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P49186

- MK09_RAT

UniProt

P49186 - MK09_RAT

Protein

Mitogen-activated protein kinase 9

Gene

Mapk9

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei55 – 551ATPPROSITE-ProRule annotation
    Active sitei151 – 1511Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi32 – 409ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: RGD
    2. cysteine-type endopeptidase activator activity involved in apoptotic process Source: RGD
    3. JUN kinase activity Source: RGD
    4. mitogen-activated protein kinase kinase kinase binding Source: RGD
    5. protein binding Source: UniProtKB
    6. transcription factor binding Source: RGD

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GOC
    2. cellular response to growth factor stimulus Source: RGD
    3. cellular response to interleukin-1 Source: RGD
    4. cellular response to lipopolysaccharide Source: RGD
    5. cellular response to tumor necrosis factor Source: RGD
    6. cellular response to UV Source: RGD
    7. central nervous system development Source: RGD
    8. JNK cascade Source: RGD
    9. JUN phosphorylation Source: RGD
    10. neuron projection development Source: RGD
    11. positive regulation of apoptotic process Source: RGD
    12. positive regulation of apoptotic signaling pathway Source: Ensembl
    13. positive regulation of cell morphogenesis involved in differentiation Source: RGD
    14. positive regulation of chemokine production Source: RGD
    15. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
    16. positive regulation of macrophage derived foam cell differentiation Source: Ensembl
    17. positive regulation of nitric oxide biosynthetic process Source: RGD
    18. positive regulation of nitric-oxide synthase biosynthetic process Source: RGD
    19. positive regulation of prostaglandin biosynthetic process Source: RGD
    20. positive regulation of prostaglandin secretion Source: RGD
    21. positive regulation of protein phosphorylation Source: RGD
    22. positive regulation of transcription, DNA-templated Source: RGD
    23. protein phosphorylation Source: RGD
    24. protein targeting to mitochondrion Source: RGD
    25. regulation of JNK cascade Source: RGD
    26. regulation of protein ubiquitination Source: RGD
    27. release of cytochrome c from mitochondria Source: RGD
    28. response to amine Source: RGD
    29. response to cadmium ion Source: Ensembl
    30. response to drug Source: RGD
    31. response to mechanical stimulus Source: RGD
    32. response to organic substance Source: RGD
    33. response to toxic substance Source: RGD

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 5301.
    ReactomeiREACT_195202. FCERI mediated MAPK activation.
    REACT_203770. Oxidative Stress Induced Senescence.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 9 (EC:2.7.11.24)
    Short name:
    MAP kinase 9
    Short name:
    MAPK 9
    Alternative name(s):
    SAPK-alpha
    Stress-activated protein kinase JNK2
    c-Jun N-terminal kinase 2
    p54-alpha
    Gene namesi
    Name:Mapk9
    Synonyms:Jnk2, Prkm9
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi628847. Mapk9.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. cytosol Source: MGI
    3. mitochondrion Source: RGD
    4. nucleus Source: RGD

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 423423Mitogen-activated protein kinase 9PRO_0000186275Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei183 – 1831Phosphothreonine; by MAP2K7By similarity
    Modified residuei185 – 1851Phosphotyrosine; by MAP2K4By similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP49186.
    PRIDEiP49186.

    PTM databases

    PhosphoSiteiP49186.

    Expressioni

    Gene expression databases

    ArrayExpressiP49186.
    GenevestigatoriP49186.

    Interactioni

    Subunit structurei

    Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with NFATC4 and DCLK2. Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 and GSK3B By similarity. Interacts with MECOM.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi248408. 1 interaction.
    IntActiP49186. 2 interactions.
    MINTiMINT-5027617.
    STRINGi10116.ENSRNOP00000003987.

