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

MAP2K6 Gene

protein-coding   GIFtS: 67
GCID: GC17P067410

mitogen-activated protein kinase kinase 6


(Previous symbol: PRKMK6)
 Explore 32 diseases affiliated with
MAP2K6 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for MAP2K6    

Aliases
for MAP2K6 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Mitogen-Activated Protein Kinase Kinase 61 2     MAPKK 62 3
MEK61 2 3 5     MEK 62 3
MKK61 2 3 5     SAPK Kinase 32 3
PRKMK61 2 3 5     EC 2.7.12.23 8
SAPKK31 2 3     Dual Specificity Mitogen-Activated Protein Kinase Kinase 62
MAPKK61 2 5     Protein Kinase, Mitogen-Activated, Kinase 6 (MAP Kinase Kinase 6)2
Stress-Activated Protein Kinase Kinase 32 3     SKK33
SAPKK-32 3     MAP Kinase Kinase 63
MAPK/ERK Kinase 62 3     

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


Summaries
for MAP2K6 gene

(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:
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)

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NC_018928.1  NT_010783.15  
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

Proteins
for MAP2K6 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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
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

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
  • View modification sites using PhosphoSitePlus2
  • 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 MOPED and PaxDb:    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
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein: MAP2K6
    OriGene Protein Over-expression Lysate: MAP2K6
    OriGene Custom Protein Services for MAP2K6 
    GenScript Custom Purified and Recombinant Proteins Services for MAP2K6
    Novus Biologicals MAP2K6 Proteins
    Novus Biologicals MAP2K6 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn 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 (see all 3): MAP2K6
    OriGene Custom Antibody Services for MAP2K6 
    GenScript Custom Superior Antibodies Services for MAP2K6
    Novus Biologicals MAP2K6 Antibodies
    Abcam antibodies for MAP2K6 
    Uscn Antibodies for MAP2K6
    ThermoFisher Antibody for MAP2K6

    Assay Products for MAP2K6: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    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
    Uscn ELISAs and CLIAs for MAP2K6

    Protein Domains /
    Families
    for MAP2K6 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    MAP2K6 for domains           About GeneDecksing

    5 InterPro domains/families:
     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


    Function
    for MAP2K6 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, 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, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 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): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004708MAP kinase kinase activity TAS10848581
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding ----
    GO:0005524ATP binding IEA--
         
    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:
         Mouse knock-outs for MAP2K6: Map2k6tm1Ina Map2k6tm1Flv
       inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for MAP2K6 

    miRNA
    Products:            		 OriGene 3'-UTR Clone: MAP2K6
    Browse MicroRNA Expression Plasmids
    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 plasmid: MAP2K6 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MAP2K6 (see all 7)
    OriGene shRNA RFP: MAP2K6
    OriGene siRNA: MAP2K6
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MAP2K6
    Sirion Biotech Custom design and validation of potent shRNA sequences against MAP2K6 

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for MAP2K6
    Sirion Biotech Customized adenovirus for overexpression of MAP2K6 
    Sirion Biotech Customized adenovirus for potent knockdown of MAP2K6

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MAP2K6 (see all 3)
    OriGene untagged cDNA clones in CMV expression vector in human, 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 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for MAP2K6
    Search LifeMap BioReagents cell lines for MAP2K6
    Sirion Biotech Customized stable knockdown cell line services for MAP2K6 
    Sirion Biotech Customized inducible knockdown cell line services for MAP2K6
    Sirion Biotech Customized stable overexpressing cell line services for MAP2K6
    Sirion Biotech Customized inducible overexpressing cell line services for MAP2K6

