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

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)
About This Section

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

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

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 hereditary spastic paraplegia, and among its related super-pathways are Immune response BCR pathway and Development EGFR signaling via small GTPases. 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NT_010718.16  NC_018928.2  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for MAP2K4

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

UniProtKB/Swiss-Prot: 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
Subcellular location: Cytoplasm (By similarity). Nucleus (By similarity)
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:

  • UniProtKB: Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P45985

  • 4 DME Specific Peptides for MAP2K4 (P45985)
     WICMELM  FYGALFREGD  IKLCDFGISG  YDVRSDVWSLGITLYE 

    MAP2K4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    MAP2K4 Protein Expression
    REFSEQ proteins (2 alternative transcripts): 
    NP_001268364.1  NP_003001.1  

    ENSEMBL proteins: 
     ENSP00000262445   ENSP00000463507   ENSP00000410402   ENSP00000473582   ENSP00000473472  
     ENSP00000473606   ENSP00000473458   ENSP00000473511   ENSP00000467239   ENSP00000463854  
     ENSP00000463003   ENSP00000463834  
    Reactome Protein details: P45985
    Human Recombinant Protein Products for MAP2K4: 
    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 

    Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005829cytosol TAS--

    MAP2K4 for ontologies           About GeneDecksing



    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
    GenScript Custom Superior Antibodies Services for MAP2K4
    Novus Biologicals MAP2K4 Antibodies
    Abcam antibodies for MAP2K4
    Cloud-Clone Corp. Antibodies for MAP2K4 
    ThermoFisher Antibody for MAP2K4
    LSBio Antibodies in human, mouse, rat for MAP2K4 

    Assay Products for MAP2K4: 
    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)
    About This Section
    HGNC Gene Families: 
    MAP2K: Mitogen-activated protein kinase cascade / Kinase kinases

    IUPHAR Guide to PHARMACOLOGY protein family classification: mitogen-activated protein kinase kinase 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_cat_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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity TAS7716521
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding IPI9808624
    GO:0005524ATP binding IEA--
         
    MAP2K4 for ontologies           About GeneDecksing


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

         10 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Map2k4):
     behavior/neurological  cardiovascular system  cellular  growth/size  hematopoietic system 
     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 - Custom generated mouse model solutions for MAP2K4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions 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:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MAP2K4
    8/132 QIAGEN miScript miRNA 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:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for MAP2K4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MAP2K4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for MAP2K4
    Sirion Biotech Customized adenovirus for overexpression of MAP2K4

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    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
    Sirion Biotech Customized lentivirus for stable overexpression of MAP2K4 
                         Customized lentivirus expression plasmids for stable overexpression of MAP2K4 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for MAP2K4
    Search LifeMap BioReagents cell lines for MAP2K4
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP2K4


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

    SuperPaths for MAP2K4 About   (see all 100)                                                                                              See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Immune response Fc epsilon RI pathway
    Immune response Fc epsilon RI pathway0.45
    Fc-epsilon receptor I signaling in mast cells0.33
    Fc epsilon RI signaling pathway0.40
    2Development HGF signaling pathway
    Development HGF signaling pathway0.78
    Development EGFR signaling via PIP30.40
    Development EGFR signaling via small GTPases0.44
    Apoptosis and survival Anti-apoptotic action of membrane-bound ESR10.35
    Development PDGF signaling via MAPK cascades0.41
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)0.31
    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 pathway0.93
    Chagas disease (American trypanosomiasis)0.33
    Toll-like receptor signaling pathway0.93
    Hepatitis B0.31
    5Development EGFR signaling pathway
    Development EGFR signaling pathway0.87
    EGF Pathway0.41
    GDNF-Family Ligands and Receptor Interactions0.41

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5/29 EMD Millipore Pathways for MAP2K4 (see all 29)
        Apoptosis and survival FAS signaling cascades
    Immune response MIF in innate immunity response
    G-protein signaling G-Protein alpha-12 signaling pathway
    Immune response CCR3 signaling in eosinophils
    G-protein signaling Ras family GTPases in kinase cascades (scheme)

    4 R&D Systems Pathways for MAP2K4
        NOD-like Receptor Signaling Pathways
    Inflammasome Activation Pathways
    Toll-Like receptor Signaling Pathways
    TGF-beta Signaling Pathways

    5/87 Downloadable PowerPoint Slides of QIAGEN 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

    5/30 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

    5/29 BioSystems Pathways for MAP2K4 (see all 29)
        MAPK signaling pathway
    Apoptosis
    MicroRNAs in cardiomyocyte hypertrophy
    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

    5/27        Reactome Pathways for MAP2K4 (see all 27)
        FCERI mediated MAPK activation
    Toll Like Receptor 2 (TLR2) Cascade
    Toll Like Receptor TLR6:TLR2 Cascade
    Toll-Like Receptors Cascades
    TRAF6 Mediated Induction of proinflammatory cytokines

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

    5/12         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

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for MAP2K4

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

    5/634 Interacting proteins for MAP2K4 (P459851, 2, 3 ENSP000002624454) via UniProtKB, MINT, STRING, and/or I2D (see all 634)
    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): 5/21 biological process terms (GO ID links to tree view) (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade ----
    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--
    GO:0006468protein phosphorylation ----

    MAP2K4 for ontologies           About GeneDecksing



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

    MAP2K4 for compounds           About GeneDecksing

    EMD Millipore small molecules for MAP2K4:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    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--

    10/36 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)

