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P52564

- MP2K6_HUMAN

UniProt

P52564 - MP2K6_HUMAN

Protein

Dual specificity mitogen-activated protein kinase kinase 6

Gene

MAP2K6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.8 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei14 – 152Cleavage; by anthrax lethal factor
    Binding sitei82 – 821ATPPROSITE-ProRule annotation
    Active sitei179 – 1791Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi59 – 679ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. MAP kinase kinase activity Source: ProtInc
    3. protein binding Source: UniProtKB
    4. protein kinase binding Source: UniProtKB
    5. protein serine/threonine kinase activity Source: UniProtKB-KW
    6. protein tyrosine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. activation of MAPK activity Source: Reactome
    2. apoptotic process Source: UniProtKB-KW
    3. cardiac muscle contraction Source: Ensembl
    4. cell cycle arrest Source: ProtInc
    5. cellular response to sorbitol Source: Ensembl
    6. DNA damage induced protein phosphorylation Source: ProtInc
    7. innate immune response Source: Reactome
    8. muscle cell differentiation Source: Reactome
    9. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    10. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    11. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
    12. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
    13. positive regulation of apoptotic process Source: Ensembl
    14. positive regulation of muscle cell differentiation Source: Reactome
    15. regulation of transcription, DNA-templated Source: UniProtKB-KW
    16. response to drug Source: Ensembl
    17. response to ischemia Source: Ensembl
    18. signal transduction Source: ProtInc
    19. stress-activated MAPK cascade Source: Reactome
    20. toll-like receptor 10 signaling pathway Source: Reactome
    21. toll-like receptor 2 signaling pathway Source: Reactome
    22. toll-like receptor 3 signaling pathway Source: Reactome
    23. toll-like receptor 4 signaling pathway Source: Reactome
    24. toll-like receptor 5 signaling pathway Source: Reactome
    25. toll-like receptor 9 signaling pathway Source: Reactome
    26. toll-like receptor signaling pathway Source: Reactome
    27. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    28. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    29. transcription, DNA-templated Source: UniProtKB-KW
    30. TRIF-dependent toll-like receptor signaling pathway Source: Reactome

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Apoptosis, Stress response, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.12.2. 2681.
    ReactomeiREACT_169436. Oxidative Stress Induced Senescence.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_21402. CDO in myogenesis.
    REACT_22442. Interleukin-1 signaling.
    REACT_75776. NOD1/2 Signaling Pathway.
    SignaLinkiP52564.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 6 (EC:2.7.12.2)
    Short name:
    MAP kinase kinase 6
    Short name:
    MAPKK 6
    Alternative name(s):
    MAPK/ERK kinase 6
    Short name:
    MEK 6
    Stress-activated protein kinase kinase 3
    Short name:
    SAPK kinase 3
    Short name:
    SAPKK-3
    Short name:
    SAPKK3
    Gene namesi
    Name:MAP2K6
    Synonyms:MEK6, MKK6, PRKMK6, SKK3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:6846. MAP2K6.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication. Cytoplasmcytoskeleton 1 Publication
    Note: Binds to microtubules.

    GO - Cellular componenti

    1. cytoskeleton Source: UniProtKB-SubCell
    2. cytosol Source: Reactome
    3. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi207 – 2071S → A: Inactivation.
    Mutagenesisi207 – 2071S → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.
    Mutagenesisi211 – 2111T → A: Inactivation.
    Mutagenesisi211 – 2111T → E: Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.

    Organism-specific databases

    PharmGKBiPA30591.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 334334Dual specificity mitogen-activated protein kinase kinase 6PRO_0000086386Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei207 – 2071O-acetylserine; by Yersinia yopJ; alternate1 Publication
    Modified residuei207 – 2071Phosphoserine; by MAP3K; alternate1 Publication
    Modified residuei211 – 2111O-acetylthreonine; by Yersinia yopJ; alternate1 Publication
    Modified residuei211 – 2111Phosphothreonine; by MAP3K; alternate1 Publication

    Post-translational modificationi

    Weakly autophosphorylated. Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.1 Publication
    Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP52564.
    PaxDbiP52564.
    PRIDEiP52564.

    PTM databases

    PhosphoSiteiP52564.

    Miscellaneous databases

    PMAP-CutDBP52564.

    Expressioni

    Tissue specificityi

    Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas.1 Publication

    Inductioni

    Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF.

    Gene expression databases

    ArrayExpressiP52564.
    BgeeiP52564.
    CleanExiHS_MAP2K6.
    GenevestigatoriP52564.