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K6


    Pathways & Interactions
    for MAP2K6 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/91 super-pathways (see all 91) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1TRAF6 Mediated Induction of proinflammatory cytokines
    8/19 pathways (see all 19)
    		TRAF6 Mediated Induction of proinflammatory cytokines1.00
    		Toll Like Receptor TLR1:TLR2 Cascade0.78
    		MAP kinase activation in TLR cascade0.88
    		Toll Like Receptor 2 (TLR2) Cascade0.78
    		Toll Like Receptor 5 (TLR5) Cascade0.86
    		MyD88:Mal cascade initiated on plasma membrane0.78
    		Toll Like Receptor 10 (TLR10) Cascade0.86
    		TRIF-mediated TLR3/TLR4 signaling 0.73
    2ErbB4 Pathway
    8/12 pathways (see all 12)
    		ErbB4 Pathway1.00
    		LPS Stimulated MAPK Signaling0.36
    		ErbB Family Pathway0.59
    		VEGF Signaling Pathway0.35
    		Prolactin Signaling0.54
    		TREM1 Pathway0.32
    		ErbB2-ErbB3 Heterodimers0.47
    		HMGB1 Pathway0.32
    34-1BB Pathway
    		4-1BB Pathway1.00
    		PKR Pathway0.36
    		CD40 Signaling0.54
    		NF-KappaB Activation by EBV0.31
    		CD27 Pathway0.48
    		SUMO Pathway0.30
    		CMV and MAPK Pathways0.38
    4CNTF Signaling
    		CNTF Signaling1.00
    		OSM Pathway0.46
    		FLT3 Signaling0.50
    		Nur77-Induced AICD in Macrophage0.27
    		IL-3 Pathway0.46
    5Development FGFR signaling pathway
    		Development FGFR signaling pathway1.00
    		Development_Flt3 signaling0.45
    		Development_FGFR signaling pathway0.98
    		Development Flt3 signaling0.45

    Pathway sources
    See GeneCards unified pathways
    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

    3 R&D Systems Pathways for MAP2K6
        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) 
        Integrin-mediated cell adhesion
    Focal Adhesion
    MAPK signaling pathway
    MicroRNAs in cardiomyocyte hypertrophy
    p38 MAPK Signaling Pathway

    5/31        Reactome Pathways for MAP2K6 (see all 31)
        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

    5/8         Kegg Pathways  (Kegg details for MAP2K6) (see all 8):
        MAPK signaling pathway
    Osteoclast differentiation
    Toll-like receptor signaling pathway
    Fc epsilon RI signaling pathway
    GnRH 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)

    5/75 Interacting proteins for MAP2K6 (P525642, 3 ENSP000003519974) via UniProtKB, MINT, STRING, and/or I2D (see all 75)
    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): 5/27 biological process terms (GO ID links to tree view) (see all 27):    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



    Drugs & Compounds
    for MAP2K6 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, 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

    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 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 

    Transcripts
    for MAP2K6 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, 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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    Inhib. RNA
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    Additional cDNA 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):

    D87905 CR625265 AA932919 AA256846 BM724329 AI242356 BX364501 BX282069 
    CR604345 BX384725 BE619185 CR616398 BU168274 CR624804 BC012009 BQ009018 
    BU741607 X96757 BX333105 CA423885 BU741058 AI499433 BM754632 NM_031988 

    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

    Expression
    for MAP2K6 gene

    (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)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --
    MAP2K6 Expression
    About this image

    MAP2K6 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table

    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    ES04(HES-4) (Embryonic Stem Cell)Early Embryo, Inner Cell Mass
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    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
    for MAP2K6 gene

    (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 eukaryotes.

    Orthologs for MAP2K6 gene from 8/28 species (see all 28)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    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
    		 --
    		 92(a)
    		 1 ↔ 1
    		 2(96284597-96312039)
    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 
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons ATMKK96
    ATMKK66
    (see all 10)    		 mitogen-activated protein kinase kinase 6
    (see all 10)    		 29(a)
    28(a)
    (see all 10)    		 possible ortholog
    possible ortholog
    (see all 10)    		 1(27639091-27640529)
    5(22904689-22906661)
    rice
    (Oryza sativa)    		 Liliopsida --
    --
    (see all 11)    		 OsMKK1 - putative MAPKK based on amino acid sequen...
    STE_MEK_ste7_MAP2K.2 - STE kinases include homolog...
    (see all 11)    		 29(a)
    28(a)
    (see all 11)    		 possible ortholog
    possible ortholog
    (see all 11)    		 6(2497848-2501902)
    1(17903729-17909128)


