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MAP2K4 Gene

protein-coding   GIFtS: 71
GCID: GC17P011864

Mitogen-Activated Protein Kinase Kinase 4


(Previous symbol: SERK1)
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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)
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Aliases
Mitogen-Activated Protein Kinase Kinase 41 2     C-Jun N-Terminal Kinase Kinase 12 3
SERK11 2 3 5     JNK-Activating Kinase 12 3
JNKK12 3 5     MAP Kinase Kinase 42 3
PRKMK42 3 5     MAPK/ERK Kinase 42 3
Stress-Activated Protein Kinase Kinase 12 3     MAPKK 42 3
JNKK2 3     MEK 42 3
MEK42 3     SAPK/ERK Kinase 12 3
MKK42 3     EC 2.7.12.23 8
SAPKK-12 3     MAPKK42 5
SAPKK12 3     Dual Specificity Mitogen-Activated Protein Kinase Kinase 42
SEK12 3     JNK-Activated Kinase 12
SKK12 3     SAPK Kinase 13

External Ids:    HGNC: 68441   Entrez Gene: 64162   Ensembl: ENSG000000655597   OMIM: 6013355   UniProtKB: P459853   

Export aliases for MAP2K4 gene to outside databases

Previous GC identifers: GC17P012290 GC17P013039 GC17P011868 GC17P012124


(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 MAP2K4 Gene:
This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an
integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such
as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling
module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by
MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar
protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on
the long arm of chromosome X. Alternative splicing results in multiple transcript variants. (provided by RefSeq,
Jul 2013)

GeneCards Summary for MAP2K4 Gene:
MAP2K4 (mitogen-activated protein kinase kinase 4) is a protein-coding gene. Diseases associated with MAP2K4 include hypertrophic scars, and pancreatic endocrine tumors. 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: MP2K4_HUMAN, P45985
Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal
transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase
(SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the
stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and
MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the
phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and
MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the
prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate
both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining
peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling
pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates
JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14

Gene Wiki entry for MAP2K4 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:
NC_000017.11  NT_010718.17  NC_018928.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the MAP2K4 gene promoter:
         GR   ER-alpha   AML1a   AP-1   ATF-2   CUTL1   NF-E2 p45   GR-alpha   c-Jun   NF-E2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMAP2K4 promoter sequence
   Search Chromatin IP Primers for MAP2K4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MAP2K4


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

Entrez Gene cytogenetic band: 17p12   Ensembl cytogenetic band:  17p12   HGNC cytogenetic band: 17p12

MAP2K4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAP2K4 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P011864:  view genomic region     (about GC identifiers)

Start:
11,924,135 bp from pter      End:
12,047,147 bp from pter
Size:
123,013 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, 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., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: MP2K4_HUMAN, P45985 (See protein sequence)
Recommended Name: Dual specificity mitogen-activated protein kinase kinase 4  
Size: 399 amino acids; 44288 Da
Subunit: Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1,
MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like
MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3
3 PDB 3D structures from and Proteopedia for MAP2K4:
3ALN (3D)        3ALO (3D)        3VUT (3D)    
Secondary accessions: B2R7N7 B3KYB2 D3DTS5 Q5U0B8 Q6FHX4 Q6P9H2 Q6PIE6
Alternative splicing: 2 isoforms:  P45985-1   P45985-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for MAP2K4: NX_P45985

Explore proteomics data for MAP2K4 at MOPED

Post-translational modifications: 

  • Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks)1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • 4 DME Specific Peptides for MAP2K4 (P45985)
     WICMELM  FYGALFREGD  IKLCDFGISG  YDVRSDVWSLGITLYE 


    See MAP2K4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001268364.1  NP_003001.1  

    ENSEMBL proteins: 
     ENSP00000262445   ENSP00000463507   ENSP00000410402   ENSP00000473582   ENSP00000473472  
     ENSP00000473606   ENSP00000473458   ENSP00000473511   ENSP00000467239  
    Reactome Protein details: P45985

