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MAP3K4 Gene

protein-coding   GIFtS: 67
GCID: GC06P161412

Mitogen-Activated Protein Kinase Kinase Kinase 4


(Previous symbol: MEKK4)
  Search for MAP3K4
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Mitogen-Activated Protein Kinase Kinase Kinase 41 2     PRO04122
MEKK41 2 3 5     DJ473J16.1 (Mitogen-Activated Protein Kinase Kinase Kinase 4)2
MAPKKK42 3 5     MAP/ERK Kinase Kinase 42
MTK12 3 5     Predicted Protein Of HQ04122
MAP Three Kinase 12 3     SSK2/SSK22 MAP Kinase Kinase Kinase, Yeast, Homolog Of2
MAPK/ERK Kinase Kinase 42 3     EC 2.7.11.253
MEK Kinase 42 3     KIAA02133
MEKK 42 3     

External Ids:    HGNC: 68561   Entrez Gene: 42162   Ensembl: ENSG000000855117   OMIM: 6024255   UniProtKB: Q9Y6R43   

Export aliases for MAP3K4 gene to outside databases

Previous GC identifers: GC06P160766 GC06P161286 GC06P161322 GC06P161383 GC06P161332 GC06P158868


(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 MAP3K4 Gene:
The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein
kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK),
which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and
JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and
inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a
protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory
domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK
pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate
PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that
activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a
minor mediator of the JNK pathway. Two alternatively spliced transcripts encoding distinct isoforms have been
described. (provided by RefSeq, Jul 2008)

GeneCards Summary for MAP3K4 Gene:
MAP3K4 (mitogen-activated protein kinase kinase kinase 4) is a protein-coding gene. GO annotations related to this gene include MAP kinase kinase kinase activity and protein kinase activity.

UniProtKB/Swiss-Prot: M3K4_HUMAN, Q9Y6R4
Function: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK
pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6

Gene Wiki entry for MAP3K4 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_000006.12  NT_025741.16  NC_018917.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the MAP3K4 gene promoter:
         Egr-3   Spz1   NRSF form 1   MyoD   AP-4   NRSF form 2   aMEF-2   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMAP3K4 promoter sequence
   Search Chromatin IP Primers for MAP3K4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MAP3K4


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

Entrez Gene cytogenetic band: 6q26   Ensembl cytogenetic band:  6q26   HGNC cytogenetic band: 6q26

MAP3K4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MAP3K4 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P161412:  view genomic region     (about GC identifiers)

Start:
161,412,759 bp from pter      End:
161,538,417 bp from pter
Size:
125,659 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: M3K4_HUMAN, Q9Y6R4 (See protein sequence)
Recommended Name: Mitogen-activated protein kinase kinase kinase 4  
Size: 1608 amino acids; 181685 Da
Cofactor: Magnesium
Subunit: Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes
homodimerization (By similarity). Binds both upstream activators and downstream substrates in multimolecular
complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1
Sequence caution: Sequence=BAA13204.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Sequence=CAC12766.2; Type=Erroneous gene model prediction; Sequence=CAH70639.1; Type=Erroneous gene model
prediction; Sequence=CAH70640.1; Type=Erroneous gene model prediction; Sequence=CAI20815.1; Type=Erroneous gene
model prediction; Sequence=CAI20816.1; Type=Erroneous gene model prediction; Sequence=CAI21477.1; Type=Erroneous
gene model prediction; Sequence=CAI41309.1; Type=Erroneous gene model prediction; Sequence=CAI41310.1;
Type=Erroneous gene model prediction;
Secondary accessions: A6H8W0 B7ZLD3 B9EG75 Q5VTT8 Q5VTT9 Q92612 Q9H408
Alternative splicing: 2 isoforms:  Q9Y6R4-1   Q9Y6R4-2   

Explore the universe of human proteins at neXtProt for MAP3K4: NX_Q9Y6R4

Explore proteomics data for MAP3K4 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See MAP3K4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_005913.2  NP_006715.2  

    ENSEMBL proteins: 
     ENSP00000355886   ENSP00000439377   ENSP00000375986   ENSP00000355887   ENSP00000297332  
     ENSP00000445018   ENSP00000446303   ENSP00000390508  

    MAP3K4 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for MAP3K4
    OriGene Custom MassSpec
    OriGene Custom Protein Services for MAP3K4
    GenScript Custom Purified and Recombinant Proteins Services for MAP3K4
    Novus Biologicals MAP3K4 Protein
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for MAP3K4

