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O08911

- MK12_MOUSE

UniProt

O08911 - MK12_MOUSE

Protein

Mitogen-activated protein kinase 12

Gene

Mapk12

Organism
Mus musculus (Mouse)
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 Jul 1997)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 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. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration.3 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Binds 2 magnesium ions.

    Enzyme regulationi

    Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei56 – 561ATPPROSITE-ProRule annotation
    Active sitei153 – 1531Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi33 – 419ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. magnesium ion binding Source: Ensembl
    3. MAP kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. myoblast differentiation Source: Ensembl
    3. negative regulation of cell cycle Source: Ensembl
    4. peptidyl-serine phosphorylation Source: Ensembl
    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, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_207601. p38MAPK events.
    REACT_211125. NOD1/2 Signaling Pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 12 (EC:2.7.11.24)
    Short name:
    MAP kinase 12
    Short name:
    MAPK 12
    Alternative name(s):
    Extracellular signal-regulated kinase 6
    Short name:
    ERK-6
    Mitogen-activated protein kinase p38 gamma
    Short name:
    MAP kinase p38 gamma
    Stress-activated protein kinase 3
    Gene namesi
    Name:Mapk12
    Synonyms:Sapk3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:1353438. Mapk12.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Mitochondrion By similarity
    Note: Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma.By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 367367Mitogen-activated protein kinase 12PRO_0000186283Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei183 – 1831Phosphothreonine; by MAP2K3 and MAP2K6By similarity
    Modified residuei185 – 1851Phosphotyrosine; by MAP2K3 and MAP2K6By similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.1 Publication
    Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO08911.
    PaxDbiO08911.
    PRIDEiO08911.

    PTM databases

    PhosphoSiteiO08911.

    Expressioni

    Tissue specificityi

    Highly expressed in skeletal muscle. Also expressed in the heart, particularly in cardiac myocytes, lung, thymus and testes.1 Publication

    Gene expression databases

    ArrayExpressiO08911.
    BgeeiO08911.
    CleanExiMM_MAPK12.
    GenevestigatoriO08911.

    Interactioni

    Subunit structurei

    Monomer. Interacts with the PDZ domain of the syntrophin SNTA1 By similarity. Interacts with SH3BP5, LIN7C, SCRIB and SYNJ2BP By similarity.By similarity

    Protein-protein interaction databases

    IntActiO08911. 1 interaction.
    MINTiMINT-1550872.
    STRINGi10090.ENSMUSP00000086207.

    Structurei

    3D structure databases

    ProteinModelPortaliO08911.
    SMRiO08911. Positions 8-353.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 311285Protein 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.
    GeneTreeiENSGT00680000099969.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiO08911.
    KOiK04441.
    OMAiNFKPPQT.
    OrthoDBiEOG7PCJGV.
    PhylomeDBiO08911.
    TreeFamiTF105100.

    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.

    O08911-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSSPPPARKG FYRQEVTKTA WEVRAVYQDL QPVGSGAYGA VCSAVDSRTG    50
    NKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDESLD 100
    DFTDFYLVMP FMGTDLGKLM KHETLSEDRI QFLVYQMLKG LKYIHAAGVI 150
    HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW 200
    MRYTQTVDIW SVGCIMAEMI TGKILFKGND HLDQLKEIMK ITGTPPPEFV 250
    QKLQSAEAKN YMEGLPELEK KDFASVLTNA SPQAVNLLER MLVLDAEQRV 300
    TAAEALTHPY FESLRDTEDE PKAQKYDDSF DDVDRTLEEW KRVTYKEVLS 350
    FKPPRQLGAR VPKETAL 367
    Length:367
    Mass (Da):42,043
    Last modified:July 1, 1997 - v1
    Checksum:iAB36A40EF3C59981
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y13439 mRNA. Translation: CAA73850.1.
    AK011286 mRNA. No translation available.
    BC021640 mRNA. Translation: AAH21640.1.
    CCDSiCCDS27740.1.
    RefSeqiNP_038899.1. NM_013871.3.
    UniGeneiMm.38343.

    Genome annotation databases

    EnsembliENSMUST00000088827; ENSMUSP00000086207; ENSMUSG00000022610.
    GeneIDi29857.
    KEGGimmu:29857.
    UCSCiuc007xfl.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y13439 mRNA. Translation: CAA73850.1 .
    AK011286 mRNA. No translation available.
    BC021640 mRNA. Translation: AAH21640.1 .
    CCDSi CCDS27740.1.
    RefSeqi NP_038899.1. NM_013871.3.
    UniGenei Mm.38343.

    3D structure databases

    ProteinModelPortali O08911.
    SMRi O08911. Positions 8-353.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O08911. 1 interaction.
    MINTi MINT-1550872.
    STRINGi 10090.ENSMUSP00000086207.

    Chemistry

    BindingDBi O08911.
    ChEMBLi CHEMBL2111473.

    PTM databases

    PhosphoSitei O08911.

    Proteomic databases

    MaxQBi O08911.
    PaxDbi O08911.
    PRIDEi O08911.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000088827 ; ENSMUSP00000086207 ; ENSMUSG00000022610 .
    GeneIDi 29857.
    KEGGi mmu:29857.
    UCSCi uc007xfl.2. mouse.

    Organism-specific databases

    CTDi 6300.
    MGIi MGI:1353438. Mapk12.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00680000099969.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi O08911.
    KOi K04441.
    OMAi NFKPPQT.
    OrthoDBi EOG7PCJGV.
    PhylomeDBi O08911.
    TreeFami TF105100.

    Enzyme and pathway databases

    Reactomei REACT_205688. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_207601. p38MAPK events.
    REACT_211125. NOD1/2 Signaling Pathway.

    Miscellaneous databases

    NextBioi 307054.
    PROi O08911.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O08911.
    Bgeei O08911.
    CleanExi MM_MAPK12.
    Genevestigatori O08911.

    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. Goedert M., Craxton M.
      Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Skeletal muscle.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Embryo.
    3. "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].
      Strain: FVB/N.
    4. "Cardiac expression and subcellular localization of the p38 mitogen-activated protein kinase member, stress-activated protein kinase-3 (SAPK3)."
      Court N.W., dos Remedios C.G., Cordell J., Bogoyevitch M.A.
      J. Mol. Cell. Cardiol. 34:413-426(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    5. "p38-{gamma}-dependent gene silencing restricts entry into the myogenic differentiation program."
      Gillespie M.A., Le Grand F., Scime A., Kuang S., von Maltzahn J., Seale V., Cuenda A., Ranish J.A., Rudnicki M.A.
      J. Cell Biol. 187:991-1005(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. Cited for: PHOSPHORYLATION, ENZYME REGULATION.
    7. "p38gamma regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage."
      Wu C.C., Wu X., Han J., Sun P.
      Protein Cell 1:573-583(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Evidence of p38gamma and p38delta involvement in cell transformation processes."
      Cerezo-Guisado M.I., del Reino P., Remy G., Kuma Y., Arthur J.S., Gallego-Ortega D., Cuenda A.
      Carcinogenesis 32:1093-1099(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "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 nameiMK12_MOUSE
    AccessioniPrimary (citable) accession number: O08911
    Secondary accession number(s): Q9D0M4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 1, 1997
    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, 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