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Q9WTY9

- MK13_RAT

UniProt

Q9WTY9 - MK13_RAT

Protein

Mitogen-activated protein kinase 13

Gene

Mapk13

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      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.1 Publication

    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: RGD
    2. MAP kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. intracellular signal transduction Source: UniProtKB
    3. MAPK cascade Source: GOC
    4. protein phosphorylation Source: RGD
    5. regulation of transcription, DNA-templated Source: UniProtKB-KW
    6. response to stress Source: UniProtKB-KW
    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

    BRENDAi2.7.11.24. 5301.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3045. Mapk13.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 366366Mitogen-activated protein kinase 13PRO_0000186289Add
    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

    PaxDbiQ9WTY9.
    PRIDEiQ9WTY9.

    PTM databases

    PhosphoSiteiQ9WTY9.

    Expressioni

    Gene expression databases

    GenevestigatoriQ9WTY9.

    Interactioni

    Subunit structurei

    Interacts with MAPK8IP2.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WTY9.
    SMRiQ9WTY9. Positions 1-351.
    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.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiQ9WTY9.
    PhylomeDBiQ9WTY9.

    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.

    Q9WTY9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLIRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK    50
    VAIKKLSRPF QSEIFAKRAY RELLLLKHMH HENVIGLLDV YTPATSVRNF 100
    QDFYLVMPFM QTDLQKIMGM EFSEEKVQYL VYQMLKGLKY IHSAGIVHRD 150
    LKPGNLAVNE DCELKILDFG LARHTDAEMT GYVVTRWYRA PEVILSWMHY 200
    NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG VPGAEFVQKL 250
    KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AVDLLDKMLE LDVDKRLTAA 300
    QALAHPLFEP LRDPEEETEA QQPFDDALER ENLSVDEWKQ HIYKEIANFS 350
    PIARKDSRRR SGMKLQ 366
    Length:366
    Mass (Da):42,051
    Last modified:November 1, 1999 - v1
    Checksum:i09F6E65092F2E8D8
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF092534 mRNA. Translation: AAD23376.1.
    UniGeneiRn.207195.

    Genome annotation databases

    UCSCiRGD:3045. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF092534 mRNA. Translation: AAD23376.1 .
    UniGenei Rn.207195.

    3D structure databases

    ProteinModelPortali Q9WTY9.
    SMRi Q9WTY9. Positions 1-351.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q9WTY9.

    Proteomic databases

    PaxDbi Q9WTY9.
    PRIDEi Q9WTY9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:3045. rat.

    Organism-specific databases

    RGDi 3045. Mapk13.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q9WTY9.
    PhylomeDBi Q9WTY9.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 5301.

    Gene expression databases

    Genevestigatori Q9WTY9.

    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. "Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines."
      Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R., Tan T.-H.
      J. Biol. Chem. 274:7095-7102(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: PHOSPHORYLATION, FUNCTION.
    3. "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.
    4. "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_RAT
    AccessioniPrimary (citable) accession number: Q9WTY9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 109 of the entry and version 1 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3