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

Gene ID: 26407, updated on 5-Mar-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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See Map3k4 in Genome Data Viewer
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

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