    MAP2K4 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant MAP2K4 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for MAP2K4
    OriGene Protein Over-expression Lysate for MAP2K4
    OriGene MassSpec for MAP2K4
    OriGene Custom Protein Services for MAP2K4
    GenScript Custom Purified and Recombinant Proteins Services for MAP2K4
    Novus Biologicals MAP2K4 Proteins
    Novus Biologicals MAP2K4 Lysates
    Sino Biological Recombinant Protein for MAP2K4
    Sino Biological Cell Lysate for MAP2K4
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for MAP2K4

    MAP2K4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of MAP2K4
    R&D Systems Antibodies for MAP2K4 (MKK4)
    Cell Signaling Technology (CST) Antibodies for MAP2K4  (MKK4)
    OriGene Antibodies for MAP2K4
    OriGene Custom Antibody Services for MAP2K4
    Novus Biologicals MAP2K4 Antibodies
    Abcam antibodies for MAP2K4 (P45985, Q6FHX4, Q6PIE6, Q6P9H2)
    Cloud-Clone Corp. Antibodies for MAP2K4
    ThermoFisher Antibody for MAP2K4
    LSBio Antibodies in human, mouse, rat for MAP2K4

    MAP2K4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for MAP2K4
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for MAP2K4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for MAP2K4
    Cloud-Clone Corp. CLIAs for MAP2K4


    (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 4
    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 P45985

    ProtoNet protein and cluster: P45985

    UniProtKB/Swiss-Prot: MP2K4_HUMAN, P45985
    Domain: The DVD domain (residues 364-387) 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 34-52) contains a conserved docking site and is required for the binding to MAPK
    substrates
    Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase
    subfamily
    Similarity: Contains 1 protein kinase domain


    MAP2K4 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,
    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, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MP2K4_HUMAN, P45985
    Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal
    transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase
    (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the
    stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and
    MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the
    phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and
    MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the
    prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate
    both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining
    peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling
    pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates
    JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Activated in response to a variety of cellular stresses, including UV and gamma-irradiation,
    heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by
    developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1,
    MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK

         Genatlas biochemistry entry for MAP2K4:
    mitogen-activated protein kinase kinase 4,binding to JUN transactivation domain and phosphorylating it,involved in
    signal transduction,also involved in Ras pathway and hepatogenesis

         Enzyme Number (IUBMB): EC 2.7.12.21 2

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity TAS7716521
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004708MAP kinase kinase activity ----
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding IPI9808624
         
    MAP2K4 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for MAP2K4:
     Decreased substrate adherent c  Increased colony dispersion (i  Increased mitotic index 

         11 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Map2k4):
     behavior/neurological  cardiovascular system  cellular  growth/size/body  hematopoietic system 
     integument  liver/biliary system  mortality/aging  nervous system  normal 
     other 

    MAP2K4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for MAP2K4: Map2k4tm1Flv Map2k4tm1Liz Map2k4tm1Pngr

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for MAP2K4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for MAP2K4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for MAP2K4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for MAP2K4

    miRNA
    Products:
        
    miRTarBase miRNAs that target MAP2K4:
    hsa-mir-26b-5p (MIRT028937), hsa-mir-375 (MIRT019756), hsa-mir-15b-5p (MIRT023483)

    Block miRNA regulation of human, mouse, rat MAP2K4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate MAP2K4 (see all 132):
    hsa-miR-631 hsa-miR-938 hsa-miR-128 hsa-miR-3921 hsa-miR-92b hsa-miR-3690 hsa-miR-1231 hsa-miR-548y
    SwitchGear 3'UTR luciferase reporter plasmidMAP2K4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for MAP2K4
    Predesigned siRNA for gene silencing in human, mouse, rat MAP2K4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for MAP2K4

    Clone
    Products:
         
    OriGene clones in human, mouse for MAP2K4 (see all 13)
    OriGene ORF clones in mouse, rat for MAP2K4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: MAP2K4 (NM_003010)
    Sino Biological Human cDNA Clone for MAP2K4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MAP2K4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MAP2K4

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for MAP2K4
    Browse ESI BIO Cell Lines and PureStem Progenitors for MAP2K4 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K4


