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Q91Y86

- MK08_MOUSE

UniProt

Q91Y86 - MK08_MOUSE

Protein

Mitogen-activated protein kinase 8

Gene

Mapk8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone By similarity. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.By similarity5 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.1 Publication

    Enzyme regulationi

    Inhibited by SERPINB3 By similarity. 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 similarity1 Publication

    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: UniProtKB-KW
    2. histone deacetylase regulator activity Source: Ensembl
    3. JUN kinase activity Source: UniProtKB
    4. kinase activity Source: MGI
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to hydrogen peroxide Source: MGI
    2. cellular response to lipopolysaccharide Source: MGI
    3. cellular response to mechanical stimulus Source: Ensembl
    4. cellular response to nitric oxide Source: MGI
    5. determination of dorsal identity Source: MGI
    6. JNK cascade Source: UniProtKB
    7. JUN phosphorylation Source: MGI
    8. negative regulation of apoptotic process Source: Ensembl
    9. negative regulation of protein binding Source: Ensembl
    10. ossification Source: MGI
    11. peptidyl-serine phosphorylation Source: Ensembl
    12. peptidyl-threonine phosphorylation Source: MGI
    13. positive regulation of apoptotic signaling pathway Source: MGI
    14. positive regulation of deacetylase activity Source: Ensembl
    15. positive regulation of determination of dorsal identity Source: MGI
    16. positive regulation of gene expression Source: Ensembl
    17. programmed necrotic cell death Source: MGI
    18. protein phosphorylation Source: MGI
    19. regulation of gene expression Source: MGI
    20. regulation of protein localization Source: Ensembl
    21. response to cadmium ion Source: MGI
    22. response to UV Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 3474.
    ReactomeiREACT_188530. FCERI mediated MAPK activation.
    REACT_188970. Oxidative Stress Induced Senescence.
    REACT_202271. NRIF signals cell death from the nucleus.
    REACT_204811. Activation of the AP-1 family of transcription factors.
    REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_209641. NRAGE signals death through JNK.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 8 (EC:2.7.11.24)
    Short name:
    MAP kinase 8
    Short name:
    MAPK 8
    Alternative name(s):
    Stress-activated protein kinase JNK1
    c-Jun N-terminal kinase 1
    Gene namesi
    Name:Mapk8
    Synonyms:Jnk1, Prkm8
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 14

    Organism-specific databases

    MGIiMGI:1346861. Mapk8.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    At 14.5 dpc, brain intermediate zone and cortical plate are significantly thicker in mutant mice compared to wild type. The number of neuronal cells is increased in the cortical plate and intermediate zone. Cell cycle exit is decreased by 13% in the ventricular and subventricular zones. In 17.5 dpc brains, the ventricular zone was thinner in mutant mice compared to wild type animals, consistent with the increased number of neurons in the cortical plate. TUBB3 is consistently more diffuse and less structured in mutant telencephalon than in wild type.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 384384Mitogen-activated protein kinase 8PRO_0000186263Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei116 – 1161S-nitrosocysteineBy similarity
    Modified residuei183 – 1831Phosphothreonine; by MAP2K71 Publication
    Modified residuei185 – 1851Phosphotyrosine; by MAP2K41 Publication
    Modified residuei377 – 3771Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylated by TAOK2 By similarity. Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme.By similarity2 Publications

    Keywords - PTMi

    Phosphoprotein, S-nitrosylation

    Proteomic databases

    PaxDbiQ91Y86.
    PRIDEiQ91Y86.

    PTM databases

    PhosphoSiteiQ91Y86.

    Expressioni

    Developmental stagei

    At 15.5 dpc, mid to low expression throughout the midbrain, with more prominent levels in the telencephalon, especially in the intermediate zone, the midbrain roof, the olfactory epithelium, the inferior colliculus, and the medulla oblongata. telencephalon revealed concentrated (at protein level).1 Publication

    Inductioni

    In T-cells, following T-cell receptor (TCR) activation. Levels peak 48 hours after TCR and CD-28 costimulation.1 Publication

    Gene expression databases

    ArrayExpressiQ91Y86.
    BgeeiQ91Y86.
    CleanExiMM_MAPK8.
    GenevestigatoriQ91Y86.

    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. Forms a complex with MAPK8IP1 and ARHGEF28. Interacts with TP53 and WWOX. Interacts with JAMP. Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates By similarity. Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells.By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    JunP056272EBI-298784,EBI-764369

    Protein-protein interaction databases

    BioGridi204971. 16 interactions.
    IntActiQ91Y86. 7 interactions.
    MINTiMINT-1204569.
    STRINGi10090.ENSMUSP00000022504.

    Structurei

    3D structure databases

    ProteinModelPortaliQ91Y86.
    SMRiQ91Y86. Positions 7-364.
    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.
    KOiK04440.
    OrthoDBiEOG7PCJGV.
    PhylomeDBiQ91Y86.
    TreeFamiTF105100.

    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]

    Sequencei

    Sequence statusi: Complete.

    Q91Y86-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER    50
    NVAIKKLSRP FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE 100
    FQDVYIVMEL MDANLCQVIQ MELDHERMSY LLYQMLCGIK HLHSAGIIHR 150
    DLKPSNIVVK SDCTLKILDF GLARTAGTSF MMTPYVVTRY YRAPEVILGM 200
    GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ LGTPCPEFMK 250
    KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 300
    MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE 350
    EWKELIYKEV MDLEERTKNG VIRGQPSPLA QVQQ 384
    Length:384
    Mass (Da):44,229
    Last modified:December 1, 2001 - v1
    Checksum:iA7320EF933E9CF85
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005663 mRNA. Translation: BAA85875.1.
    CCDSiCCDS36869.1.
    RefSeqiNP_057909.1. NM_016700.4.
    UniGeneiMm.21495.

