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Q9WUI1

- MK11_MOUSE

UniProt

Q9WUI1 - MK11_MOUSE

Protein

Mitogen-activated protein kinase 11

Gene

Mapk11

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    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 – 531ATPPROSITE-ProRule annotation
    Binding sitei71 – 711NilotinibBy similarity
    Active sitei168 – 1681Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi30 – 389ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    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

    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

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

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

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei180 – 1801Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K61 Publication
    Modified residuei182 – 1821Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K61 Publication
    Modified residuei323 – 3231Phosphotyrosine; by ZAP70By 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 308285Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    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

    Experimental Info

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

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 123 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