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P53778

- MK12_HUMAN

UniProt

P53778 - MK12_HUMAN

Protein

Mitogen-activated protein kinase 12

Gene

MAPK12

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 163 (01 Oct 2014)
      Sequence version 3 (15 Jul 1998)
      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.7 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Binds 2 magnesium ions.1 Publication

    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.2 Publications

    Kineticsi

    1. KM=37 µM for ATP1 Publication
    2. KM=313 µM for EGFR substrate peptide1 Publication
    3. KM=254 µM for GST-ATF21 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: UniProtKB
    3. MAP kinase activity Source: ProtInc
    4. protein binding Source: UniProtKB
    5. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell cycle arrest Source: ProtInc
    2. DNA damage induced protein phosphorylation Source: ProtInc
    3. muscle cell differentiation Source: Reactome
    4. muscle organ development Source: ProtInc
    5. myoblast differentiation Source: UniProtKB
    6. neurotrophin TRK receptor signaling pathway Source: Reactome
    7. peptidyl-serine phosphorylation Source: BHF-UCL
    8. positive regulation of muscle cell differentiation Source: Reactome
    9. Ras protein signal transduction Source: Reactome
    10. regulation of transcription, DNA-templated Source: UniProtKB-KW
    11. signal transduction Source: ProtInc
    12. 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_12065. p38MAPK events.
    REACT_200686. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_21402. CDO in myogenesis.
    REACT_25299. DSCAM interactions.
    REACT_75776. NOD1/2 Signaling Pathway.
    SignaLinkiP53778.

    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:ERK6, SAPK3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:6874. MAPK12.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. mitochondrion Source: UniProtKB-SubCell
    4. nucleoplasm Source: Reactome
    5. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi179 – 1791D → A: Emulation of the active state. 2 Publications
    Mutagenesisi185 – 1851Y → F: Loss of activity. 2 Publications
    Mutagenesisi330 – 3301F → S: No effect. 2 Publications

    Organism-specific databases

    PharmGKBiPA30619.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 367367Mitogen-activated protein kinase 12PRO_0000186282Add
    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.2 Publications
    Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP53778.
    PaxDbiP53778.
    PRIDEiP53778.

    PTM databases

    PhosphoSiteiP53778.

    Expressioni

    Tissue specificityi

    Highly expressed in skeletal muscle and heart.2 Publications

    Inductioni

    Expression of MAPK12 is down-regulation by MAPK14 activation.1 Publication

    Gene expression databases

    ArrayExpressiP53778.
    BgeeiP53778.
    CleanExiHS_MAPK12.
    GenevestigatoriP53778.

    Organism-specific databases

    HPAiCAB025483.
    HPA018841.
    HPA054562.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PKN1Q165122EBI-602406,EBI-602382

    Protein-protein interaction databases

    BioGridi112207. 19 interactions.
    IntActiP53778. 9 interactions.
    MINTiMINT-90266.
    STRINGi9606.ENSP00000215659.

    Structurei

    Secondary structure

    1
    367
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi17 – 215
    Beta strandi24 – 329
    Beta strandi41 – 466
    Turni47 – 493
    Beta strandi52 – 576
    Helixi65 – 8016
    Beta strandi90 – 934
    Turni99 – 1013
    Beta strandi106 – 1105
    Beta strandi113 – 1153
    Helixi116 – 1227
    Helixi127 – 14620
    Helixi156 – 1583
    Beta strandi159 – 1613
    Beta strandi167 – 1693
    Helixi189 – 1913
    Helixi195 – 1984
    Turni199 – 2013
    Helixi207 – 22115
    Helixi231 – 24212
    Helixi247 – 2515
    Helixi256 – 2649
    Helixi273 – 2753
    Helixi282 – 29110
    Turni296 – 2983
    Helixi302 – 3076
    Helixi309 – 3113
    Turni312 – 3143
    Helixi337 – 34913

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CM8X-ray2.40A/B1-367[»]
    ProteinModelPortaliP53778.
    SMRiP53778. Positions 8-353.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP53778.

