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Protein

Mitogen-activated protein kinase 12

Gene

MAPK12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Mg2+1 PublicationNote: 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

    • ATP binding Source: UniProtKB-KW
    • magnesium ion binding Source: UniProtKB
    • MAP kinase activity Source: ProtInc
    • protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    • cell cycle arrest Source: ProtInc
    • DNA damage induced protein phosphorylation Source: ProtInc
    • MAPK cascade Source: GOC
    • mitochondrion organization Source: Reactome
    • muscle cell differentiation Source: Reactome
    • muscle organ development Source: ProtInc
    • myoblast differentiation Source: UniProtKB
    • neurotrophin TRK receptor signaling pathway Source: Reactome
    • organelle organization Source: Reactome
    • peptidyl-serine phosphorylation Source: BHF-UCL
    • positive regulation of muscle cell differentiation Source: Reactome
    • positive regulation of peptidase activity Source: ParkinsonsUK-UCL
    • Ras protein signal transduction Source: Reactome
    • regulation of transcription, DNA-templated Source: UniProtKB-KW
    • signal transduction Source: ProtInc
    • transcription, DNA-templated Source: UniProtKB-KW
    • vascular endothelial growth factor receptor signaling pathway Source: Reactome
    Complete GO annotation...

    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

    BRENDAi2.7.11.24. 2681.
    ReactomeiREACT_12065. p38MAPK events.
    REACT_21402. CDO in myogenesis.
    REACT_25299. DSCAM interactions.
    REACT_264464. VEGFA-VEGFR2 Pathway.
    REACT_264544. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    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 Componenti: 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

    Complete GO annotation...

    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. 1 Publication
    Mutagenesisi185 – 1851Y → F: Loss of activity. 1 Publication
    Mutagenesisi330 – 3301F → S: No effect. 1 Publication

    Organism-specific databases

    PharmGKBiPA30619.

    Polymorphism and mutation databases

    BioMutaiMAPK12.
    DMDMi2851522.

    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

    BgeeiP53778.
    CleanExiHS_MAPK12.
    ExpressionAtlasiP53778. baseline and differential.
    GenevestigatoriP53778.

    Organism-specific databases

    HPAiCAB025483.
    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
    PTPN4P290742EBI-602406,EBI-710431
    SIAH1Q8IUQ43EBI-602406,EBI-747107

    Protein-protein interaction databases

    BioGridi112207. 22 interactions.
    IntActiP53778. 12 interactions.
    MINTiMINT-90266.
    STRINGi9606.ENSP00000215659.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CM8X-ray2.40A/B1-367[»]
    4QUMX-ray2.52B182-190[»]
    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.
    GeneTreeiENSGT00550000074271.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP53778.
    KOiK04441.
    OMAiPTAQKYD.
    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.
    [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. AlignAdd to basket

    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

            10         20         30         40         50
    MSSPPPARSG FYRQEVTKTA WEVRAVYRDL QPVGSGAYGA VCSAVDGRTG
    60 70 80 90 100
    AKVAIKKLYR PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD
    110 120 130 140 150
    DFTDFYLVMP FMGTDLGKLM KHEKLGEDRI QFLVYQMLKG LRYIHAAGII
    160 170 180 190 200
    HRDLKPGNLA VNEDCELKIL DFGLARQADS EMTGYVVTRW YRAPEVILNW
    210 220 230 240 250
    MRYTQTVDIW SVGCIMAEMI TGKTLFKGSD HLDQLKEIMK VTGTPPAEFV
    260 270 280 290 300
    QRLQSDEAKN YMKGLPELEK KDFASILTNA SPLAVNLLEK MLVLDAEQRV
    310 320 330 340 350
    TAGEALAHPY FESLHDTEDE PQVQKYDDSF DDVDRTLDEW KRVTYKEVLS
    360
    FKPPRQLGAR VSKETPL
    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:
    EMBLi
    GenBanki
    DDBJi
    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_001290181.1. NM_001303252.1. [P53778-2]
    NP_002960.2. NM_002969.4. [P53778-1]
    UniGeneiHs.432642.

    Genome annotation databases

    EnsembliENST00000215659; ENSP00000215659; ENSG00000188130. [P53778-1]
    ENST00000622558; ENSP00000479972; ENSG00000188130. [P53778-2]
    GeneIDi6300.
    KEGGihsa:6300.
    UCSCiuc003bkm.1. human. [P53778-1]

    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:
    EMBLi
    GenBanki
    DDBJi
    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_001290181.1. NM_001303252.1. [P53778-2]
    NP_002960.2. NM_002969.4. [P53778-1]
    UniGeneiHs.432642.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CM8X-ray2.40A/B1-367[»]
    4QUMX-ray2.52B182-190[»]
    ProteinModelPortaliP53778.
    SMRiP53778. Positions 8-353.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112207. 22 interactions.
    IntActiP53778. 12 interactions.
    MINTiMINT-90266.
    STRINGi9606.ENSP00000215659.

    Chemistry

    BindingDBiP53778.
    ChEMBLiCHEMBL2094115.
    GuidetoPHARMACOLOGYi1501.

    PTM databases

    PhosphoSiteiP53778.

    Polymorphism and mutation databases

    BioMutaiMAPK12.
    DMDMi2851522.

    Proteomic databases

    MaxQBiP53778.
    PaxDbiP53778.
    PRIDEiP53778.

    Protocols and materials databases

    DNASUi6300.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000215659; ENSP00000215659; ENSG00000188130. [P53778-1]
    ENST00000622558; ENSP00000479972; ENSG00000188130. [P53778-2]
    GeneIDi6300.
    KEGGihsa:6300.
    UCSCiuc003bkm.1. human. [P53778-1]

    Organism-specific databases

    CTDi6300.
    GeneCardsiGC22M050684.
    HGNCiHGNC:6874. MAPK12.
    HPAiCAB025483.
    HPA054562.
    MIMi602399. gene.
    neXtProtiNX_P53778.
    PharmGKBiPA30619.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00550000074271.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP53778.
    KOiK04441.
    OMAiPTAQKYD.
    PhylomeDBiP53778.
    TreeFamiTF105100.

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 2681.
    ReactomeiREACT_12065. p38MAPK events.
    REACT_21402. CDO in myogenesis.
    REACT_25299. DSCAM interactions.
    REACT_264464. VEGFA-VEGFR2 Pathway.
    REACT_264544. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
    REACT_75776. NOD1/2 Signaling Pathway.
    SignaLinkiP53778.

    Miscellaneous databases

    EvolutionaryTraceiP53778.
    GeneWikiiMAPK12.
    GenomeRNAii6300.
    NextBioi24459.
    PROiP53778.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP53778.
    CleanExiHS_MAPK12.
    ExpressionAtlasiP53778. baseline and differential.
    GenevestigatoriP53778.

    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.
    [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]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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: April 29, 2015
    This is version 170 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.