    (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
    MP2K4_HUMAN, P45985: Cytoplasm (By similarity). Nucleus (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus2
    mitochondrion1

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005829cytosol TAS--
    GO:0032839dendrite cytoplasm IEA--
    GO:0043204perikaryon IEA--

    MAP2K4 for ontologies           About GeneDecksing


    (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 MAP2K4 About   (see all 99)  
    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
    2Immune response Fc epsilon RI pathway
    Immune response Fc epsilon RI pathway0.43
    Fc-epsilon receptor I signaling in mast cells0.34
    Fc epsilon RI signaling pathway0.41
    3TWEAK Pathway
    TNFR1 Pathway0.56
    Apoptosis through Death Receptors0.42
    TNF Signaling0.55
    Fas Signaling0.35
    Apoptosis and survival TNFR1 signaling pathway0.52
    4Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway0.94
    Chagas disease (American trypanosomiasis)0.32
    Toll-like receptor signaling pathway0.94
    Hepatitis B0.31
    Regulation of toll-like receptor signaling pathway0.93
    5MAPK targets/ Nuclear events mediated by MAP kinases
    MAP kinase activation in TLR cascade0.61
    JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK10.00
    MAP Kinase Signaling0.31

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5 R&D Systems Pathways for MAP2K4
        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 MAP2K4 (see all 87)
        eIF2 Pathway
    JNK Pathway
    PACAP Signaling
    Rho Family GTPases
    Insulin Receptor Pathway

    1 Cell Signaling Technology (CST) Pathway for MAP2K4
        MAP Kinase Signaling

    Selected GeneGo (Thomson Reuters) Pathways for MAP2K4 (see all 30)
        Immune response MIF in innate immunity response
    Transcription P53 signaling pathway
    Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
    Development EGFR signaling pathway
    Development Endothelin-1/EDNRA signaling

    Selected BioSystems Pathways for MAP2K4 (see all 30)
        MAPK signaling pathway
    MicroRNAs in cardiomyocyte hypertrophy
    Apoptosis
    Insulin Signaling
    Wnt Signaling Pathway and Pluripotency

    4 Sino Biological Pathways for MAP2K4
        EGFR Signaling Pathway
    Non-Canonical Wnt Pathway
    VEGF Signaling
    TGF-beta Signaling Pathway

    4 Reactome Pathways for MAP2K4
        Interleukin-1 signaling
    Oxidative Stress Induced Senescence
    JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
    FCERI mediated MAPK activation

    2 PharmGKB Pathways for MAP2K4
        Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
    VEGF Signaling Pathway

    Selected Kegg Pathways  (Kegg details for MAP2K4) (see all 12):
        MAPK signaling pathway
    ErbB signaling pathway
    Toll-like receptor signaling pathway
    Fc epsilon RI signaling pathway
    TNF signaling pathway


    MAP2K4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP2K4 (see all 7): 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              TNF Ligands & Receptors in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat
              Antifungal Response in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MAP2K4

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

    Selected Interacting proteins for MAP2K4 (P459851, 2, 3 ENSP000002624454) via UniProtKB, MINT, STRING, and/or I2D (see all 696)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MAP3K1Q132331, 3, ENSP000003824234EBI-447868,EBI-49776 I2D: score=8 STRING: ENSP00000382423
    ARRB2P321212, 3, ENSP000002692604MINT-7263286 I2D: score=3 STRING: ENSP00000269260
    MAP2K7O147332, 3, ENSP000003810664MINT-7947479 I2D: score=2 STRING: ENSP00000381066
    ARRB1P494072, 3, ENSP000003771414MINT-7263269 I2D: score=1 STRING: ENSP00000377141
    CFLARO155192, 3, ENSP000003124554MINT-3391445 I2D: score=1 STRING: ENSP00000312455
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade ----
    GO:0001934positive regulation of protein phosphorylation ----
    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--

    MAP2K4 for ontologies           About GeneDecksing



    (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)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MAP2K4 (MP2K4)