     
    Search eBioscience for Proteins for MAP3K4 

    MAP3K4 Antibody Products:

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    Abcam antibodies for MAP3K4
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    Search ThermoFisher Antibodies for MAP3K4
    LSBio Antibodies in human, mouse, rat for MAP3K4

    MAP3K4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Cloud-Clone Corp. ELISAs for MAP3K4
    Cloud-Clone Corp. CLIAs for MAP3K4
    Search eBioscience for ELISAs for MAP3K4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    MAP3K: Mitogen-activated protein kinase cascade / Kinase kinase kinases

    IUPHAR Guide to PHARMACOLOGY protein family classification: mitogen-activated protein kinase kinase kinase 4
    STE11 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 Q9Y6R4

    ProtoNet protein and cluster: Q9Y6R4

    UniProtKB/Swiss-Prot: M3K4_HUMAN, Q9Y6R4
    Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase
    subfamily
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with MAP3K4           About GenesLikeMe


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

         UniProtKB/Swiss-Prot Summary: M3K4_HUMAN, Q9Y6R4
    Function: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK
    pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase
    activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by
    binding to the N-terminal domain. Activated by phosphorylation on Thr-1505

         Genatlas biochemistry entry for MAP3K4:
    mitogen activated protein (MAP/ERK) kinase kinase kinase 4,major mediator of environnemtal stress,activating the
    MAPK and JNK signal transduction pathway (see MAP4K4)

         Enzyme Number (IUBMB): EC 2.7.11.251

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity ----
    GO:0004709MAP kinase kinase kinase activity IDA9305639
    GO:0004713protein tyrosine kinase activity ----
    GO:0005515protein binding IPI12052864
         
    Find genes that share ontologies with MAP3K4           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for MAP3K4:
     Decreased telomerase activity  Decreased viability  Increased apoptosis  Increased cell death in DLD-1  

         11 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Map3k4):
     embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  limbs/digits/tail  mortality/aging  nervous system  reproductive system 
     skeleton 

    Find genes that share phenotypes with MAP3K4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Map3k4tm1Flv for MAP3K4

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for MAP3K4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for MAP3K4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for MAP3K4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for MAP3K4

    miRNA
    Products:
        
    miRTarBase miRNAs that target MAP3K4:
    hsa-mir-124-3p (MIRT022893), hsa-mir-148a-3p (MIRT048040), hsa-mir-92a-3p (MIRT049769), hsa-mir-93-5p (MIRT048846)

    Block miRNA regulation of human, mouse, rat MAP3K4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate MAP3K4 (see all 21):
    hsa-miR-148b hsa-miR-199b-3p hsa-miR-199a-3p hsa-miR-15a hsa-miR-3129-5p hsa-miR-144 hsa-miR-424 hsa-miR-195
    SwitchGear 3'UTR luciferase reporter plasmidMAP3K4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for MAP3K4
    Predesigned siRNA for gene silencing in human, mouse, rat MAP3K4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for MAP3K4

    Clone
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    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): MAP3K4 (NM_006724)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MAP3K4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MAP3K4

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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MAP3K4


    (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
    M3K4_HUMAN, Q9Y6R4: Cytoplasm, perinuclear region (By similarity). Note=Localized in perinuclear vesicular-like
    structures, probably Golgi-associated vesicles (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol3
    lysosome1
    nucleus1
    vacuole1

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA9827804
    GO:0048471perinuclear region of cytoplasm IEA--

    Find genes that share ontologies with MAP3K4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for MAP3K4 About   (see all 41)  
    See pathways by source

    SuperPathContained pathways About
    1MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    2Development Endothelin 1 EDNRA signaling
    Development Endothelin 1 EDNRA signaling0.41
    GnRH signaling pathway0.38
    3ErbB4 Pathway
    LPS Stimulated MAPK Signaling0.47
    PACAP Signaling0.37
    FGF Pathway0.37
    4NGF Pathway
    TRKA Signaling0.75
    NGF Pathway0.75
    5NF-KappaB Family Pathway
    NF-KappaB (p50-p65) Pathway0.72
    NF-KappaB Family Pathway0.72


    Find genes that share SuperPaths with MAP3K4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for MAP3K4 (see all 33)
        Antioxidant Action of Vitamin-C
    Interferon Pathway
    TRKA Signaling
    JNK Pathway
    PACAP Signaling

