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MAP2K6 Gene

protein-coding   GIFtS: 70
GCID: GC17P067410

Mitogen-Activated Protein Kinase Kinase 6


(Previous symbol: PRKMK6)
  See MAP2K6-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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. 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NT_010783.16  NC_018928.2  
Regulatory elements:
   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 Chromatin IP Primers for MAP2K6

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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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
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: 

  • 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/TAOK21
  • Acetylation of Ser-207 and Thr-211 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the
    MAPK signaling pathway1
  • Ubiquitination2 at Lys172
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for MAP2K6 (P52564) (see all 9)
     WICMELM  AILRFPY  TPPRDLDSKA  FYGALFREGD 


    See MAP2K6 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002749.2  
    ENSEMBL proteins: 
     ENSP00000468348   ENSP00000351997   ENSP00000466143   ENSP00000464916   ENSP00000467213  
    Reactome Protein details: P52564

    MAP2K6 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant MAP2K6 Protein
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    Browse recombinant and purified proteins available from Enzo Life Sciences
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    OriGene Protein Over-expression Lysate for MAP2K6
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    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

     
    Search eBioscience for Proteins for MAP2K6 

     
    antibodies-online proteins for MAP2K6 (8 products) 

     
    antibodies-online peptides for MAP2K6

    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
    Novus Biologicals MAP2K6 Antibodies
    Abcam antibodies for MAP2K6
    Cloud-Clone Corp. Antibodies for MAP2K6
    ThermoFisher Antibody for MAP2K6
    antibodies-online antibodies for MAP2K6 (160 products) 

    MAP2K6 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    R&D Systems ELISAs for MAP2K6 (MKK6)         (see all)
    GenScript Custom Assay Services for MAP2K6
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for MAP2K6
    Cloud-Clone Corp. CLIAs for MAP2K6
    Search eBioscience for ELISAs for MAP2K6 
    antibodies-online kits for MAP2K6 (15 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    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_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


    Find genes that share domains with MAP2K6           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    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): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004702receptor signaling protein serine/threonine kinase activity IBA--
    GO:0004708MAP kinase kinase activity IBA--
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding IPI15229216
         
    Find genes that share ontologies with MAP2K6           About GenesLikeMe


    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 

    Find genes that share phenotypes with MAP2K6           About GenesLikeMe

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

       genOway: Develop your customized and physiologically relevant rodent model for MAP2K6

    miRNA
    Products:
        
    miRTarBase miRNAs that target MAP2K6:
    hsa-mir-425-5p (MIRT016670), hsa-mir-145-5p (MIRT021513)

    Block miRNA regulation of human, mouse, rat MAP2K6 using miScript Target Protectors
    5 qRT-PCR 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:
        
    OriGene RNAi products in human, mouse, rat for MAP2K6
    Predesigned siRNA for gene silencing in human, mouse, rat MAP2K6

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for MAP2K6

    Clone
    Products:
         
    OriGene clones in human, mouse for MAP2K6 (see all 6)
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    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
    Addgene plasmids for MAP2K6 

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    Browse ESI BIO Cell Lines and PureStem Progenitors for MAP2K6 
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    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K6


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MP2K6_HUMAN, P52564: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Note=Binds to microtubules
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    nucleus5
    cytosol4

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IBA--
    GO:0005829cytosol TAS--
    GO:0005856cytoskeleton IEA--

    Find genes that share ontologies with MAP2K6           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for MAP2K6 About   (see all 91)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1NOD-like Receptor Signaling Pathways
    Toll-Like receptor Signaling Pathways0.58
    IL-1 Family Signaling Pathways0.44
    NOD-like Receptor Signaling Pathways0.58
    Mucin expression in CF via TLRs, EGFR signaling pathways0.42
    Inflammasome Activation Pathways0.51
    Immune response IL 1 signaling pathway0.42
    2Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway0.94
    Regulation of toll-like receptor signaling pathway0.93
    Toll-like receptor signaling pathway0.94
    3MAPK targets/ Nuclear events mediated by MAP kinases
    MAP kinase activation in TLR cascade0.61
    activated TAK1 mediates p38 MAPK activation0.00
    MAP Kinase Signaling0.31
    4Development Endothelin 1 EDNRA signaling
    Development Endothelin 1 EDNRA signaling0.41
    Inflammatory mediator regulation of TRP channels0.37
    GnRH signaling pathway0.38
    5RANK Signaling in Osteoclasts
    BAFF in B-Cell Signaling0.92
    RANKL/RANK Signaling Pathway0.31
    APRIL Pathway0.92


    Find genes that share SuperPaths with MAP2K6           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5 R&D Systems Pathways for MAP2K6
        NOD-like Receptor Signaling Pathways
    Inflammasome Activation Pathways
    IL-1 Family Signaling Pathways
    Toll-Like receptor Signaling Pathways
    TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe 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