    2 HMDB Compounds for MAP2K4    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--

    Selected Novoseek inferred chemical compound relationships for MAP2K4 gene (see all 36)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    anisomycin 77.7 3 9295340 (1), 16802349 (1), 17699104 (1)
    sp 600125 73.9 5 17085668 (2), 16601071 (1), 15040011 (1), 16300886 (1)
    sb 203580 61 1 11118445 (1)
    rottlerin 50.7 1 11314034 (1)
    threonine 45.2 5 20156194 (2), 11062067 (2), 9516438 (1)
    pd 98,059 40.6 2 11483663 (1), 10843986 (1)
    12-o-tetradecanoylphorbol 13-acetate 37.6 7 9858570 (2), 9733728 (1), 18234971 (1), 10807930 (1)
    tyrosine 36 15 11062067 (3), 20156194 (2), 9890951 (2), 10713072 (1) (see all 7)
    4-hydroxynonenal 33.8 6 10953046 (2), 11306108 (2), 19248828 (1), 18276794 (1)
    ly294002 30.4 2 11707464 (1), 16115952 (1)



    MAP2K4 for compounds           About GeneDecksing



    (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,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for MAP2K4 gene (2 alternative transcripts): 
    NM_001281435.1  NM_003010.3  

    Unigene Cluster for MAP2K4:

    Mitogen-activated protein kinase kinase 4
    Hs.514681  [show with all ESTs]
    Unigene Representative Sequence: AK131544
    15 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000353533(uc002gnj.3 uc010vvi.2 uc010vvj.2) ENST00000582183
    ENST00000415385(uc002gnk.3) ENST00000602811 ENST00000602375 ENST00000602305
    ENST00000602686 ENST00000602537 ENST00000538465 ENST00000582897 ENST00000581941
    ENST00000579089 ENST00000582377 ENST00000585076 ENST00000536413

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    hsa-miR-631 hsa-miR-938 hsa-miR-128 hsa-miR-3921 hsa-miR-92b hsa-miR-3690 hsa-miR-1231 hsa-miR-548y
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    OriGene ORF clones in mouse, rat for MAP2K4
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    GenScript: all cDNA clones in your preferred vector: MAP2K4 (NM_003010)
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      QuantiTect SYBR Green Assays in human, mouse, rat MAP2K4
      QuantiFast Probe-based Assays in human, mouse, rat MAP2K4

    Additional mRNA sequence: 

    AK122997.1 AK131544.1 AK294923.1 AK313053.1 AK316100.1 AK316177.1 BC036032.1 BC050386.1 
    BC060764.1 BT019676.1 CR536564.1 L31902.1 L36870.1 U17743.1 

    17 DOTS entries:

    DT.101981454  DT.91746360  DT.100781239  DT.95113864  DT.97781931  DT.121295112  DT.100781235  DT.120996705 
    DT.91746362  DT.91746373  DT.91964505  DT.100025254  DT.100781234  DT.120996710  DT.120996738  DT.120996759 
    DT.91746365 

    Selected AceView cDNA sequences (see all 191):

    BC036032 AI347169 BM461511 Z40358 BQ688042 AK122997 AA258067 AA594527 
    BP364452 R93057 CA503301 AU155387 AW148655 AA293050 BU178994 AI613302 
    AU119785 AU137540 T70269 BQ688882 BM718928 CR601866 AI147099 AA810268 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K4 (see all 6)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c
    SP1:                    -                                   -     -                                             
    SP2:        -           -                                   -     -                                             
    SP3:                                                        -     -                                             
    SP4:                                            -           -     -                 -                           
    SP5:                                                                                                            


    ECgene alternative splicing isoforms for MAP2K4

    (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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    MAP2K4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAATCGAAGT
    MAP2K4 Expression
    About this image


    MAP2K4 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
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Blood (Hematopoietic System)
             Granulocytes Peripheral Blood
     
     Peripheral Nervous System (Nervous System)
     
     Spinal Cord (Nervous System)
    MAP2K4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MAP2K4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.514681