    Selected GeneGo (Thomson Reuters) Pathways for MAP3K4 (see all 13)
        Development A2A receptor signaling
    Development Beta-adrenergic receptors signaling via cAMP
    Development Endothelin-1/EDNRA signaling
    G-protein signaling Regulation of p38 and JNK signaling mediated by G-proteins
    Immune response IL-12-induced IFN-gamma production

    Selected BioSystems Pathways for MAP3K4 (see all 8)
        MAPK signaling pathway
    EGFR1 Signaling Pathway
    Insulin Signaling
    G13 Signaling Pathway
    DNA damage response (only ATM dependent)


    2 Kegg Pathways  (Kegg details for MAP3K4):
        MAPK signaling pathway
    GnRH signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Array including MAP3K4: 
              MAP Kinase (MAPK) Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MAP3K4

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

    Selected Interacting proteins for MAP3K4 (Q9Y6R41, 2, 3 ENSP000003759864) via UniProtKB, MINT, STRING, and/or I2D (see all 195)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SH3KBP1Q96B971, 2, 3, ENSP000003809214EBI-448104,EBI-346595 MINT-7186852 MINT-7186967 MINT-7187506 MINT-7186667 MINT-7187190 I2D: score=2 STRING: ENSP00000380921
    FLNBO753691, 2, 3, ENSP000002959564EBI-448104,EBI-352089 MINT-7288768 MINT-7288733 I2D: score=1 STRING: ENSP00000295956
    PTK2BQ142892, 3, ENSP000003328164MINT-51385 MINT-51384 I2D: score=3 STRING: ENSP00000332816
    ANXA2P073552, 3, ENSP000003460324MINT-51382 I2D: score=3 STRING: ENSP00000346032
    DDX39BQ138383I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade IDA9305639
    GO:0000186activation of MAPKK activity IDA9305639
    GO:0001890placenta development IEA--
    GO:0006468protein phosphorylation ----
    GO:0010225response to UV-C IMP9305639

    Find genes that share ontologies with MAP3K4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    Selected ApexBio Compounds for MAP3K4 (see all 23)     About this table
    CompoundAction CAS #
    AZD6244 (Selumetinib)Potent, selective, and ATP-uncompetitive MEK inhibitor--
    AZD8330orally active, selective MEK inhibitor[869357-68-6]
    BIX 02188MEK5-selective inhibitor[1094614-84-2]
    BIX 02189blocks MEK5 and ERK5 catalytic activity[1094614-85-3]
    Cobimetinibselective inhibitor of MEK[934660-93-2]
    FR 180204Selective ERK inhibitor[865362-74-9]
    MEK inhibitorPotent MEK inhibitor, Antitumor agent[334951-92-7]
    MEK162 (ARRY-162, ARRY-438162)orally available inhibitor of MEK1/2[606143-89-9]
    PD0325901MEK inhibitor[391210-10-9]
    PD184352 (CI-1040)Selective MEK inhibitor[212631-79-3]

    Browse Tocris compounds for MAP3K4 (M3K4)

    3 HMDB Compounds for MAP3K4    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--
    MagnesiumMagnesium (see all 2)7439-95-4--

    1 Novoseek inferred chemical compound relationship for MAP3K4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 0 5 15601262 (4)



    Find genes that share compounds with MAP3K4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MAP3K4 gene (2 alternative transcripts): 
    NM_005922.2  NM_006724.2  

    Unigene Cluster for MAP3K4:

    Mitogen-activated protein kinase kinase kinase 4
    Hs.390428  [show with all ESTs]
    Unigene Representative Sequence: NM_005922
    16 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000366919(uc003qto.3 uc003qtp.3) ENST00000542952 ENST00000392142(uc010kkc.1 uc003qtn.3 uc011efz.2 uc011ega.2)
    ENST00000366920 ENST00000348824 ENST00000544041 ENST00000490904 ENST00000448119
    ENST00000446500 ENST00000542851 ENST00000540205 ENST00000543421 ENST00000541901
    ENST00000544733 ENST00000536852(uc003qtq.3) ENST00000539610
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate MAP3K4 (see all 21):
    hsa-miR-148b hsa-miR-199b-3p hsa-miR-199a-3p hsa-miR-15a hsa-miR-3129-5p hsa-miR-144 hsa-miR-424 hsa-miR-195
    SwitchGear 3'UTR luciferase reporter plasmidMAP3K4 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat MAP3K4
    Clone
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    OriGene ORF clones in mouse, rat for MAP3K4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): MAP3K4 (NM_006724)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MAP3K4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MAP3K4
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for MAP3K4
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat MAP3K4
      QuantiTect SYBR Green Assays in human, mouse, rat MAP3K4
      QuantiFast Probe-based Assays in human, mouse, rat MAP3K4

