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P49187

- MK10_RAT

UniProt

P49187 - MK10_RAT

Protein

Mitogen-activated protein kinase 10

Gene

Mapk10

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (01 Nov 1997)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration 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 MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. 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 two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei93 – 931ATPPROSITE-ProRule annotation
    Active sitei189 – 1891Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi70 – 789ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: RGD
    2. JUN kinase activity Source: UniProtKB
    3. protein binding Source: IntAct

    GO - Biological processi

    1. JNK cascade Source: UniProtKB
    2. JUN phosphorylation Source: RGD
    3. protein phosphorylation 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.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 10 (EC:2.7.11.24)
    Short name:
    MAP kinase 10
    Short name:
    MAPK 10
    Alternative name(s):
    SAPK-beta
    Stress-activated protein kinase JNK3
    c-Jun N-terminal kinase 3
    p54-beta
    Gene namesi
    Name:Mapk10
    Synonyms:Jnk3, Prkm10
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3663. Mapk10.

    Subcellular locationi

    Cytoplasm. Membrane; Lipid-anchor. Nucleus. Mitochondrion
    Note: Palmitoylation regulates MAPK10 trafficking to cytoskeleton. Recruited to the mitochondria in the presence of SARM1.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. mitochondrion Source: UniProtKB
    3. nucleus Source: UniProtKB-SubCell
    4. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 464464Mitogen-activated protein kinase 10PRO_0000186279Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei154 – 1541S-nitrosocysteineBy similarity
    Modified residuei221 – 2211Phosphothreonine; by MAP2K7By similarity
    Modified residuei223 – 2231Phosphotyrosine; by MAP2K4By similarity
    Lipidationi462 – 4621S-palmitoyl cysteineBy similarity
    Lipidationi463 – 4631S-palmitoyl cysteineBy similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro By similarity.By similarity
    Palmitoylation regulates subcellular location and axonal development.By similarity

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein, S-nitrosylation

    Proteomic databases

    PaxDbiP49187.
    PRIDEiP49187.

    PTM databases

    PhosphoSiteiP49187.

    Expressioni

    Gene expression databases

    GenevestigatoriP49187.

    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 HDAC9 and MAPKBP1 By similarity. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. Interacts with SARM1 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Syt4P502322EBI-7155513,EBI-540118

    Protein-protein interaction databases

    IntActiP49187. 1 interaction.
    MINTiMINT-151503.

    Structurei

    3D structure databases

    ProteinModelPortaliP49187.
    SMRiP49187. Positions 45-400.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini64 – 359296Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi221 – 2233TXY

    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.
    InParanoidiP49187.
    KOiK04440.
    PhylomeDBiP49187.

    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.

    P49187-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLHFLYYCS EPTLDVKIAF CQGFDKHVDV SSVVKHYNMS KSKVDNQFYS    50
    VEVGDSTFTV LKRYQNLKPI GSGAQGIVCA AYDAVLDRNV AIKKLSRPFQ 100
    NQTHAKRAYR ELVLMKCVNH KNIISLLNVF TPQKTLEEFQ DVYLVMELMD 150
    ANLCQVIQME LDHERMSYLL YQMLSAIKHL HSAGIIHRDL KPSNIVVKSD 200
    CTLKILDFGL ARTAGTSFMM TPYVVTRYYR APEVILGMGY KENVDIWSVG 250
    CIMGEMVRHK ILFPGRDYID QWNKVIEQLG TPCPEFMKKL QPTVRNYVEN 300
    RPKYAGLTFP KLFPDSLFPA DSEHNKLKAS QARDLLSKML VIDPAKRISV 350
    DDALQHPYIN VWYDPAEVEA PPPQIYDKQL DEREHTIEEW KELIYKEVMN 400
    SEEKTKNGVV KGQPSPSGAA VNSSESLPPS SSVNDISSMS TDQTLASDTD 450
    SSLEASAGPL GCCR 464
    Length:464
    Mass (Da):52,530
    Last modified:November 1, 1997 - v2
    Checksum:i6D6279D7C3E68AF9
    GO

    Sequence cautioni

    The sequence AAA42110.1 differs from that shown. Reason: Frameshift at position 22.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27128 mRNA. Translation: AAA42110.1. Frameshift.
    PIRiS43969.
    RefSeqiNP_036938.2. NM_012806.2.
    UniGeneiRn.9911.

    Genome annotation databases

    GeneIDi25272.
    KEGGirno:25272.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L27128 mRNA. Translation: AAA42110.1 . Frameshift.
    PIRi S43969.
    RefSeqi NP_036938.2. NM_012806.2.
    UniGenei Rn.9911.

    3D structure databases

    ProteinModelPortali P49187.
    SMRi P49187. Positions 45-400.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P49187. 1 interaction.
    MINTi MINT-151503.

    Chemistry

    BindingDBi P49187.
    ChEMBLi CHEMBL4092.

    PTM databases

    PhosphoSitei P49187.

    Proteomic databases

    PaxDbi P49187.
    PRIDEi P49187.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25272.
    KEGGi rno:25272.

    Organism-specific databases

    CTDi 5602.
    RGDi 3663. Mapk10.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P49187.
    KOi K04440.
    PhylomeDBi P49187.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 5301.

    Miscellaneous databases

    NextBioi 605961.

    Gene expression databases

    Genevestigatori P49187.

    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].
      Tissue: Brain.
    2. Hulo-Demole C., Braconi-Quintaje S.
      Unpublished observations (MAR-1997)
      Cited for: IDENTIFICATION OF PROBABLE FRAMESHIFT.
    3. "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3."
      McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T., Davis R.J., Lefkowitz R.J.
      Science 290:1574-1577(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2.
    4. "JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons."
      Bruckner S.R., Estus S.
      J. Neurosci. Res. 70:665-670(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation."
      Kimberly W.T., Zheng J.B., Town T., Flavell R.A., Selkoe D.J.
      J. Neurosci. 25:5533-5543(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF APP.
    6. "The beta-arrestin-2 scaffold protein promotes c-Jun N-terminal kinase-3 activation by binding to its nonconserved N terminus."
      Guo C., Whitmarsh A.J.
      J. Biol. Chem. 283:15903-15911(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2.

    Entry informationi

    Entry nameiMK10_RAT
    AccessioniPrimary (citable) accession number: P49187
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 127 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3