    UniProtKB/Swiss-Prot: MP2K4_HUMAN, P45985
    Tissue specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other
    tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MAP2K4 (see all 7): 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              TNF Ligands & Receptors in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat
              Antifungal Response in human mouse rat

    Primer
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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K4

    (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 MAP2K4 gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Map2k41 , 5 mitogen-activated protein kinase kinase 41, 5 95.21(n)1
    98.4(a)1
      11 (40.53 cM)5
    263981  NM_009157.41  NP_033183.11 
     656882435 
    chicken
    (Gallus gallus)
    Aves MAP2K41 mitogen-activated protein kinase kinase 4 89.18(n)
    96.54(a)
      417312  XM_415583.4  XP_415583.4 
    lizard
    (Anolis carolinensis)
    Reptilia MAP2K46
    mitogen-activated protein kinase kinase 4
    76(a)
    1 ↔ 1
    2(108743236-108794026)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.133082 X.laevis mRNA for Xenopus MAP Kinase Activator 2 (XMEK2) 83.66(n)    Z22736.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.104512 Danio rerio mRNA for MKK4, complete cds 79.01(n)    AB030901.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Mkk41 , 3 activation of JUN kinase receptor
    signaling protein more3
    MAP kinase kinase 41
    67(a)
    (best of 2)3
    57.38(n)1
    63.79(a)1
      85A53
    410201  NM_001170080.21  NP_001163551.11 
    worm
    (Caenorhabditis elegans)
    Secernentea sek-13 SER/THR-protein kinase 51(a)
    (best of 4)
      X(7852049-7854578)   --


    ENSEMBL Gene Tree for MAP2K4 (if available)
    TreeFam Gene Tree for MAP2K4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MAP2K4 gene
    MAP2K32  MAP2K52  MAP2K22  MAP2K62  MAP2K72  MAP2K12  
    9 SIMAP similar genes for MAP2K4 using alignment to 5 protein entries:     MP2K4_HUMAN (see all proteins):
    MAP2K6    MAP2K3    MAP2K7    MAP2K5    STK3    STK4
    MAP2K1    MAP2K2    DKFZp686L02273

    MAP2K4 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for MAP2K4
    PGOHUM00000241393


    (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 MAP2K4 (see all 2328)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0408224
    A colorectal adenocarcinoma sample4--see VAR_0408222 A T mis40--------
    VAR_0408194
    A colorectal adenocarcinoma sample4--see VAR_0408192 R W mis40--------
    VAR_0408204
    An ovarian serous carcinoma sample4--see VAR_0408202 N I mis40--------
    VAR_0408184
    A lung squamous cell carcinoma sample4--see VAR_0408182 Q L mis40--------
    VAR_0408214
    A metastatic melanoma sample4--see VAR_0408212 S N mis40--------
    rs566985501,2
    C--11870244(+) TTTTT-/TAATAC 1 -- int10--------
    rs1163064291,2
    C,F--11922238(+) TTGAAG/TGTTTT 1 -- us2k12Minor allele frequency- T:0.20WA NA 238
    rs2009810671,2
    --11922245(+) TTTCC-/TATATAT 1 -- us2k10--------
    rs1489176321,2
    C--11922612(+) TTGGA-/TGTGTG
            
    TGTGT
    1 -- us2k10--------
    rs1850352171,2
    --11922678(+) AGTTGC/GCTAAT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for MAP2K4 (11924135 - 12047147 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for MAP2K4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv1983CNV Insertion18451855
    esv25918CNV Loss19812545
    dgv3060n71CNV Gain21882294
    esv991595CNV Gain20482838

    Human Gene Mutation Database (HGMD): MAP2K4
    4 Site Specific Mutation Identification with PCR Assays for MAP2K4:
    Cosmic IdAA Change
    79380p.R110*
    20411p.R154W
    26108p.S280*
    26105p.S184L
    1 Copy Number PCR Panel containing MAP2K4:
    Kinases & Phosphatases
    SeqTarget long-range PCR primers for resequencing MAP2K4
    DNA2.0 Custom Variant and Variant Library Synthesis for MAP2K4

    (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.)
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    OMIM gene information: 601335    OMIM disorders: --