    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.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP53778.
    KOiK04441.
    OMAiWEVRERY.
    PhylomeDBiP53778.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P53778-1) [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

    MSSPPPARSG FYRQEVTKTA WEVRAVYRDL QPVGSGAYGA VCSAVDGRTG    50
    AKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD 100
    DFTDFYLVMP FMGTDLGKLM KHEKLGEDRI QFLVYQMLKG LRYIHAAGII 150
    HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW 200
    MRYTQTVDIW SVGCIMAEMI TGKTLFKGSD HLDQLKEIMK VTGTPPAEFV 250
    QRLQSDEAKN YMKGLPELEK KDFASILTNA SPLAVNLLEK MLVLDAEQRV 300
    TAGEALAHPY FESLHDTEDE PQVQKYDDSF DDVDRTLDEW KRVTYKEVLS 350
    FKPPRQLGAR VSKETPL 367
    Length:367
    Mass (Da):41,940
    Last modified:July 15, 1998 - v3
    Checksum:iEF680401D8E40610
    GO
    Isoform 2 (identifier: P53778-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         142-151: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:357
    Mass (Da):40,808
    Checksum:i35F0C4A10EB77B20
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti7 – 71A → T in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti70 – 701R → L in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti138 – 1381L → M in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti201 – 2022MR → IA in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti261 – 2611Y → N in AAB40118. (PubMed:8920915)Curated
    Sequence conflicti297 – 2982EQ → DI in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti300 – 3001V → L in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti305 – 3051A → F in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti307 – 3071A → S in CAA55984. (PubMed:8633070)Curated
    Sequence conflicti332 – 3332DV → YF in CAA55984. (PubMed:8633070)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti103 – 1031T → M.2 Publications
    Corresponds to variant rs34422484 [ dbSNP | Ensembl ].
    VAR_042265
    Natural varianti230 – 2301D → N.1 Publication
    Corresponds to variant rs35396905 [ dbSNP | Ensembl ].
    VAR_042266
    Natural varianti244 – 2441T → M.
    Corresponds to variant rs2066776 [ dbSNP | Ensembl ].
    VAR_012002

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei142 – 15110Missing in isoform 2. 1 PublicationVSP_055224

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X79483 mRNA. Translation: CAA55984.1.
    Y10487 mRNA. Translation: CAA71511.1.
    U66243 mRNA. Translation: AAB40118.1.
    CR456515 mRNA. Translation: CAG30401.1.
    AL022328 Genomic DNA. No translation available.
    BC015741 mRNA. Translation: AAH15741.1.
    CCDSiCCDS14089.1. [P53778-1]
    PIRiJC5252.
    JC6138.
    RefSeqiNP_002960.2. NM_002969.3.
    UniGeneiHs.432642.

    Genome annotation databases

    EnsembliENST00000215659; ENSP00000215659; ENSG00000188130. [P53778-1]
    GeneIDi6300.
    KEGGihsa:6300.
    UCSCiuc003bkm.1. human. [P53778-1]

    Polymorphism databases

    DMDMi2851522.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X79483 mRNA. Translation: CAA55984.1 .
    Y10487 mRNA. Translation: CAA71511.1 .
    U66243 mRNA. Translation: AAB40118.1 .
    CR456515 mRNA. Translation: CAG30401.1 .
    AL022328 Genomic DNA. No translation available.
    BC015741 mRNA. Translation: AAH15741.1 .
    CCDSi CCDS14089.1. [P53778-1 ]
    PIRi JC5252.
    JC6138.
    RefSeqi NP_002960.2. NM_002969.3.
    UniGenei Hs.432642.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CM8 X-ray 2.40 A/B 1-367 [» ]
    ProteinModelPortali P53778.
    SMRi P53778. Positions 8-353.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112207. 19 interactions.
    IntActi P53778. 9 interactions.
    MINTi MINT-90266.
    STRINGi 9606.ENSP00000215659.

    Chemistry

    BindingDBi P53778.
    ChEMBLi CHEMBL2094115.
    GuidetoPHARMACOLOGYi 1501.

    PTM databases

    PhosphoSitei P53778.

    Polymorphism databases

    DMDMi 2851522.

    Proteomic databases

    MaxQBi P53778.
    PaxDbi P53778.
    PRIDEi P53778.

    Protocols and materials databases

    DNASUi 6300.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000215659 ; ENSP00000215659 ; ENSG00000188130 . [P53778-1 ]
    GeneIDi 6300.
    KEGGi hsa:6300.
    UCSCi uc003bkm.1. human. [P53778-1 ]

    Organism-specific databases

    CTDi 6300.
    GeneCardsi GC22M050684.
    HGNCi HGNC:6874. MAPK12.
    HPAi CAB025483.
    HPA018841.
    HPA054562.
    MIMi 602399. gene.
    neXtProti NX_P53778.
    PharmGKBi PA30619.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P53778.
    KOi K04441.
    OMAi WEVRERY.
    PhylomeDBi P53778.
    TreeFami TF105100.

    Enzyme and pathway databases

    Reactomei REACT_12065. p38MAPK events.
    REACT_200686. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_21402. CDO in myogenesis.
    REACT_25299. DSCAM interactions.
    REACT_75776. NOD1/2 Signaling Pathway.
    SignaLinki P53778.