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

    Paralogs
    for MAP2K6 gene

    (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    MAP2K5    STK10
    STK3    MYO3B    SLK    STK4    TNIK    NEK7
    MAP2K1    MAP2K2    MAP4K4    DKFZp686L02273    MINK1    MST4

    MAP2K6 for paralogs           About GeneDecksing



    Genomic Variants
    for MAP2K6 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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

    10/2202 NCBI SNPs in MAP2K6 are shown (see all 2202)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 17 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs126034371,2
    		C,H--62794711(+) TTCCAG/ACATCC 1 -- us2k14Minor allele frequency- A:0.00NS EA 418
    rs617580321,2
    		C--62795161(+) CTCCAT/AGAAGT 1 -- us2k13Minor allele frequency- A:0.01NS NA 208
    rs80810271,2
    		C,F--62795358(+) GCACAT/GCCTGG 1 -- us2k13Minor allele frequency- G:0.03NS WA 204
    rs25922101,2
    		C,F,H--62795510(+) TTAGCG/ATTGAT 1 -- us2k17Minor allele frequency- A:0.00NS EA NA 710
    rs617580351,2
    		C,F--62795860(+) ACCCCG/ATCTCT 1 -- us2k14Minor allele frequency- A:0.06NS WA 192
    rs617580361,2
    		C,F--62796177(+) AAGCCA/GAAAGC 1 -- us2k12Minor allele frequency- G:0.05NS 94
    rs617580371,2
    		F--62796930(+) CACAGAGAG/-  
                TTCCT     		1 -- int12Minor allele frequency- -:0.03NS 94
    rs601628001,2
    		F--62797816(+) TTTCTT/CTACCA 1 -- int11Minor allele frequency- C:0.06WA 118
    rs116523411,2
    		H--62798092(+) TATTAG/TGGGAG 1 -- int14Minor allele frequency- T:0.00NS EA 418
    rs1115520691,2
    		--62798233(+) TCCATG/ACTTTG 1 -- int11Minor allele frequency- A:0.50CSA 2

    HapMap Linkage Disequilibrium report for MAP2K6 (67410838 - 67539472 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for MAP2K6: --

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    Disorders / Diseases
    for MAP2K6 gene

    (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.)
    About This Section
    MAP2K6 for disorders           About GeneDecksing

    OMIM gene information: 601254    OMIM disorders: --

    20/32 diseases for MAP2K6 (see all 32):    About MalaCards
    pierre robin sequence    amyotrophic lateral sclerosis (als)    amyotrophic lateral sclerosis    lateral sclerosis
    insulin resistance    cytomegalovirus infection    rheumatoid arthritis    chronic myeloid leukemia
    myeloid leukemia    myocardial infarction    prostate cancer    alzheimer's disease
    prostate cancer, progression of    osteoarthritis    huntington's disease    toxoplasmosis
    arthritis    breast cancer    hepatocellular carcinoma    ovarian carcinoma

    10/13 Novoseek 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)

    Human Genome Epidemiology (HuGE) Navigator: MAP2K6 (6 documents)

    Export disorders for MAP2K6 gene to outside databases

    Publications
    for MAP2K6 gene

    (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 230):
    (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. 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)
    7. 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)
    8. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. (PubMed id 11460167)1, 2, 9 Wang C.... Chen Z.J. (2001)
    9. 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)
    10. MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases. (PubMed id 20869211)1, 2 Kim M.Y....Yoon T.J. (2010)

    External Searches for MAP2K6 gene

    (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)

    Genome Databases showing MAP2K6 gene

    (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

    Other Databases showing MAP2K6 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing MAP2K6 gene

    (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

    Intellectual Property
    for MAP2K6 gene

    (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



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    About This Section

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