    Organism-specific databases

    HPAiCAB007744.
    HPA031134.

    Interactioni

    Subunit structurei

    Dimer. Interacts with Yersinia yopJ. Interacts (via its D domain) with its substrates MAPK11, MAPK12, MAPK13 and MAPK14 By similarity. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2 By similarity. Interacts with DCTN1. Interacts with EIF2AK2/PKR.By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GADD45AP245222EBI-448135,EBI-448167
    LRRK2Q5S0074EBI-448135,EBI-5323863
    MAP3K4Q9Y6R42EBI-448135,EBI-448104

    Protein-protein interaction databases

    BioGridi111594. 20 interactions.
    DIPiDIP-31346N.
    IntActiP52564. 11 interactions.
    MINTiMINT-3019559.
    STRINGi9606.ENSP00000351997.

    Structurei

    Secondary structure

    1
    334
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi50 – 523
    Beta strandi53 – 619
    Beta strandi63 – 7210
    Turni73 – 764
    Beta strandi77 – 848
    Helixi90 – 10415
    Turni110 – 1123
    Beta strandi115 – 1206
    Beta strandi122 – 1309
    Beta strandi133 – 1353
    Helixi136 – 14510
    Helixi152 – 17221
    Helixi182 – 1843
    Beta strandi185 – 1873
    Beta strandi193 – 1953
    Helixi201 – 2033
    Helixi207 – 2126
    Helixi222 – 2254
    Helixi236 – 25217
    Helixi263 – 27210
    Turni280 – 2823
    Helixi285 – 29410
    Helixi299 – 3013
    Helixi305 – 3084
    Helixi312 – 3198
    Helixi324 – 3329

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Y8OX-ray1.95B4-17[»]
    3ENMX-ray2.35A/B/C/D45-332[»]
    3FMEX-ray2.26A47-334[»]
    3VN9X-ray2.60A1-334[»]
    ProteinModelPortaliP52564.
    SMRiP52564. Positions 44-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP52564.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini53 – 314262Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni4 – 1916D domainBy similarityAdd
    BLAST
    Regioni311 – 33424DVD domainAdd
    BLAST

    Domaini

    The DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.1 Publication
    The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates.By similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000234206.
    HOVERGENiHBG108518.
    InParanoidiP52564.
    KOiK04433.
    OMAiESAVAMV.
    OrthoDBiEOG7J9VPW.
    PhylomeDBiP52564.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P52564-1) [UniParc]FASTAAdd to Basket

    Also known as: MKK6b

    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

    MSQSKGKKRN PGLKIPKEAF EQPQTSSTPP RDLDSKACIS IGNQNFEVKA    50
    DDLEPIMELG RGAYGVVEKM RHVPSGQIMA VKRIRATVNS QEQKRLLMDL 100
    DISMRTVDCP FTVTFYGALF REGDVWICME LMDTSLDKFY KQVIDKGQTI 150
    PEDILGKIAV SIVKALEHLH SKLSVIHRDV KPSNVLINAL GQVKMCDFGI 200
    SGYLVDSVAK TIDAGCKPYM APERINPELN QKGYSVKSDI WSLGITMIEL 250
    AILRFPYDSW GTPFQQLKQV VEEPSPQLPA DKFSAEFVDF TSQCLKKNSK 300
    ERPTYPELMQ HPFFTLHESK GTDVASFVKL ILGD 334
    Length:334
    Mass (Da):37,492
    Last modified:October 1, 1996 - v1
    Checksum:i4ECA8014522216AF
    GO
    Isoform 2 (identifier: P52564-2) [UniParc]FASTAAdd to Basket

    Also known as: MKK6

    The sequence of this isoform differs from the canonical sequence as follows:
         1-56: Missing.

    Show »
    Length:278
    Mass (Da):31,339
    Checksum:i1EE7FC1B26B11AE4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti125 – 1251V → M in AAB03705. (PubMed:8621675)Curated
    Sequence conflicti125 – 1251V → M in AAB03708. (PubMed:8621675)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5656Missing in isoform 2. 1 PublicationVSP_004882Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U39657 mRNA. Translation: AAC50389.1.
    U39656 mRNA. Translation: AAC50388.1.
    U49732 mRNA. Translation: AAB05035.1.
    U39065 mRNA. Translation: AAB03705.1.
    U39064 mRNA. Translation: AAB03708.1.
    D87905 mRNA. Translation: BAA13496.1.
    X96757 mRNA. Translation: CAA65532.1.
    BC012009 mRNA. Translation: AAH12009.1.
    CCDSiCCDS11686.1. [P52564-1]
    PIRiS71631.
    RefSeqiNP_002749.2. NM_002758.3. [P52564-1]
    UniGeneiHs.463978.