    Genome annotation databases

    EnsembliENSMUST00000111945; ENSMUSP00000107576; ENSMUSG00000021936.
    GeneIDi26419.
    KEGGimmu:26419.
    UCSCiuc007szt.3. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005663 mRNA. Translation: BAA85875.1 .
    CCDSi CCDS36869.1.
    RefSeqi NP_057909.1. NM_016700.4.
    UniGenei Mm.21495.

    3D structure databases

    ProteinModelPortali Q91Y86.
    SMRi Q91Y86. Positions 7-364.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204971. 16 interactions.
    IntActi Q91Y86. 7 interactions.
    MINTi MINT-1204569.
    STRINGi 10090.ENSMUSP00000022504.

    Chemistry

    BindingDBi Q91Y86.
    ChEMBLi CHEMBL1795174.

    PTM databases

    PhosphoSitei Q91Y86.

    Proteomic databases

    PaxDbi Q91Y86.
    PRIDEi Q91Y86.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000111945 ; ENSMUSP00000107576 ; ENSMUSG00000021936 .
    GeneIDi 26419.
    KEGGi mmu:26419.
    UCSCi uc007szt.3. mouse.

    Organism-specific databases

    CTDi 5599.
    MGIi MGI:1346861. Mapk8.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00550000074271.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    KOi K04440.
    OrthoDBi EOG7PCJGV.
    PhylomeDBi Q91Y86.
    TreeFami TF105100.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 3474.
    Reactomei REACT_188530. FCERI mediated MAPK activation.
    REACT_188970. Oxidative Stress Induced Senescence.
    REACT_202271. NRIF signals cell death from the nucleus.
    REACT_204811. Activation of the AP-1 family of transcription factors.
    REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_209641. NRAGE signals death through JNK.

    Miscellaneous databases

    NextBioi 304433.
    PROi Q91Y86.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q91Y86.
    Bgeei Q91Y86.
    CleanExi MM_MAPK8.
    Genevestigatori Q91Y86.

    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. "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway."
      Ito M., Yoshioka K., Akechi M., Yamashita S., Takamatsu N., Sugiyama K., Hibi M., Nakabeppu Y., Shiba T., Yamamoto K.
      Mol. Cell. Biol. 19:7539-7548(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAPK8IP3.
      Tissue: Brain.
    2. "JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases."
      Hu M.C., Qiu W.R., Wang Y.P.
      Oncogene 15:2277-2287(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF TP53.
    3. "Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity."
      Yang D., Tournier C., Wysk M., Lu H.-T., Xu J., Davis R.J., Flavell R.A.
      Proc. Natl. Acad. Sci. U.S.A. 94:3004-3009(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY MAP2K4.
      Tissue: Embryonic stem cell.
    4. "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase."
      Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J.
      Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION BY MAP2K7, COFACTOR.
    5. "JNK is required for effector T-cell function but not for T-cell activation."
      Dong C., Yang D.D., Tournier C., Whitmarsh A.J., Xu J., Davis R.J., Flavell R.A.
      Nature 405:91-94(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, INDUCTION.
      Tissue: Embryonic stem cell and T-cell.
    6. "The AP-1 repressor, JDP2, is a bona fide substrate for the c-Jun N-terminal kinase."
      Katz S., Heinrich R., Aronheim A.
      FEBS Lett. 506:196-200(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF JDP2.
    7. Cited for: SUBUNIT, PHOSPHORYLATION AT THR-183 AND TYR-185.
      Tissue: Hippocampus.
    8. "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors."
      Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.
      Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPAG9.
    9. "Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity to an EGFP-tagged protein."
      Wu J., Zhai J., Lin H., Nie Z., Ge W.-W., Garcia-Bermejo L., Muschel R.J., Schlaepfer W.W., Canete-Soler R.
      Brain Res. Mol. Brain Res. 117:27-38(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH MAPK8IP1 AND ARHGEF28.
    10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.
    11. "JAMP, a Jun N-terminal kinase 1 (JNK1)-associated membrane protein, regulates duration of JNK activity."
      Kadoya T., Khurana A., Tcherpakov M., Bromberg K.D., Didier C., Broday L., Asahara T., Bhoumik A., Ronai Z.
      Mol. Cell. Biol. 25:8619-8630(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH JAMP.
    12. "JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length."
      Tararuk T., Ostman N., Li W., Bjorkblom B., Padzik A., Zdrojewska J., Hongisto V., Herdegen T., Konopka W., Courtney M.J., Coffey E.T.
      J. Cell Biol. 173:265-277(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
    13. "JNK-mediated turnover and stabilization of the transcription factor p45/NF-E2 during differentiation of murine erythroleukemia cells."
      Lee T.L., Shyu Y.C., Hsu P.H., Chang C.W., Wen S.C., Hsiao W.Y., Tsai M.D., Shen C.K.
      Proc. Natl. Acad. Sci. U.S.A. 107:52-57(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NFE2, FUNCTION.
    14. Cited for: FUNCTION, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiMK08_MOUSE
    AccessioniPrimary (citable) accession number: Q91Y86
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2002
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 141 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. 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