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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

MAP2K6 Gene

protein-coding   GIFtS: 69
GCID: GC17P067410

Mitogen-Activated Protein Kinase Kinase 6


(Previous symbol: PRKMK6)
Alzheimer's & Parkinson's Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Mitogen-Activated Protein Kinase Kinase 61 2     SAPK Kinase 32 3
PRKMK61 2 3 5     EC 2.7.12.23 8
MEK62 3 5     MAPKK62 5
MKK62 3 5     Kinase 6 (MAP Kinase Kinase 6)1
Stress-Activated Protein Kinase Kinase 32 3     mitogen-activated1
SAPKK-32 3     Protein Kinase1
SAPKK32 3     Dual Specificity Mitogen-Activated Protein Kinase Kinase 62
MAPK/ERK Kinase 62 3     Protein Kinase, Mitogen-Activated, Kinase 6 (MAP Kinase Kinase 6)2
MAPKK 62 3     SKK33
MEK 62 3     MAP Kinase Kinase 63

External Ids:    HGNC: 68461   Entrez Gene: 56082   Ensembl: ENSG000001089847   OMIM: 6012545   UniProtKB: P525643   

Export aliases for MAP2K6 gene to outside databases

Previous GC identifers: GC17P067254 GC17P070371 GC17P067875 GC17P068007 GC17P064922 GC17P062796


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for MAP2K6 Gene:
This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated
protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an
integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in
response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated
signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle
arrest, transcription activation and apoptosis. (provided by RefSeq, Jul 2008)

GeneCards Summary for MAP2K6 Gene: 
MAP2K6 (mitogen-activated protein kinase kinase 6) is a protein-coding gene. Diseases associated with MAP2K6 include pierre robin sequence, and toxoplasmosis, and among its related super-pathways are Development FGF-family signaling and RANK Signaling in Osteoclasts. GO annotations related to this gene include protein serine/threonine kinase activity and protein tyrosine kinase activity. An important paralog of this gene is MAP2K3.

UniProtKB/Swiss-Prot: MP2K6_HUMAN, P52564
Function: 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

Gene Wiki entry for MAP2K6 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NT_010783.15  NC_018928.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the MAP2K6 gene promoter:
         ISGF-3   STAT1   ATF-2   Nkx2-5   CREB   deltaCREB   HSF2   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): MAP2K6 promoter sequence
   Search SABiosciences Chromatin IP Primers for MAP2K6

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat MAP2K6


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q24.3   Ensembl cytogenetic band:  17q24.3   HGNC cytogenetic band: 17q

MAP2K6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAP2K6 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P067410:  view genomic region     (about GC identifiers)

Start:
67,410,838 bp from pter      End:
67,539,472 bp from pter
Size:
128,635 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: MP2K6_HUMAN, P52564 (See protein sequence)
Recommended Name: Dual specificity mitogen-activated protein kinase kinase 6  
Size: 334 amino acids; 37492 Da
Subunit: 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
Subcellular location: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Binds to microtubules
4 PDB 3D structures from and Proteopedia for MAP2K6:
2Y8O (3D)        3ENM (3D)        3FME (3D)        3VN9 (3D)    
Alternative splicing: 2 isoforms:  P52564-1   P52564-2   

Explore the universe of human proteins at neXtProt for MAP2K6: NX_P52564

Explore proteomics data for MAP2K6 at MOPED 

Post-translational modifications:

  • UniProtKB: 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
  • UniProtKB: Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the
    MAPK signaling pathway
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P52564

  • 4/9 DME Specific Peptides for MAP2K6 (P52564) (see all 9)
     WICMELM  AILRFPY  TPPRDLDSKA  FYGALFREGD 

    MAP2K6 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    MAP2K6 Protein Expression
    REFSEQ proteins: NP_002749.2  
    ENSEMBL proteins: 
     ENSP00000468348   ENSP00000351997   ENSP00000466143   ENSP00000464916   ENSP00000467213  
    Reactome Protein details: P52564
    Human Recombinant Protein Products for MAP2K6: 
    EMD Millipore Purified and/or Recombinant MAP2K6 Protein
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    OriGene Protein Over-expression Lysate for MAP2K6
    OriGene MassSpec for MAP2K6 
    OriGene Custom Protein Services for MAP2K6
    GenScript Custom Purified and Recombinant Proteins Services for MAP2K6
    Novus Biologicals MAP2K6 Proteins
    Novus Biologicals MAP2K6 Lysates
    Sino Biological Recombinant Protein for MAP2K6
    Sino Biological Cell Lysate for MAP2K6 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for MAP2K6 

    Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005654nucleoplasm TAS--
    GO:0005829cytosol TAS--
    GO:0005856cytoskeleton IEA--

    MAP2K6 for ontologies           About GeneDecksing



    MAP2K6 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of MAP2K6
    R&D Systems Antibodies for MAP2K6 (MKK6)
    Cell Signaling Technology (CST) Antibodies for MAP2K6  (MKK6)
    OriGene Antibodies for MAP2K6
    OriGene Custom Antibody Services for MAP2K6
    GenScript Custom Superior Antibodies Services for MAP2K6
    Novus Biologicals MAP2K6 Antibodies
    Abcam antibodies for MAP2K6
    Cloud-Clone Corp. Antibodies for MAP2K6 
    ThermoFisher Antibody for MAP2K6
    LSBio Antibodies in human, mouse, rat for MAP2K6 

    Assay Products for MAP2K6: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for MAP2K6
    R&D Systems ELISAs for MAP2K6 (MKK6)         (see all)
    GenScript MAP2K6-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for MAP2K6 
    Cloud-Clone Corp. CLIAs for MAP2K6


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    MAP2K: Mitogen-activated protein kinase cascade / Kinase kinases

    IUPHAR Guide to PHARMACOLOGY protein family classification: mitogen-activated protein kinase kinase 6 
    STE7 family

    5 InterPro protein domains:
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_cat_dom

    Graphical View of Domain Structure for InterPro Entry P52564

    ProtoNet protein and cluster: P52564

    UniProtKB/Swiss-Prot: MP2K6_HUMAN, P52564
    Domain: 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
    Domain: The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK
    substrates (By similarity)
    Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase
    subfamily
    Similarity: Contains 1 protein kinase domain


    MAP2K6 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MP2K6_HUMAN, P52564
    Function: 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
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: 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
    Induction: Strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, NGF or EGF

         Genatlas biochemistry entry for MAP2K6:
    mitogen-activated protein kinase kinase 6,activated by TNFA,involved in TNFA mediated endothelial SCYA2 (MCP1)
    expression,activating PRKMK8 and p38 kinase (MAPK) and required for ABL1 induced apoptosis

         Enzyme Number (IUBMB): EC 2.7.12.21 2

         Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004708MAP kinase kinase activity TAS10848581
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding IPI15229216
         
    MAP2K6 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for MAP2K6:
     Decreased substrate adherent c  Decreased viability with cispl 

         3 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Map2k6):
     cellular  hematopoietic system  immune system 

    MAP2K6 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for MAP2K6: Map2k6tm1Ina Map2k6tm1Flv

       inGenious Targeting Laboratory - Custom generated mouse model solutions for MAP2K6 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for MAP2K6

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for MAP2K6 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for MAP2K6 

    miRNA
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MAP2K6
    5 QIAGEN miScript miRNA Assays for microRNAs that regulate MAP2K6:
    hsa-miR-374b hsa-miR-29c hsa-miR-29a hsa-miR-374a hsa-miR-29b
    SwitchGear 3'UTR luciferase reporter plasmidMAP2K6 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for MAP2K6
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MAP2K6

    Gene Editing
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    Sirion Biotech Customized adenovirus for overexpression of MAP2K6

    Clone
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    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for MAP2K6 (see all 7)
    OriGene ORF clones in mouse, rat for MAP2K6
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: MAP2K6 (NM_002758)
    Sino Biological Human cDNA Clone for MAP2K6
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MAP2K6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MAP2K6
    Sirion Biotech Customized lentivirus for stable overexpression of MAP2K6 
                         Customized lentivirus expression plasmids for stable overexpression of MAP2K6 

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K6


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for MAP2K6 About   (see all 92)                                                                                              See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Development FGF-family signaling
    Development FGF-family signaling0.63
    Development Flt3 signaling0.45
    Development FGFR signaling pathway0.50
    FGF Pathway0.38
    2BAFF in B-Cell Signaling
    BAFF in B-Cell Signaling0.92
    RANKL/RANK Signaling Pathway0.31
    APRIL Pathway0.92
    3Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway0.93
    Toll-like receptor signaling pathway0.93
    4MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    5Immune response Fc epsilon RI pathway
    Immune response Fc epsilon RI pathway0.45
    Fc epsilon RI signaling pathway0.40