    Miscellaneous databases

    EvolutionaryTracei P53778.
    GeneWikii MAPK12.
    GenomeRNAii 6300.
    NextBioi 24459.
    PROi P53778.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P53778.
    Bgeei P53778.
    CleanExi HS_MAPK12.
    Genevestigatori P53778.

    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. "ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation."
      Lechner C., Zahalka M.A., Giot J.-F., Moeller N.P.H., Ullrich A.
      Proc. Natl. Acad. Sci. U.S.A. 93:4355-4359(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF TYR-185.
      Tissue: Skeletal muscle.
    2. "Assignment of the human stress-activated protein kinase-3 gene (SAPK3) to chromosome 22q13.3 by fluorescence in situ hybridization."
      Goedert M., Hasegawa J., Craxton M., Leversha M.A., Clegg S.
      Genomics 41:501-502(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Skeletal muscle.
    3. "The primary structure of p38 gamma: a new member of p38 group of MAP kinases."
      Li Z., Jiang Y., Ulevitch R.J., Han J.
      Biochem. Biophys. Res. Commun. 228:334-340(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT MET-103.
    5. "The DNA sequence of human chromosome 22."
      Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
      , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
      Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM 1).
      Tissue: Pancreas.
    7. "Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6."
      Enslen H., Raingeaud J., Davis R.J.
      J. Biol. Chem. 273:1741-1748(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF ATF2; ELK1 AND MBP, ENZYME REGULATION.
    8. "Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition."
      Hasegawa M., Cuenda A., Spillantini M.G., Thomas G.M., Buee-Scherrer V., Cohen P., Goedert M.
      J. Biol. Chem. 274:12626-12631(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SNTA1, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
    9. "Differential activation of p38 mitogen-activated protein kinase isoforms depending on signal strength."
      Alonso G., Ambrosino C., Jones M., Nebreda A.R.
      J. Biol. Chem. 275:40641-40648(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP2K6/MKK6.
    10. "Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest."
      Wang X., McGowan C.H., Zhao M., He L., Downey J.S., Fearns C., Wang Y., Huang S., Han J.
      Mol. Cell. Biol. 20:4543-4552(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REGULATION OF THE G2 CHECKPOINT.
    11. "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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Heart.
    12. "A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria."
      Wiltshire C., Matsushita M., Tsukada S., Gillespie D.A., May G.H.
      Biochem. J. 367:577-585(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS, SUBCELLULAR LOCATION, INTERACTION WITH SH3BP5.
    13. "p38gamma MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle."
      Ho R.C., Alcazar O., Fujii N., Hirshman M.F., Goodyear L.J.
      Am. J. Physiol. 286:R342-R349(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Active mutants of the human p38alpha mitogen-activated protein kinase."
      Diskin R., Askari N., Capone R., Engelberg D., Livnah O.
      J. Biol. Chem. 279:47040-47049(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASP-179 AND PHE-330.
    15. "p38alpha antagonizes p38gamma activity through c-Jun-dependent ubiquitin-proteasome pathways in regulating Ras transformation and stress response."
      Qi X., Pohl N.M., Loesch M., Hou S., Li R., Qin J.Z., Cuenda A., Chen G.
      J. Biol. Chem. 282:31398-31408(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, UBIQUITINATION.
    16. "p38gamma regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock."
      Sabio G., Cerezo-Guisado M.I., Del Reino P., Inesta-Vaquera F.A., Rousseau S., Arthur J.S., Campbell D.G., Centeno F., Cuenda A.
      J. Cell Sci. 123:2596-2604(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF DLG1.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Loss of p38gamma MAPK induces pleiotropic mitotic defects and massive cell death."
      Kukkonen-Macchi A., Sicora O., Kaczynska K., Oetken-Lindholm C., Pouwels J., Laine L., Kallio M.J.
      J. Cell Sci. 124:216-227(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    19. "p38gamma mitogen-activated protein kinase contributes to oncogenic properties maintenance and resistance to poly (ADP-ribose)-polymerase-1 inhibition in breast cancer."
      Meng F., Zhang H., Liu G., Kreike B., Chen W., Sethi S., Miller F.R., Wu G.
      Neoplasia 13:472-482(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CANCER.
    20. "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.
    21. "The structure of phosphorylated p38gamma is monomeric and reveals a conserved activation-loop conformation."
      Bellon S., Fitzgibbon M.J., Fox T., Hsiao H.M., Wilson K.P.
      Structure 7:1057-1065(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), COFACTOR, SUBUNIT.
    22. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-103 AND ASN-230.

    Entry informationi

    Entry nameiMK12_HUMAN
    AccessioniPrimary (citable) accession number: P53778
    Secondary accession number(s): Q14260
    , Q6IC53, Q99588, Q99672
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: July 15, 1998
    Last modified: October 1, 2014
    This is version 163 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3