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Q66H84

- MAPK3_RAT

UniProt

Q66H84 - MAPK3_RAT

Protein

MAP kinase-activated protein kinase 3

Gene

Mapkapk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 1 (11 Oct 2004)
      Previous versions | rss
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    Functioni

    Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei75 – 751ATPPROSITE-ProRule annotation
    Active sitei168 – 1681Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi52 – 609ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. macropinocytosis Source: UniProtKB
    2. peptidyl-serine phosphorylation Source: Ensembl
    3. response to cytokine Source: UniProtKB
    4. response to lipopolysaccharide Source: UniProtKB
    5. toll-like receptor signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_203770. Oxidative Stress Induced Senescence.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    MAP kinase-activated protein kinase 3 (EC:2.7.11.1)
    Short name:
    MAPK-activated protein kinase 3
    Short name:
    MAPKAP kinase 3
    Short name:
    MAPKAP-K3
    Short name:
    MAPKAPK-3
    Short name:
    MK-3
    Gene namesi
    Name:Mapkapk3
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 8

    Organism-specific databases

    RGDi1304980. Mapkapk3.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity
    Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 384384MAP kinase-activated protein kinase 3PRO_0000086295Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei203 – 2031Phosphothreonine; by MAPK14By similarity
    Modified residuei253 – 2531Phosphoserine; by MAPK14By similarity
    Modified residuei309 – 3091Phosphoserine; by autocatalysisBy similarity
    Modified residuei315 – 3151Phosphothreonine; by MAPK14By similarity

    Post-translational modificationi

    Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-203, Ser-253 and Thr-315.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiQ66H84.
    PRIDEiQ66H84.

    PTM databases

    PhosphoSiteiQ66H84.

    Expressioni

    Gene expression databases

    GenevestigatoriQ66H84.

    Interactioni

    Subunit structurei

    Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000020065.

    Structurei

    3D structure databases

    ProteinModelPortaliQ66H84.
    SMRiQ66H84. Positions 37-370.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini46 – 306261Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni309 – 34537Autoinhibitory helixBy similarityAdd
    BLAST
    Regioni347 – 37125p38 MAPK-binding siteBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi337 – 34610Nuclear export signal (NES)By similarity
    Motifi352 – 3554Bipartite nuclear localization signal 1By similarity
    Motifi366 – 3705Bipartite nuclear localization signal 2By similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110339.
    HOGENOMiHOG000233031.
    HOVERGENiHBG106948.
    InParanoidiQ66H84.
    KOiK04444.
    OMAiIRMGQYG.
    OrthoDBiEOG786H3M.
    PhylomeDBiQ66H84.
    TreeFamiTF312891.

    Family and domain databases

    Gene3Di4.10.1170.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR027442. MAPKAPK_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q66H84-1 [UniParc]FASTAAdd to Basket

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    MDGETAGEKG SLVPQPGALG APALGGAPAP GVRREPKKYA VTDDYQLSKQ    50
    VLGLGVNGKV LECYHRRSGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV 100
    RILDVYENMH HGKRCLLIVM ECMEGGELFS RIQERGDQAF TEREAAEIMR 150
    DIGTAIQFLH SQNIAHRDVK PENLLYTSKE KDAVLKLTDF GFAKETTQNA 200
    LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG FPPFYSNTGQ 250
    AISPGMKRRI RLGQYGFPKP EWADVSEDAK QLIRLLLKTD PTERLTIMQF 300
    MNHPWINQSM EVPQTPLHTA RVLEEDKDHW DDVKEEMTSA LATMRVDYDQ 350
    VKIKDLKTSN NRLLNKRRKK QGGSSSASPG CNNQ 384
    Length:384
    Mass (Da):43,222
    Last modified:October 11, 2004 - v1
    Checksum:iE094358C901F7E70
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC081974 mRNA. Translation: AAH81974.1.
    RefSeqiNP_001012127.1. NM_001012127.1.
    XP_006243838.1. XM_006243776.1.
    UniGeneiRn.8789.

    Genome annotation databases

    EnsembliENSRNOT00000020065; ENSRNOP00000020065; ENSRNOG00000014832.
    GeneIDi315994.
    KEGGirno:315994.
    UCSCiRGD:1304980. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC081974 mRNA. Translation: AAH81974.1 .
    RefSeqi NP_001012127.1. NM_001012127.1.
    XP_006243838.1. XM_006243776.1.
    UniGenei Rn.8789.

    3D structure databases

    ProteinModelPortali Q66H84.
    SMRi Q66H84. Positions 37-370.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000020065.

    PTM databases

    PhosphoSitei Q66H84.

    Proteomic databases

    PaxDbi Q66H84.
    PRIDEi Q66H84.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000020065 ; ENSRNOP00000020065 ; ENSRNOG00000014832 .
    GeneIDi 315994.
    KEGGi rno:315994.
    UCSCi RGD:1304980. rat.

    Organism-specific databases

    CTDi 7867.
    RGDi 1304980. Mapkapk3.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110339.
    HOGENOMi HOG000233031.
    HOVERGENi HBG106948.
    InParanoidi Q66H84.
    KOi K04444.
    OMAi IRMGQYG.
    OrthoDBi EOG786H3M.
    PhylomeDBi Q66H84.
    TreeFami TF312891.

    Enzyme and pathway databases

    Reactomei REACT_203770. Oxidative Stress Induced Senescence.

    Miscellaneous databases

    NextBioi 670215.
    PROi Q66H84.

    Gene expression databases

    Genevestigatori Q66H84.

    Family and domain databases

    Gene3Di 4.10.1170.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR027442. MAPKAPK_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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: Kidney.

    Entry informationi

    Entry nameiMAPK3_RAT
    AccessioniPrimary (citable) accession number: Q66H84
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 6, 2005
    Last sequence update: October 11, 2004
    Last modified: October 1, 2014
    This is version 90 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