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5/16 EMD Millipore Pathways for MAP2K6 (see all 16)
        G-protein signaling Regulation of p38 and JNK signaling mediated by G-proteins
    Development A2A receptor signaling
    Development Beta-adrenergic receptors signaling via cAMP
    Development TGF-beta receptor signaling
    Immune response Fc epsilon RI pathway

    4 R&D Systems Pathways for MAP2K6
        NOD-like Receptor Signaling Pathways
    Inflammasome Activation Pathways
    Toll-Like receptor Signaling Pathways
    TGF-beta Signaling Pathways

    5/79 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for MAP2K6 (see all 79)
        Toll-Like Receptors Pathway
    Molecular Mechanisms of Cancer
    eIF2 Pathway
    PACAP Signaling
    Rho Family GTPases

    1 Cell Signaling Technology (CST) Pathway for MAP2K6
        MAP Kinase Signaling

    5/19 GeneGo (Thomson Reuters) Pathways for MAP2K6 (see all 19)
        Development A2A receptor signaling
    Development FGF-family signaling
    Development Endothelin-1/EDNRA signaling
    G-protein signaling Regulation of p38 and JNK signaling mediated by G-proteins
    Transcription PPAR Pathway

    5/27 BioSystems Pathways for MAP2K6 (see all 27)
        MAPK signaling pathway
    Focal Adhesion
    MicroRNAs in cardiomyocyte hypertrophy
    Insulin Signaling
    Integrin-mediated cell adhesion

    3 Sino Biological Pathways for MAP2K6 
        Non-Canonical Wnt Pathway
    VEGF Signaling
    TGF-beta Signaling Pathway

    5/30        Reactome Pathways for MAP2K6 (see all 30)
        Developmental Biology
    Toll Like Receptor 2 (TLR2) Cascade
    Toll Like Receptor TLR6:TLR2 Cascade
    Toll-Like Receptors Cascades
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways

    2 PharmGKB Pathways for MAP2K6
        Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
    VEGF Signaling Pathway

    5/10         Kegg Pathways  (Kegg details for MAP2K6) (see all 10):
        MAPK signaling pathway
    Osteoclast differentiation
    Toll-like receptor signaling pathway
    Fc epsilon RI signaling pathway
    TNF signaling pathway


    MAP2K6 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for MAP2K6

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/76 Interacting proteins for MAP2K6 (P525641, 2, 3 ENSP000003519974) via UniProtKB, MINT, STRING, and/or I2D (see all 76)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MAPK14Q165392, 3, ENSP000002297944MINT-4300277 I2D: score=5 STRING: ENSP00000229794
    MAP3K4Q9Y6R43, ENSP000003759864I2D: score=6 STRING: ENSP00000375986
    MAP3K7O433183, ENSP000003583354I2D: score=5 STRING: ENSP00000358335
    MAP3K5Q996833, ENSP000003519084I2D: score=4 STRING: ENSP00000351908
    DCTN1Q142033, ENSP000003547914I2D: score=3 STRING: ENSP00000354791
    About this table

    Gene Ontology (GO): 5/30 biological process terms (GO ID links to tree view) (see all 30):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade ----
    GO:0000187activation of MAPK activity TAS--
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--
    GO:0002756MyD88-independent toll-like receptor signaling pathway TAS--

    MAP2K6 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    MAP2K6 for compounds           About GeneDecksing

    EMD Millipore small molecules for MAP2K6:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for MAP2K6 (MP2K6)

    2 HMDB Compounds for MAP2K6    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    10 Novoseek inferred chemical compound relationships for MAP2K6 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sb 203580 84.1 11 9575191 (1), 19578154 (1), 9442025 (1), 10960075 (1) (see all 9)
    anisomycin 80.4 5 8805335 (1), 11259586 (1), 8626699 (1), 8665897 (1)
    arsenite 41.5 3 12475989 (2), 11259586 (1)
    tyrosine 32.1 4 11304531 (1), 10514514 (1), 15601262 (1), 11062067 (1)
    mannitol 30.2 2 10816593 (2)
    serine 23.8 3 10606930 (2), 15550393 (1)
    glucose 0 3 11279172 (2)
    calcium 0 1 10788511 (1)
    vegf 0 1 14656993 (1)
    cyclosporin a 0 1 9575191 (1)

    Search CenterWatch for drugs/clinical trials and news about MAP2K6 / MP2K6

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for MAP2K6 gene (2 alternative transcripts): 
    NM_002758.3  NM_031988.1  

    Unigene Cluster for MAP2K6:

    Mitogen-activated protein kinase kinase 6
    Hs.463978  [show with all ESTs]
    Unigene Representative Sequence: BX641121
    8 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000590474 ENST00000586641 ENST00000359094(uc002jii.3 uc002jij.3 uc002jik.3)
    ENST00000589295 ENST00000588110 ENST00000589647 ENST00000591445 ENST00000592348


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    Additional mRNA sequence: 

    AB451252.1 AB451376.1 AK225719.1 AK290747.1 BC012009.1 BX641121.1 D87905.1 U39064.1 
    U39065.1 U39656.1 U39657.1 U49732.1 X96757.1 

    5 DOTS entries:

    DT.455638  DT.92421218  DT.100779127  DT.86858588  DT.40123639 

    24/107 AceView cDNA sequences (see all 107):

    X96757 CR625265 BX384725 BX282069 CR624804 BC012009 CR604345 BX364501 
    BU168274 CR616398 BU741607 AA256846 AA932919 D87905 BM724329 BQ009018 
    BE619185 AI242356 CA423885 U39657 AA814082 U49732 CN480282 N40772 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K6    About this scheme

    ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13
    SP1:        -     -     -                                                                           
    SP2:                    -                                                                           
    SP3:                                                                                                


    ECgene alternative splicing isoforms for MAP2K6

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    MAP2K6 expression in normal human tissues (normalized intensities)      MAP2K6 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    MAP2K6 Expression
    About this image


    MAP2K6 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/9 selected tissues (see all 9) fully expand
     
     Brain (Nervous System)    fully expand to see all 14 entries
             Thalamus
             Olfactory Bulb   
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Telencephalon
     
     Limb (Muscoskeletal System)    fully expand to see all 2 entries
             limb/hindlimb   
     
     Spinal Cord (Nervous System)
             Ventral Horn   
     
     Colon (Gastrointestinal Tract)
             colonic mucosal (ibs)   

    See MAP2K6 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MAP2K6

    SOURCE GeneReport for Unigene cluster: Hs.463978

    UniProtKB/Swiss-Prot: MP2K6_HUMAN, P52564
    Tissue specificity: Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle,
    heart, and in lesser extent in liver or pancreas

        SABiosciences Expression via Pathway-Focused PCR Arrays including MAP2K6: 
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              MAP Kinase (MAPK) Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for MAP2K6 gene from 7/16 species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Map2k61 , 5 mitogen-activated protein kinase kinase 61, 5 91.02(n)1
    97.9(a)1
      11 (73.60 cM)5
    263991  NM_011943.21  NP_036073.11 
     1103991225 
    chicken
    (Gallus gallus)
    Aves MAP2K61 mitogen-activated protein kinase kinase 6 84.63(n)
    96.71(a)
      417445  XM_003642348.1  XP_003642396.1 
    lizard
    (Anolis carolinensis)
    Reptilia MAP2K66
    mitogen-activated protein kinase kinase 6
    94(a)
    1 ↔ 1
    2(96222779-96332552)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.7172 Xenopus laevis MAP kinase activator XMEK3 mRNA, complete more 80.88(n)    AF172848.1 
    zebrafish
    (Danio rerio)
    Actinopterygii map2k32 mitogen-activated protein kinase kinase 3 77.91(n)   65239  AB030899.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta lic3 activation of MAPK protein kinase 60(a)   11D10   --
    worm
    (Caenorhabditis elegans)
    Secernentea sek-11 , 3 SER/THR-protein kinase3
    Protein SEK-11
    52(a)
    (best of 4)3
    56.28(n)1
    52.47(a)1
      X(7852049-7854578)3
    1810431  NM_076921.31  NP_509322.21 


    ENSEMBL Gene Tree for MAP2K6 (if available)
    TreeFam Gene Tree for MAP2K6 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for MAP2K6 gene
    MAP2K32  MAP2K52  MAP2K22  MAP2K42  MAP2K72  MAP2K12  
    18/22 SIMAP similar genes for MAP2K6 using alignment to 5 protein entries:     MP2K6_HUMAN (see all proteins) (see all similar genes):
    DKFZp686N0154    MAP2K3    MAP2K4    MAP2K7    CDK1    MAP2K5
    STK10    STK3    MYO3B    SLK    STK4    TNIK
    NEK7    MAP2K1    MAP2K2    MAP4K4    DKFZp686L02273    MINK1