    Selected diseases for MAP2K4 (see all 51):    
    About MalaCards
    hypertrophic scars    pancreatic endocrine tumors    hereditary spastic paraplegia    trypanosomiasis
    paraplegia    huntington's disease    chagas disease    cytomegalovirus infection
    laryngeal squamous cell carcinoma    gastric adenocarcinoma    glioblastoma multiforme    spasticity
    sjogren's syndrome    prostate cancer    laryngitis    pancreatitis
    pancreatic cancer    rhabdomyosarcoma    malignant glioma    ovarian cancer


    MAP2K4 for disorders           About GeneDecksing


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

    Selected Novoseek inferred disease relationships for MAP2K4 gene (see all 21)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pancreatic carcinoma 44.4 5 15623633 (2), 9331070 (1), 9622070 (1)
    metastasis 26.1 28 12650604 (3), 16489030 (3), 18337456 (2), 15623633 (2) (see all 14)
    tumors 22.4 30 9622070 (4), 11754110 (3), 17276500 (3), 17577251 (2) (see all 12)
    prostate cancer 22.3 19 11306453 (5), 17577251 (4), 18337456 (2), 19638505 (2) (see all 5)
    anthrax 20 2 15843553 (1), 12788955 (1)
    ovarian cancer 14.6 14 17276500 (3), 12438272 (3), 10075725 (1), 16489030 (1) (see all 6)
    ovarian carcinoma 13.4 3 9926932 (1), 16489030 (1)
    cancer 11.9 17 16492916 (2), 19610067 (2), 16740690 (2), 9331070 (1) (see all 10)
    shock 11.4 1 10082520 (1)
    allelic loss 9.45 4 12376211 (1), 11306453 (1)

    Genetic Association Database (GAD): MAP2K4
    Human Genome Epidemiology (HuGE) Navigator: MAP2K4 (6 documents)

    Export disorders for MAP2K4 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 MAP2K4 gene, integrated from 10 sources (see all 395):
    (articles sorted by number of sources associating them with MAP2K4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. (PubMed id 7716521)1, 2, 3 Lin A.... Karin M. (Science 1995)
    2. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. (PubMed id 9622070)1, 2, 9 Su G.H....Kern S.E. (Cancer Res. 1998)
    3. The association between -1304T&gt;G polymorphism in the promoter of MKK4 gene and the risk of sporadic colorectal cancer in southern Chinese population. (PubMed id 19610067)1, 4, 9 Wei Y....Wang J. (Int. J. Cancer 2009)
    4. A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates. (PubMed id 12788955)1, 2, 9 Ho D.T.... Bardwell L. (J. Biol. Chem. 2003)
    5. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. (PubMed id 7839144)1, 2, 9 Derijard B.... Davis R.J. (Science 1995)
    6. The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. (PubMed id 21333379)1, 2 Haeusgen W.... Waetzig V. (Eur. J. Cell Biol. 2011)
    7. Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state. (PubMed id 20732303)1, 2 Matsumoto T.... Tada T. (Biochem. Biophys. Res. Commun. 2010)
    8. A functional variant (-1304T&gt;G) in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity. (PubMed id 20554746)1, 4 Liu B....Lu J. (Carcinogenesis 2010)
    9. Diverse physiological functions of MKK4 and MKK7 during early embryogenesis. (PubMed id 20801953)1, 2 Asaoka Y. and Nishina H. (J. Biochem. 2010)
    10. Genetic mutations associated with cigarette smoking in pancreatic cancer. (PubMed id 19351817)1, 4 Blackford A....Hruban R.H. (Cancer Res. 2009)

    (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: 6416 HGNC: 6844 AceView: MAP2K4 Ensembl:ENSG00000065559 euGenes: HUgn6416
    ECgene: MAP2K4 Kegg: 6416 H-InvDB: MAP2K4

    (According to HUGE)
    About This Section

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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)
    About This Section

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    NameDescription
    PharmGKB entry for MAP2K4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MAP2K4 Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/map2k4/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MAP2K4 gene:
    Search GeneIP for patents involving MAP2K4

    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, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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