    Search CenterWatch for drugs/clinical trials and news about MAP2K4 / MP2K4

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

    REFSEQ mRNAs for 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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    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 

    24/191 AceView cDNA sequences (see all 191):

    BM461511 BU178994 AA810268 C02290 Z44789 AV709279 BM718928 BQ690937 
    AI022560 Z40358 BQ688042 AU137540 T16655 CR601866 AU119785 AK122997 
    AI147099 AA258067 AU139238 BP377803 AA293050 AI613302 BC060764 AL133959 

    GeneLoc Exon Structure

    5/6 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™, 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

    MAP2K4 expression in normal human tissues (normalized intensities)      MAP2K4 embryonic expression: see
    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 
     5/5 selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 8 entries
             Thalamus
             ganglion/cranial   
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Peripheral Nervous System (Nervous System)
             spinal/ganglion/dorsal root ganglion   
     
     Spinal Cord (Nervous System)
             spinal/ganglion/dorsal root ganglion   
     
     Liver (Hepatobiliary System)
             Hepatoblasts Liver Bud

    See MAP2K4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MAP2K4

    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

        SABiosciences Expression via Pathway-Focused 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

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

    This gene was present in the common ancestor of animals and fungi.

    Orthologs for MAP2K4 gene from 8/21 species (see all 21)    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
    98.24(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 89.44(n)
    97.25(a)
      417312  XM_415583.3  XP_415583.3 
    lizard
    (Anolis carolinensis)
    Reptilia MAP2K46
    mitogen-activated protein kinase kinase 4
    75(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
    56.73(n)1
    62.33(a)1
      85A53
    410201  NM_001170080.11  NP_001163551.11 
    worm
    (Caenorhabditis elegans)
    Secernentea sek-13
    mkk-41
    SER/THR-protein kinase3
    Protein MKK-41
    51(a)
    (best of 4)3
    57.65(n)1
    55.14(a)1
      X(7852049-7854578)3
    1856821  NM_077281.31  NP_509682.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes PBS21 Pbs2p 50.77(n)
    44.74(a)
      853313   NP_012407.2 


    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)
    About This Section
    Paralogs for MAP2K4 gene
    MAP2K32  MAP2K52  MAP2K22  MAP2K62  MAP2K72  MAP2K12  
    18/19 SIMAP similar genes for MAP2K4 using alignment to 8 protein entries:     MP2K4_HUMAN (see all proteins) (see all similar genes):
    MAP2K6    DKFZp686N0154    STK38L    MAP2K3    MAP2K7    PHKG2
    MAP2K5    STK25    DKFZp686L02273    MAPK3    MAP2K2    RPS6KA2
    RPS6KA1    STK3    STK4    MAP2K1    MAP4K1    MAP4K5

    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) 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

    10/2328 SNPs in MAP2K4 are shown (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 SABiosciences Cancer Mutation PCR Assays for MAP2K4:
    Cosmic IdAA Change
    79380p.R110*
    20411p.R154W
    26108p.S280*
    26105p.S184L
    1 SABiosciences qBiomarker Copy Number PCR Array containing MAP2K4:
    Kinases & Phosphatases
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 601335    OMIM disorders: --

    20/47 diseases for MAP2K4 (see all 47):    About MalaCards
    hypertrophic scars    hereditary spastic paraplegia    pancreatic endocrine tumor    paraplegia
    trypanosomiasis    huntington's disease    chagas disease    laryngeal squamous cell carcinoma
    cytomegalovirus infection    gastric adenocarcinoma    spasticity    prostate cancer, progression of
    sjogren's syndrome    prostate cancer    laryngitis    rhabdomyosarcoma
    pancreatitis    pancreatic cancer    malignant glioma    adenocarcinoma


    MAP2K4 for disorders           About GeneDecksing


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

    10/21 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)
    About This Section

    PubMed articles for MAP2K4 gene, integrated from 9 sources (see all 394):
    (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. (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. (1998)
    3. The association between -1304T>G polymorphism in t he 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. (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. (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. (1995)
    6. The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. (PubMed id 21333379)1, 2 Haeusgen W.... Waetzig V. (2011)
    7. Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition st ate. (PubMed id 20732303)1, 2 Matsumoto T....Tada T. (2010)
    8. A functional variant (-1304T>G) in the MKK4 promot er contributes to a decreased risk of lung cancer by increasing the promoter ac tivity. (PubMed id 20554746)1, 4 Liu B....Lu J. (2010)
    9. Diverse physiological functions of MKK4 and MKK7 during early embryogenesis. (PubMed id 20801953)1, 2 Asaoka Y. and Nishina H. (2010)
    10. Genetic mutations associated with cigarette smoking in pancreatic cancer. (PubMed id 19351817)1, 4 Blackford A....Hruban R.H. (2009)

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

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

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 6416 HGNC: 6844 AceView: MAP2K4 Ensembl:ENSG00000065559 euGenes: HUgn6416
    ECgene: MAP2K4 Kegg: 6416 H-InvDB: MAP2K4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for 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.)
    About This Section
    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



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    About This Section

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     lentivirus expression plasmids for stable overexpression of MAP2K4
     adenovirus for overexpression of MAP2K4
     LSBio Antibodies in human, mouse, rat for MAP2K4
    Customized transgenic rodents for:
     Humanization
     Biomarker expression
     Off-target effect monitoring
     Translational medicine
     Tissue-specific gene expresssion
     Time-controlled gene expresssion
           
    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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