    Genome annotation databases

    EnsembliENST00000589647; ENSP00000467213; ENSG00000108984. [P52564-2]
    ENST00000590474; ENSP00000468348; ENSG00000108984. [P52564-1]
    GeneIDi5608.
    KEGGihsa:5608.
    UCSCiuc002jii.3. human. [P52564-1]

    Polymorphism databases

    DMDMi1709088.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U39657 mRNA. Translation: AAC50389.1 .
    U39656 mRNA. Translation: AAC50388.1 .
    U49732 mRNA. Translation: AAB05035.1 .
    U39065 mRNA. Translation: AAB03705.1 .
    U39064 mRNA. Translation: AAB03708.1 .
    D87905 mRNA. Translation: BAA13496.1 .
    X96757 mRNA. Translation: CAA65532.1 .
    BC012009 mRNA. Translation: AAH12009.1 .
    CCDSi CCDS11686.1. [P52564-1 ]
    PIRi S71631.
    RefSeqi NP_002749.2. NM_002758.3. [P52564-1 ]
    UniGenei Hs.463978.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2Y8O X-ray 1.95 B 4-17 [» ]
    3ENM X-ray 2.35 A/B/C/D 45-332 [» ]
    3FME X-ray 2.26 A 47-334 [» ]
    3VN9 X-ray 2.60 A 1-334 [» ]
    ProteinModelPortali P52564.
    SMRi P52564. Positions 44-334.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111594. 20 interactions.
    DIPi DIP-31346N.
    IntActi P52564. 11 interactions.
    MINTi MINT-3019559.
    STRINGi 9606.ENSP00000351997.

    Chemistry

    BindingDBi P52564.
    ChEMBLi CHEMBL2171.
    GuidetoPHARMACOLOGYi 2067.

    PTM databases

    PhosphoSitei P52564.

    Polymorphism databases

    DMDMi 1709088.

    Proteomic databases

    MaxQBi P52564.
    PaxDbi P52564.
    PRIDEi P52564.

    Protocols and materials databases

    DNASUi 5608.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000589647 ; ENSP00000467213 ; ENSG00000108984 . [P52564-2 ]
    ENST00000590474 ; ENSP00000468348 ; ENSG00000108984 . [P52564-1 ]
    GeneIDi 5608.
    KEGGi hsa:5608.
    UCSCi uc002jii.3. human. [P52564-1 ]

    Organism-specific databases

    CTDi 5608.
    GeneCardsi GC17P067410.
    HGNCi HGNC:6846. MAP2K6.
    HPAi CAB007744.
    HPA031134.
    MIMi 601254. gene.
    neXtProti NX_P52564.
    PharmGKBi PA30591.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000234206.
    HOVERGENi HBG108518.
    InParanoidi P52564.
    KOi K04433.
    OMAi ESAVAMV.
    OrthoDBi EOG7J9VPW.
    PhylomeDBi P52564.

    Enzyme and pathway databases

    BRENDAi 2.7.12.2. 2681.
    Reactomei REACT_169436. Oxidative Stress Induced Senescence.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_21402. CDO in myogenesis.
    REACT_22442. Interleukin-1 signaling.
    REACT_75776. NOD1/2 Signaling Pathway.
    SignaLinki P52564.

