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Q9Z1B7

- MK13_MOUSE

UniProt

Q9Z1B7 - MK13_MOUSE

Protein

Mitogen-activated protein kinase 13

Gene

Mapk13

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 2 (12 Feb 2003)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 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 such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.

    Enzyme regulationi

    Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei54 – 541ATPPROSITE-ProRule annotation
    Active sitei150 – 1501Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. intracellular signal transduction Source: UniProtKB
    3. peptidyl-serine phosphorylation Source: Ensembl
    4. positive regulation of interleukin-6 production Source: Ensembl
    5. regulation of transcription, DNA-templated Source: UniProtKB-KW
    6. response to osmotic stress Source: Ensembl
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell cycle, Stress response, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_207601. p38MAPK events.
    REACT_211125. NOD1/2 Signaling Pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 13 (EC:2.7.11.24)
    Short name:
    MAP kinase 13
    Short name:
    MAPK 13
    Alternative name(s):
    Mitogen-activated protein kinase p38 delta
    Short name:
    MAP kinase p38 delta
    Stress-activated protein kinase 4
    Gene namesi
    Name:Mapk13
    Synonyms:Serk4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:1346864. Mapk13.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 366366Mitogen-activated protein kinase 13PRO_0000186287Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei180 – 1801Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7By similarity
    Modified residuei182 – 1821Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7By similarity
    Modified residuei350 – 3501PhosphoserineBy similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1 By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9Z1B7.
    PaxDbiQ9Z1B7.
    PRIDEiQ9Z1B7.

    PTM databases

    PhosphoSiteiQ9Z1B7.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9Z1B7.
    BgeeiQ9Z1B7.
    CleanExiMM_MAPK13.
    GenevestigatoriQ9Z1B7.

    Interactioni

    Subunit structurei

    Interacts with MAPK8IP2.1 Publication

    Protein-protein interaction databases

    BioGridi204968. 82 interactions.
    STRINGi10090.ENSMUSP00000004986.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z1B7.
    SMRiQ9Z1B7. Positions 2-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 308284Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    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.
    GeneTreeiENSGT00680000099969.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiQ9Z1B7.
    KOiK04441.
    OMAiEHPYFDN.
    OrthoDBiEOG7PCJGV.
    PhylomeDBiQ9Z1B7.
    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.

    Q9Z1B7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLTRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK    50
    VAIKKLSRPF QSEIFAKRAY RELLLLKHMH HENVIGLLDV FTPASSLRSF 100
    HDFYLVMPFM QTDLQKIMGM EFSEDKVQYL VYQMLKGLKY IHSAGIVHRD 150
    LKPGNLAVNE DCELKILDFG LARHTDTEMT GYVVTRWYRA PEVILSWMHY 200
    NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG VPGAEFVQKL 250
    KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AADLLDKMLE LDVDKRLTAA 300
    QALAHPFFEP FRDPEEETEA QQPFDDALEH EKLSVDEWKQ HIYKEISNFS 350
    PIARKDSRRR SGMKLQ 366
    Length:366
    Mass (Da):42,072
    Last modified:February 12, 2003 - v2
    Checksum:i45D23D7BD404B3FE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti45 – 451K → R in AAD09229. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U81823 mRNA. Translation: AAD09229.1.
    BC001992 mRNA. Translation: AAH01992.1.
    CCDSiCCDS28584.1.
    RefSeqiNP_036080.2. NM_011950.2.
    UniGeneiMm.27970.

    Genome annotation databases

    EnsembliENSMUST00000004986; ENSMUSP00000004986; ENSMUSG00000004864.
    GeneIDi26415.
    KEGGimmu:26415.
    UCSCiuc008bro.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U81823 mRNA. Translation: AAD09229.1 .
    BC001992 mRNA. Translation: AAH01992.1 .
    CCDSi CCDS28584.1.
    RefSeqi NP_036080.2. NM_011950.2.
    UniGenei Mm.27970.

    3D structure databases

    ProteinModelPortali Q9Z1B7.
    SMRi Q9Z1B7. Positions 2-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204968. 82 interactions.
    STRINGi 10090.ENSMUSP00000004986.

    Chemistry

    BindingDBi Q9Z1B7.
    ChEMBLi CHEMBL2111473.

    PTM databases

    PhosphoSitei Q9Z1B7.

    Proteomic databases

    MaxQBi Q9Z1B7.
    PaxDbi Q9Z1B7.
    PRIDEi Q9Z1B7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000004986 ; ENSMUSP00000004986 ; ENSMUSG00000004864 .
    GeneIDi 26415.
    KEGGi mmu:26415.
    UCSCi uc008bro.2. mouse.

    Organism-specific databases

    CTDi 5603.
    MGIi MGI:1346864. Mapk13.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00680000099969.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q9Z1B7.
    KOi K04441.
    OMAi EHPYFDN.
    OrthoDBi EOG7PCJGV.
    PhylomeDBi Q9Z1B7.
    TreeFami TF105100.

    Enzyme and pathway databases

    Reactomei REACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_207601. p38MAPK events.
    REACT_211125. NOD1/2 Signaling Pathway.

    Miscellaneous databases

    NextBioi 304421.
    PROi Q9Z1B7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Z1B7.
    Bgeei Q9Z1B7.
    CleanExi MM_MAPK13.
    Genevestigatori Q9Z1B7.

    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. Jiang Y., Han J.
      Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "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: Mammary gland.
    3. "Fibroblast growth factor homologous factors are intracellular signaling proteins."
      Schoorlemmer J., Goldfarb M.
      Curr. Biol. 11:793-797(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAPK8IP2.
    4. Cited for: FUNCTION IN PHOSPHORYLATION OF PRKD1.
    5. "Evidence of p38gamma and p38delta involvement in cell transformation processes."
      Cerezo-Guisado M.I., del Reino P., Remy G., Kuma Y., Arthur J.S., Gallego-Ortega D., Cuenda A.
      Carcinogenesis 32:1093-1099(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "p38delta mitogen-activated protein kinase regulates skin homeostasis and tumorigenesis."
      Efimova T.
      Cell Cycle 9:498-505(2010) [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 nameiMK13_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z1B7
    Secondary accession number(s): Q99M57
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: February 12, 2003
    Last modified: October 1, 2014
    This is version 128 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