    MAP2K6 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2653 SNPs in MAP2K6 are shown (see all 2653)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs107137161,2
    C,F--62798442(+) TGAAGT/-TTTTC 1 -- int1 trp32Minor allele frequency- -:0.50NA CSA 4
    rs342164511,2
    C--62802504(+) TTTTTT/-CTTCA 1 -- int11Minor allele frequency- -:0.00CSA 2
    rs2020398051,2
    C--62808566(+) GATTT-/AAAAAA 1 -- int10--------
    rs585672941,2
    C--62810632(+) TTTTT-/GTTTTT 1 -- int10--------
    rs670525381,2
    C--62810632(+) TTTTTT/GTTTTT 1 -- int13Minor allele frequency- G:0.00WA CSA 4
    rs2014896521,2
    C--62817847(+) AAAAT-/AAAAAAA 1 -- int10--------
    rs801866431,2
    --62817859(+) AAAAAC/AACAAA 1 -- int11Minor allele frequency- A:0.50NA 2
    rs676212941,2
    C--62836916(+) TTATT-/ATTTTT 1 -- int10--------
    rs676212961,2
    C,F--62836916(+) TTATTT/ATTTTT 1 -- int12Minor allele frequency- A:0.50NA 4
    rs347776821,2
    C--62836918(+) TATTA-/TTTTTT 1 -- int10--------

    HapMap Linkage Disequilibrium report for MAP2K6 (67410838 - 67539472 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for MAP2K6:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2716154CNV Deletion23290073
    nsv2130CNV Insertion18451855
    nsv520649CNV Loss19592680

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 601254    OMIM disorders: --

    20/28 diseases for MAP2K6 (see all 28):    About MalaCards
    pierre robin sequence    toxoplasmosis    cytomegalovirus infection    prostate cancer, progression of
    amyotrophic lateral sclerosis    lateral sclerosis    prostate cancer    chronic myeloid leukemia
    insulin resistance    huntington's disease    rheumatoid arthritis    alzheimer's disease
    influenza    arthritis    myocardial infarction    prostatitis
    glioblastoma    ischemia    myeloid leukemia    endotheliitis


    MAP2K6 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/13 Novoseek inferred disease relationships for MAP2K6 gene (see all 13)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 30.9 2 10606930 (1), 8861944 (1)
    shock 28 6 17490625 (1), 9029150 (1), 10514514 (1), 8626699 (1) (see all 6)
    anthrax 16.8 1 14592973 (1)
    tumors 13.4 4 17577251 (2), 12784337 (1)
    neurofibrillary tangles 12.1 2 15626821 (1)
    rheumatoid arthritis 1.08 1 15778394 (1)
    insulin resistance 0 1 12554784 (1)
    breast cancer 0 1 12475989 (1)
    osteoarthritis 0 1 14695331 (1)
    adenocarcinoma 0 1 17577251 (1)

    Genetic Association Database (GAD): MAP2K6
    Human Genome Epidemiology (HuGE) Navigator: MAP2K6 (6 documents)

    Export disorders for MAP2K6 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for MAP2K6 gene, integrated from 9 sources (see all 237):
    (articles sorted by number of sources associating them with MAP2K6)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Characterization of the structure and function of a novel MAP kinase kinase (MKK6). (PubMed id 8621675)1, 2, 3, 9 Han J.... Ulevitch R.J. (1996)
    2. Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation. (PubMed id 20364819)1, 2, 9 Sturchler E....Duckett D. (2010)
    3. Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase. (PubMed id 15550393)1, 2, 9 Kaur R....Lu M.L. (2005)
    4. Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells. (PubMed id 8861944)1, 2, 9 Cuenda A....Nebreda A.R. (1996)
    5. Cloning and characterization of MEK6, a novel member of the mitogen- activated protein kinase kinase cascade. (PubMed id 8626699)1, 2, 9 Stein B.... Barbosa M.S. (1996)
    6. Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation. (PubMed id 15229216)1, 2, 9 Silva A.M....Williams B.R. (2004)
    7. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. (PubMed id 8663074)1, 2, 9 Moriguchi T....Hagiwara M. (1996)
    8. The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription. (PubMed id 11727828)1, 2, 9 Bode J.G....Haussinger D. (2001)
    9. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. (PubMed id 11460167)1, 2, 9 Wang C.... Chen Z.J. (2001)
    10. MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. (PubMed id 8622669)1, 2, 9 Raingeaud J.... Davis R.J. (1996)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 5608 HGNC: 6846 AceView: MAP2K6 Ensembl:ENSG00000108984 euGenes: HUgn5608
    ECgene: MAP2K6 Kegg: 5608 H-InvDB: MAP2K6

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for MAP2K6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MAP2K6 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for MAP2K6 gene:
    Search GeneIP for patents involving MAP2K6

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    About This Section

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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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