    Selected 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

    Selected BioSystems Pathways for MAP2K6 (see all 30)
        MAPK signaling pathway
    MicroRNAs in cardiomyocyte hypertrophy
    Focal Adhesion
    Integrin-mediated cell adhesion
    Insulin Signaling

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

    5 Reactome Pathways for MAP2K6
        Interleukin-1 signaling
    Oxidative Stress Induced Senescence
    activated TAK1 mediates p38 MAPK activation
    NOD1/2 Signaling Pathway
    CDO in myogenesis

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

    Selected Kegg Pathways  (Kegg details for MAP2K6) (see all 12):
        MAPK signaling pathway
    Rap1 signaling pathway
    Osteoclast differentiation
    Toll-like receptor signaling pathway
    Fc epsilon RI signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP2K6: 
              NFKB Signaling Targets in human mouse rat
              Cellular Senescence in human mouse rat
              MAP Kinase (MAPK) Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MAP2K6

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

    Selected Interacting proteins for MAP2K6 (P525641, 2, 3 ENSP000003519974) via UniProtKB, MINT, STRING, and/or I2D (see all 132)
    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): Selected biological process terms (see all 33):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade ----
    GO:0000187activation of MAPK activity TAS--
    GO:0001934positive regulation of protein phosphorylation ----
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--

    Find genes that share ontologies with MAP2K6           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    Selected ApexBio Compounds for MAP2K6 (see all 19)     About this table
    CompoundAction CAS #
    AZD6244 (Selumetinib)Potent, selective, and ATP-uncompetitive MEK inhibitor--
    AZD8330orally active, selective MEK inhibitor[869357-68-6]
    BIX 02188MEK5-selective inhibitor[1094614-84-2]
    BIX 02189blocks MEK5 and ERK5 catalytic activity[1094614-85-3]
    Cobimetinibselective inhibitor of MEK[934660-93-2]
    MEK inhibitorPotent MEK inhibitor, Antitumor agent[334951-92-7]
    MEK162 (ARRY-162, ARRY-438162)orally available inhibitor of MEK1/2[606143-89-9]
    PD0325901MEK inhibitor[391210-10-9]
    PD184352 (CI-1040)Selective MEK inhibitor[212631-79-3]
    PD318088inhibit MEK-1 and MEK-2[391210-00-7]

    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)



    Find genes that share compounds with MAP2K6           About GenesLikeMe



    (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,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    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 

    Selected AceView cDNA sequences (see all 107):

    BX384725 AA256846 CR625265 AA932919 BM724329 AI242356 BX364501 BX282069 
    BE619185 BU741607 X96757 D87905 CR604345 BQ009018 CR616398 BU168274 
    CR624804 BC012009 BM754632 NM_031988 N40772 BI768794 U39064 CN480282 

    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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MAP2K6 expression in normal human tissues (normalized intensities)
    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
     selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Midbrain tegmentum
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Ovary (Reproductive System)
             Oviduct
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
    MAP2K6 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MAP2K6 Protein Expression

    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

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP2K6: 
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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)
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    This gene was present in the common ancestor of animals.

    Orthologs for MAP2K6 gene from Selected 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_003642348.2  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
    sek-11
    52(a)
    (best of 4)3
    56.28(n)1
    52.47(a)1
      X(7852049-7854578)3
    1810431  NM_076921.41  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)
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    Paralogs for MAP2K6 gene
    MAP2K32  MAP2K52  MAP2K22  MAP2K42  MAP2K72  MAP2K12  
    Selected 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

    Find genes that share paralogs with MAP2K6           About GenesLikeMe



    (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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MAP2K6 (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

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 601254    OMIM disorders: --

    1 disease for MAP2K6:    
    About MalaCards
    pierre robin sequence


    Find genes that share disorders with MAP2K6           About GenesLikeMe

    Selected 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)
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    PubMed articles for MAP2K6 gene, integrated from 10 sources (see all 238):
    (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. (J. Biol. Chem. 1996)
    2. Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation. (PubMed id 20364819)1, 2, 9 Sturchler E.... Duckett D. (Biochemistry 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. (J. Biol. Chem. 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. (EMBO J. 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. (J. Biol. Chem. 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. (J. Biol. Chem. 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. (J. Biol. Chem. 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. (Biol. Chem. 2001)
    9. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. (PubMed id 11460167)1, 2, 9 Wang C.... Chen Z.J. (Nature 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. (Mol. Cell. Biol. 1996)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     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)
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    Entrez Gene: 5608 HGNC: 6846 AceView: MAP2K6 Ensembl:ENSG00000108984 euGenes: HUgn5608
    ECgene: MAP2K6 Kegg: 5608 H-InvDB: MAP2K6

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    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.)
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    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



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