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    Map3k4 mitogen-activated protein kinase kinase kinase 4 [ Mus musculus (house mouse) ]

    Gene ID: 26407, updated on 12-May-2024

    Summary

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    Official Symbol
    Map3k4provided by MGI
    Official Full Name
    mitogen-activated protein kinase kinase kinase 4provided by MGI
    Primary source
    MGI:MGI:1346875
    See related
    Ensembl:ENSMUSG00000014426 AllianceGenome:MGI:1346875
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Tas; MTK1; RP17; Mek4b; Mekk4; Rp17a; MEKK 4; D17Rp17; MAPKKK4; D17Rp17e; mKIAA0213
    Summary
    Enables protein kinase activity. Involved in intracellular signal transduction and positive regulation of JUN kinase activity. Acts upstream of or within several processes, including chorionic trophoblast cell differentiation; male germ-line sex determination; and placenta development. Located in cytoplasm. Is expressed in several structures, including central nervous system; future brain; and genitourinary system. Orthologous to human MAP3K4 (mitogen-activated protein kinase kinase kinase 4). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in CNS E11.5 (RPKM 4.2), ovary adult (RPKM 4.2) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    17 8.42 cM; 17 A1
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 17 NC_000083.7 (12446508..12537683, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 17 NC_000083.6 (12227621..12318796, complement)

    Chromosome 17 - NC_000083.7Genomic Context describing neighboring genes Neighboring gene parkin RBR E3 ubiquitin protein ligase Neighboring gene STARR-seq mESC enhancer starr_41840 Neighboring gene STARR-seq mESC enhancer starr_41841 Neighboring gene predicted gene, 46604 Neighboring gene STARR-seq mESC enhancer starr_41845 Neighboring gene CapStarr-seq enhancer MGSCv37_chr17:12311592-12311701 Neighboring gene STARR-positive B cell enhancer ABC_E4192 Neighboring gene STARR-seq mESC enhancer starr_41846 Neighboring gene STARR-seq mESC enhancer starr_41847 Neighboring gene STARR-seq mESC enhancer starr_41848 Neighboring gene VISTA enhancer mm156 Neighboring gene STARR-positive B cell enhancer mm9_chr17:12398581-12398882 Neighboring gene 1-acylglycerol-3-phosphate O-acyltransferase 4 Neighboring gene teratocarcinoma-derived growth factor, pseudogene 2 Neighboring gene STARR-seq mESC enhancer starr_41854 Neighboring gene RIKEN cDNA 4732491K20 gene Neighboring gene predicted gene, 46605 Neighboring gene predicted gene, 24794 Neighboring gene serologically defined colon cancer antigen 3 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure. Mizote I, et al. J Mol Cell Cardiol, 2010 Feb. PMID 19850048
    2. MEKK4 regulates developmental EMT in the embryonic heart. Stevens MV, et al. Dev Dyn, 2006 Oct. PMID 16894626
    3. LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4. Zhou H, et al. FASEB J, 2021 Jan. PMID 33184917
    4. MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition. Mobley RJ, et al. Cell Rep, 2017 Mar 7. PMID 28273454, Free PMC Article
    5. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4. Bullard SA, et al. J Biol Chem, 2016 Aug 19. PMID 27358404, Free PMC Article

    See all (82) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway.
      Title: MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway.
    2. MAP3K4 kinase activity dependent control of mouse gonadal sex determinationdagger.
      Title: MAP3K4 kinase activity dependent control of mouse gonadal sex determination†.
    3. LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4.
      Title: LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4.
    4. MAP3K4 activity controls epithelial-to-mesenchymal transition through the ubiquitination and degradation of HDAC6.
      Title: MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition.
    5. by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy.
      Title: Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.
    6. Map3k4 haploinsufficiency is the cause of T-associated sex reversal.
      Title: Transgenic expression of Map3k4 rescues T-associated sex reversal (Tas) in mice.
    7. suggest a requirement for GADD45gamma in promoting MAP3K4-mediated activation of p38 MAPK signaling in embryonic gonadal somatic cells for testis determination
      Title: Gadd45γ and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression.
    8. regulates epithelial-mesenchymal transition in trophoblast stem cells
      Title: MAP3K4/CBP-regulated H2B acetylation controls epithelial-mesenchymal transition in trophoblast stem cells.
    9. MTK1 plays an important role in the regulation of cell death and is also involved in the pathogenesis of heart failure.
      Title: Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure.
    10. a role for the signalling pathway in mouse sex determination
      Title: Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) reveals a requirement for MAPK signalling in mouse sex determination.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase kinase kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within chorionic trophoblast cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within determination of dorsal identity ISO
    Inferred from Sequence Orthology
    more info
    		 PubMed 
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within male germ-line sex determination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within placenta development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of JUN kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of JUN kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of p38MAPK cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of telomerase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of telomere capping ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of telomere maintenance via telomerase ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to UV-C ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 4
    Names
    MAPK/ERK kinase kinase 4
    MEK kinase 4
    T-associated sex reversal
    NP_001344651.1
    NP_036078.2
    XP_030105679.1
    XP_030105680.1
    XP_036016515.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001357722.1 → NP_001344651.1  mitogen-activated protein kinase kinase kinase 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC136921, CO040910
      Consensus CDS
      CCDS88991.1
      UniProtKB/TrEMBL
      Q8K4X6
      Related
      ENSMUSP00000156730.2, ENSMUST00000233755.2
      Conserved Domains (1) summary
      cd06626
      Location:1279 → 1538
      STKc_MEKK4; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4

    2. NM_011948.2 → NP_036078.2  mitogen-activated protein kinase kinase kinase 4 isoform 1

      See identical proteins and their annotated locations for NP_036078.2

      Status: VALIDATED

      Source sequence(s)
      BC058719, CK634503
      Consensus CDS
      CCDS37435.1
      UniProtKB/Swiss-Prot
      O08648, O08649, O70124, Q6PDG6
      UniProtKB/TrEMBL
      Q80U64
      Related
      ENSMUSP00000086459.6, ENSMUST00000089058.7
      Conserved Domains (2) summary
      smart00220
      Location:1332 → 1590
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06626
      Location:1331 → 1590
      STKc_MEKK4; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000083.7 Reference GRCm39 C57BL/6J

      Range
      12446508..12537683 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_030249820.2 → XP_030105680.1  mitogen-activated protein kinase kinase kinase 4 isoform X3

      UniProtKB/TrEMBL
      Q80U64
      Conserved Domains (1) summary
      cd06626
      Location:1222 → 1481
      STKc_MEKK4; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4

    2. XM_030249819.2 → XP_030105679.1  mitogen-activated protein kinase kinase kinase 4 isoform X2

      UniProtKB/TrEMBL
      Q80U64
      Conserved Domains (1) summary
      cd06626
      Location:1284 → 1543
      STKc_MEKK4; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4

    3. XM_036160622.1 → XP_036016515.1  mitogen-activated protein kinase kinase kinase 4 isoform X1

      UniProtKB/TrEMBL
      Q80U64
      Conserved Domains (1) summary
      cd06626
      Location:1321 → 1580
      STKc_MEKK4; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O08648.2 GenPept UniProtKB/Swiss-Prot:O08648

    Gene LinkOut

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