    Additional mRNA sequence: 

    AF002715.1 AF116604.1 AK124430.1 AK307866.1 BC136276.1 BC143735.1 BC143743.1 BC143750.1 
    BC146770.1 D86968.2 

    13 DOTS entries:

    DT.450615  DT.100813358  DT.95329707  DT.100540  DT.114201  DT.435317  DT.95137335  DT.95103363 
    DT.95296284  DT.100674662  DT.121372195  DT.75111096  DT.95312405 

    Selected AceView cDNA sequences (see all 125):

    BQ446855 AU121956 BQ028872 AF116604 BF794038 NM_006724 CD358176 AI566955 
    BX503009 NM_005922 AI055806 AI061643 AI215795 BM817868 AI336266 AA317854 
    AA402447 BM719813 AI051200 D86968 BM703670 BU730102 BQ049757 BQ228725 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K4 (see all 11)    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17 ^ 18 ^
    SP1:                                                                                                  -     -           -     -                                 
    SP2:                                                                                                                                                            
    SP3:                                                                                                        -           -     -                                 
    SP4:                                                                                                                          -                                 
    SP5:                    -                                                                                                                                       

    ExUns: 19a · 19b ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25
    SP1:        -     -                                 
    SP2:        -     -                                 
    SP3:                                                
    SP4:                                                
    SP5:                                                


    ECgene alternative splicing isoforms for MAP3K4

    (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)
    About This Section

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    MAP3K4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTAAGTGCCA
    MAP3K4 Expression
    About this image

    MAP3K4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MAP3K4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.390428

    UniProtKB/Swiss-Prot: M3K4_HUMAN, Q9Y6R4
    Tissue specificity: Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels
    in other tissues

        Pathway & Disease-focused RT2 Profiler PCR Array including MAP3K4: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for MAP3K4 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Map3k41 , 5 mitogen-activated protein kinase kinase kinase 41, 5 83.67(n)1
    89.6(a)1
      17 (8.42 cM)5
    264071  NM_011948.21  NP_036078.21 
     122276215 
    chicken
    (Gallus gallus)
    Aves MAP3K41 mitogen-activated protein kinase kinase kinase 4 80.69(n)
    86.45(a)
      421579  XM_004935561.1  XP_004935618.1 
    lizard
    (Anolis carolinensis)
    Reptilia MAP3K46
    mitogen-activated protein kinase kinase kinase 4
    82(a)
    1 ↔ 1
    1(211666769-211745235)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.158632 Xenopus laevis transcribed sequence with strong similarity more 79.65(n)    CB208399.1 
    zebrafish
    (Danio rerio)
    Actinopterygii map3k41 mitogen activated protein kinase kinase kinase 4 66.87(n)
    72.92(a)
      325488  XM_005157017.1  XP_005157074.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Mekk11 , 3 protein amino acid phosphorylation
    receptor signaling more3
    Mekk11
    50(a)3
    45.83(n)1
    37.41(a)1
      91C53
    422531  NM_142493.31  NP_650750.41 
    worm
    (Caenorhabditis elegans)
    Secernentea mtk-13   -- 36(a)   I(5803701-5809423)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes SSK2(YNR031C)4 MAP kinase kinase kinase of the HOG1 mitogen-activated more   --   14(685433-680694) 855765  NP_014428.1 


    ENSEMBL Gene Tree for MAP3K4 (if available)
    TreeFam Gene Tree for MAP3K4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MAP3K4 gene
    Selected SIMAP similar genes for MAP3K4 using alignment to 7 protein entries:     M3K4_HUMAN (see all proteins) (see all similar genes):
    NEK9    MAP4K3    MAP3K2    CDKL1    MST094    MAP4K5
    NEK3    DKFZp564L2416    MAPK8    TRIB1    RPS6KA2    NEK6
    NEK7    STK25    BRAF    PAK1    MAP3K11    PAK4