    Miscellaneous databases

    EvolutionaryTracei P52564.
    GeneWikii MAP2K6.
    GenomeRNAii 5608.
    NextBioi 21798.
    PMAP-CutDB P52564.
    PROi P52564.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P52564.
    Bgeei P52564.
    CleanExi HS_MAP2K6.
    Genevestigatori P52564.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    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. "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway."
      Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.
      Mol. Cell. Biol. 16:1247-1255(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS, FUNCTION.
      Tissue: Skeletal muscle.
    2. "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade."
      Stein B., Brady H., Yang M.X., Young D.B., Barbosa M.S.
      J. Biol. Chem. 271:11427-11433(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION.
      Tissue: T-cell.
    3. "Characterization of the structure and function of a novel MAP kinase kinase (MKK6)."
      Han J., Lee J.-D., Jiang Y., Li Z., Feng L., Ulevitch R.J.
      J. Biol. Chem. 271:2886-2891(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, MUTAGENESIS.
      Tissue: Placenta.
    4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION, ENZYME REGULATION, FUNCTION.
    5. "Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells."
      Cuenda A., Alonso G., Morrice N., Jones M., Meier R., Cohen P., Nebreda A.R.
      EMBO J. 15:4156-4164(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    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: Urinary bladder.
    7. "Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases."
      Goedert M., Cuenda A., Craxton M., Jakes R., Cohen P.
      EMBO J. 16:3563-3571(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ACTIVATION OF MAPK13.
    8. "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2."
      Ben-Levy R., Hooper S., Wilson R., Paterson H.F., Marshall C.J.
      Curr. Biol. 8:1049-1057(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    9. "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades."
      Chan-Hui P.Y., Weaver R.
      Biochem. J. 336:599-609(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K4.
    10. "MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases."
      Deacon K., Blank J.L.
      J. Biol. Chem. 274:16604-16610(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K2/MEKK2 AND MAP3K3/MEK3.
    11. "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain."
      Chen Z., Hutchison M., Cobb M.H.
      J. Biol. Chem. 274:28803-28807(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TAOK2, PHOSPHORYLATION BY TAOK2.
    12. "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway."
      Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.
      Nature 398:252-256(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K7/TAK1.
    13. "Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor."
      Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.
      Biochem. J. 352:739-745(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR.
    14. "Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity."
      Visconti R., Gadina M., Chiariello M., Chen E.H., Stancato L.F., Gutkind J.S., O'Shea J.J.
      Blood 96:1844-1852(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription."
      Bode J.G., Ludwig S., Freitas C.A., Schaper F., Ruhl M., Melmed S., Heinrich P.C., Haussinger D.
      Biol. Chem. 382:1447-1453(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    16. "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress."
      Morita K., Saitoh M., Tobiume K., Matsuura H., Enomoto S., Nishitoh H., Ichijo H.
      EMBO J. 20:6028-6036(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K5/ASK1.
    17. "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2."
      Chen Z., Cobb M.H.
      J. Biol. Chem. 276:16070-16075(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY TAOK2.
    18. "TAK1 is a ubiquitin-dependent kinase of MKK and IKK."
      Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J.
      Nature 412:346-351(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K7/TAK1.
    19. "Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation."
      Silva A.M., Whitmore M., Xu Z., Jiang Z., Li X., Williams B.R.
      J. Biol. Chem. 279:37670-37676(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EIF2AK2, PHOSPHORYLATION.
    20. "p150(Glued), Dynein, and microtubules are specifically required for activation of MKK3/6 and p38 MAPKs."
      Cheung P.Y., Zhang Y., Long J., Lin S., Zhang M., Jiang Y., Wu Z.
      J. Biol. Chem. 279:45308-45311(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DCTN1, MICROTUBULE-BINDING.
    21. "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase."
      Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.
      J. Biol. Chem. 280:3323-3330(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PAK6.
    22. "Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases."
      Takekawa M., Tatebayashi K., Saito H.
      Mol. Cell 18:295-306(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN.
    23. "Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation."
      Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K.
      Science 312:1211-1214(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT SER-207 AND THR-211, PHOSPHORYLATION AT SER-207 AND THR-211, INACTIVATION BY YERSINIA YOPJ, IDENTIFICATION BY MASS SPECTROMETRY.
    24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    25. "Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation."
      Sturchler E., Feurstein D., McDonald P., Duckett D.
      Biochemistry 49:4094-4102(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY MAP3K5/ASK1, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY.
    26. "MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases."
      Kim M.Y., Choi T.Y., Kim J.H., Lee J.H., Kim J.G., Sohn K.C., Yoon K.S., Kim C.D., Lee J.H., Yoon T.J.
      J. Dermatol. Sci. 60:114-119(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    27. Cited for: REVIEW ON ENZYME REGULATION, REVIEW ON FUNCTION.
    28. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    29. Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 45-332 OF MUTANT ASP-207 AND ASP-211, SUBUNIT.
    30. "Crystal structure of human mitogen-activated protein kinase kinase 6 (mek6) activated mutant (s207d, t211d)."
      Structural genomics consortium (SGC)
      Submitted (JUL-2011) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 47-334.

    Entry informationi

    Entry nameiMP2K6_HUMAN
    AccessioniPrimary (citable) accession number: P52564
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 150 of the entry and version 1 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 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3