBLCHEMBL2111473.

PTM databases

PhosphoSiteQ9WUI1.

Proteomic databases

PaxDbQ9WUI1.
PRIDEQ9WUI1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000088823; ENSMUSP00000086204; ENSMUSG00000053137.
GeneID19094.
KEGGmmu:19094.
UCSCuc007xfp.2. mouse.

Organism-specific databases

CTD5600.
MGIMGI:1338024. Mapk11.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074271.
HOVERGENHBG014652.
InParanoidQ569F1.
KOK04441.
OMAETIGGCE.
OrthoDBEOG7PCJGV.
TreeFamTF105100.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_217867. Metabolism of RNA.
REACT_224594. Organelle biogenesis and maintenance.

Gene expression databases

BgeeQ9WUI1.
CleanExMM_MAPK11.
GenevestigatorQ9WUI1.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01773. P38MAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio295658.
PROQ9WUI1.
SOURCESearch...

Entry information

Entry nameMK11_MOUSE
AccessionPrimary (citable) accession number: Q9WUI1
Secondary accession number(s): Q569F1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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