    Find genes that share paralogs with MAP3K4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MAP3K4 (see all 2817)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0406914
    An ovarian serous carcinoma sample4--see VAR_0406912 E Q mis40--------
    rs1450467071,2
    --161410840(+) TTACTA/GAGTTC 2 -- us2k10--------
    rs1863631351,2
    C--161410853(+) CTAACA/GCCATG 2 -- us2k10--------
    rs1911518561,2
    --161410871(+) CCAGAA/GACATT 2 -- us2k10--------
    rs6105381,2
    C,F,A,H--161410911(+) AGAACG/AGCTTC 2 -- us2k111Minor allele frequency- A:0.33NA WA CSA EA 373
    rs6106381,2
    C,F,A,H--161410978(+) TGAGGC/AGCTCA 2 -- us2k111Minor allele frequency- A:0.50NA WA CSA EA 373
    rs1807299691,2
    --161411056(+) TTTCCG/TGGACC 2 -- us2k10--------
    rs1865787781,2
    --161411068(+) AGCATC/GGGGGT 2 -- us2k10--------
    rs1910295821,2
    --161411087(+) AAGTCA/CCAACA 2 -- us2k10--------
    rs1388348381,2
    --161411097(+) ACTTAC/TATTGA 2 -- us2k10--------

    HapMap Linkage Disequilibrium report for MAP3K4 (161412759 - 161538417 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for MAP3K4 (see all 11):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2733068CNV Deletion23290073
    esv2733067CNV Deletion23290073
    esv2287098CNV Deletion18987734
    esv2733070CNV Deletion23290073
    esv5229CNV Deletion18987735
    esv1009798CNV Deletion20482838
    esv2733069CNV Deletion23290073
    esv1022211CNV Deletion17803354
    esv2733071CNV Deletion23290073
    esv2422347CNV Duplication17116639

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602425    OMIM disorders: --

    1 disease from the University of Copenhagen DISEASES database for MAP3K4:
    Nicotine dependence

    Find genes that share disorders with MAP3K4           About GenesLikeMe

    1 Novoseek inferred disease relationship for MAP3K4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    shock 15.7 1 9305639 (1)

    Genetic Association Database (GAD): MAP3K4
    Human Genome Epidemiology (HuGE) Navigator: MAP3K4 (1 document)

    Export disorders for MAP3K4 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 MAP3K4 gene, integrated from 10 sources (see all 55):
    (articles sorted by number of sources associating them with MAP3K4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways. (PubMed id 9305639)1, 2, 3, 9 Takekawa M.... Saito H. (EMBO J. 1997)
    2. MEKK4 is an effector of the embryonic TRAF4 for JNK activation. (PubMed id 16157600)1, 2, 9 Abell A.N. and Johnson G.L. (J. Biol. Chem. 2005)
    3. The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. (PubMed id 15262978)1, 2, 9 Wong C.K.... Lin S.-C. (J. Biol. Chem. 2004)
    4. Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes. (PubMed id 20624154)1, 4 Grucza R.A....Bierut L.J. (Addict Biol 2010)
    5. Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding. (PubMed id 12052864)1, 2 Mita H.... Saito H. (Mol. Cell. Biol. 2002)
    6. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. (PubMed id 9039502)1, 2 Nagase T.... Nomura N. (DNA Res. 1996)
    7. Interferon-gamma-dependent tyrosine phosphorylation of MEKK4 via Pyk2 is regulated by annexin II and SHP2 in keratinocytes. (PubMed id 15601262)1, 9 Halfter U.M....Vaillancourt R.R. (Biochem. J. 2005)
    8. CIN85 regulates the ability of MEKK4 to activate the p38 MAP kinase pathway. (PubMed id 16256071)1, 9 Aissouni Y.... Soubeyran P. (Biochem. Biophys. Res. Commun. 2005)
    9. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. (PubMed id 9827804)1, 9 Takekawa M. and Saito H. (Cell 1998)
    10. Phosphorylation of human tristetraprolin in response to its interaction with the Cbl interacting protein CIN85. (PubMed id 20221403)1, 9 Kedar V.P....Blackshear P.J. (PLoS ONE 2010)

    (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: 4216 HGNC: 6856 AceView: MAP3K4 Ensembl:ENSG00000085511 euGenes: HUgn4216
    ECgene: MAP3K4 Kegg: 4216 H-InvDB: MAP3K4

    (According to HUGE)
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    HUGE: KIAA0213

    (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 MAP3K4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MAP3K4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MAP3K4 gene:
    Search GeneIP for patents involving MAP3K4

    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, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, 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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