    Structurei

    3D structure databases

    ProteinModelPortaliP49186.
    SMRiP49186. Positions 7-363.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini26 – 321296Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi183 – 1853TXY

    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.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP49186.
    KOiK04440.
    OMAiSSMSTEH.
    OrthoDBiEOG7PCJGV.
    PhylomeDBiP49186.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008351. MAPK_JNK.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    PRINTSiPR01772. JNKMAPKINASE.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Alpha-2 (identifier: P49186-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSDSKSDGQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI    50
    NVAVKKLSRP FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE 100
    FQDVYLVMEL MDANLCQVIH MELDHERMSY LLYQMLCGIK HLHSAGIIHR 150
    DLKPSNIVVK SDCTLKILDF GLARTACTNF MMTPYVVTRY YRAPEVILGM 200
    GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ LGTPSAEFMK 250
    KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK 300
    MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE 350
    EWKELIYKEV MDWEERSKNG VKDQPSDAAV SSKATPSQSS SINDISSMST 400
    EHTLASDTDS SLDASTGPLE GCR 423
    Length:423
    Mass (Da):48,017
    Last modified:February 1, 1996 - v1
    Checksum:iEE549B9F4F12F421
    GO
    Isoform Alpha-1 (identifier: P49186-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         216-230: GELVKGCVIFQGTDH → AEMVLHKSCSPGRDY

    Show »
    Length:423
    Mass (Da):48,107
    Checksum:i6419E1052BDC0292
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei216 – 23015GELVK…QGTDH → AEMVLHKSCSPGRDY in isoform Alpha-1. 1 PublicationVSP_004838Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27112 mRNA. Translation: AAA42109.1.
    L27111 mRNA. Translation: AAA42108.1.
    PIRiS43968.
    RefSeqiNP_001257473.1. NM_001270544.1.
    NP_059018.1. NM_017322.2. [P49186-1]
    XP_006246379.1. XM_006246317.1. [P49186-1]
    UniGeneiRn.177202.
    Rn.9910.

    Genome annotation databases

    EnsembliENSRNOT00000003987; ENSRNOP00000003987; ENSRNOG00000002823. [P49186-1]
    GeneIDi50658.
    KEGGirno:50658.
    UCSCiRGD:628847. rat. [P49186-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27112 mRNA. Translation: AAA42109.1 .
    L27111 mRNA. Translation: AAA42108.1 .
    PIRi S43968.
    RefSeqi NP_001257473.1. NM_001270544.1.
    NP_059018.1. NM_017322.2. [P49186-1 ]
    XP_006246379.1. XM_006246317.1. [P49186-1 ]
    UniGenei Rn.177202.
    Rn.9910.

    3D structure databases

    ProteinModelPortali P49186.
    SMRi P49186. Positions 7-363.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248408. 1 interaction.
    IntActi P49186. 2 interactions.
    MINTi MINT-5027617.
    STRINGi 10116.ENSRNOP00000003987.

    PTM databases

    PhosphoSitei P49186.

    Proteomic databases

    PaxDbi P49186.
    PRIDEi P49186.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000003987 ; ENSRNOP00000003987 ; ENSRNOG00000002823 . [P49186-1 ]
    GeneIDi 50658.
    KEGGi rno:50658.
    UCSCi RGD:628847. rat. [P49186-1 ]

    Organism-specific databases

    CTDi 5601.
    RGDi 628847. Mapk9.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00550000074271.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P49186.
    KOi K04440.
    OMAi SSMSTEH.
    OrthoDBi EOG7PCJGV.
    PhylomeDBi P49186.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 5301.
    Reactomei REACT_195202. FCERI mediated MAPK activation.
    REACT_203770. Oxidative Stress Induced Senescence.

    Miscellaneous databases

    NextBioi 610470.
    PROi P49186.

    Gene expression databases

    ArrayExpressi P49186.
    Genevestigatori P49186.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008351. MAPK_JNK.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PRINTSi PR01772. JNKMAPKINASE.
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS01351. MAPK. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2), PARTIAL PROTEIN SEQUENCE.
      Tissue: Brain.
    2. "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death."
      Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H.
      EMBO J. 19:2958-2968(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MECOM.

    Entry informationi

    Entry nameiMK09_RAT
    AccessioniPrimary (citable) accession number: P49186
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 135 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, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3