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Map3k3 mitogen-activated protein kinase kinase kinase 3 [ Mus musculus (house mouse) ]

Gene ID: 26406, updated on 27-Nov-2024

Summary

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Official Symbol
Map3k3provided by MGI
Official Full Name
mitogen-activated protein kinase kinase kinase 3provided by MGI
Primary source
MGI:MGI:1346874
See related
Ensembl:ENSMUSG00000020700 AllianceGenome:MGI:1346874
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
Mekk3; MAPKKK3; mKIAA4031
Summary
Predicted to enable protein serine/threonine kinase activity. Acts upstream of or within blood vessel development and positive regulation of p38MAPK cascade. Predicted to be active in cytoplasm. Is expressed in several structures, including early conceptus; heart; and metanephros. Orthologous to human MAP3K3 (mitogen-activated protein kinase kinase kinase 3). [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in lung adult (RPKM 22.2), subcutaneous fat pad adult (RPKM 19.2) and 28 other tissues See more
Orthologs
human all
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Genomic context

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See Map3k3 in Genome Data Viewer
Location:
11 E1; 11 68.89 cM
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 11 NC_000077.7 (105975358..106047482)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 11 NC_000077.6 (106084587..106156656)

Chromosome 11 - NC_000077.7Genomic Context describing neighboring genes Neighboring gene DDB1 and CUL4 associated factor 7 Neighboring gene translational activator of mitochondrially encoded cytochrome c oxidase I, opposite strand Neighboring gene CapStarr-seq enhancer MGSCv37_chr11:105927234-105927440 Neighboring gene STARR-seq mESC enhancer starr_30915 Neighboring gene STARR-positive B cell enhancer ABC_E2372 Neighboring gene translational activator of mitochondrially encoded cytochrome c oxidase I Neighboring gene STARR-positive B cell enhancer ABC_E258 Neighboring gene STARR-seq mESC enhancer starr_30916 Neighboring gene CapStarr-seq enhancer MGSCv37_chr11:106020710-106020950 Neighboring gene predicted gene 10840 Neighboring gene LIM domain containing 2 Neighboring gene STE20-related kinase adaptor alpha Neighboring gene STARR-positive B cell enhancer ABC_E7078 Neighboring gene STARR-positive B cell enhancer ABC_E739

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. Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations. Ren J, et al. Brain, 2023 Sep 1. PMID 36995941, Free PMC Article
  2. MEKK3 is required for lysophosphatidic acid-induced NF-kappaB activation. Sun W, et al. Cell Signal, 2009 Oct. PMID 19465115, Free PMC Article
  3. Regulation of NF-kappaB-dependent T cell activation and development by MEKK3. Shinohara H, et al. Int Immunol, 2009 Apr. PMID 19223432
  4. MEKK3 overexpression contributes to the hyperresponsiveness of IL-12-overproducing cells and CD4+ T conventional cells in nonobese diabetic mice. Zhang J, et al. J Immunol, 2010 Sep 15. PMID 20720201
  5. Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation. Schmidt C, et al. Mol Cell, 2003 Nov. PMID 14636585

See all (62) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations.
    Title: Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations.
  2. Endothelial hyperactivation of mutant MAP3K3 induces cerebral cavernous malformation enhanced by PIK3CA GOF mutation.
    Title: Endothelial hyperactivation of mutant MAP3K3 induces cerebral cavernous malformation enhanced by PIK3CA GOF mutation.
  3. MEKK3 activates IRF7 to trigger a potent type I interferon induction in response to TLR7/9 signaling.
    Title: MEKK3 activates IRF7 to trigger a potent type I interferon induction in response to TLR7/9 signaling.
  4. results suggest that MEKK3 plays important roles in platelet MAPK activation
    Title: Platelet MEKK3 regulates arterial thrombosis and myocardial infarct expansion in mice.
  5. The expression of MEKK3 in the midbrain is regulated by microRNA-124 in an experimental model of Parkinson's disease.
    Title: MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson's disease.
  6. this study shows that TAK1 negatively regulates lipopolysaccharide-induced cytokine secretion in myeloid cells by inhibiting MEKK3 activities
    Title: TAK1 knockdown enhances lipopolysaccharide-induced secretion of proinflammatory cytokines in myeloid cells via unleashing MEKK3 activity.
  7. endothelial-specific loss of Mekk3, Klf2 or Klf4 markedly prevents cerebral cavernous malformation lesion formation, reverses the increase in Rho activity, and rescues lethality
    Title: Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling.
  8. CCM2:MEKK3-mediated regulation of Rho-ROCK signalling is required for maintenance of neurovascular integrity, a mechanism by which CCM2 loss leads to disease.
    Title: Structure and vascular function of MEKK3-cerebral cavernous malformations 2 complex.
  9. NBR1 is increased in adipose tissue macrophages in obese mice. The NBR1-MEKK3 complex is important in JNK activation in macrophages.
    Title: A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose tissue inflammation in obesity.
  10. reveal a molecular mechanism by which CCM signaling controls endothelial gene expression during cardiovascular development
    Title: The cerebral cavernous malformation pathway controls cardiac development via regulation of endocardial MEKK3 signaling and KLF expression.
Submit: New GeneRIF Correction See all GeneRIFs (27)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Endonuclease-mediated (4) 
  • Targeted (6)  1 citation

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

Clone Names

  • KIAA4031

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables JUN kinase kinase kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity ISO
Inferred from Sequence Orthology
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within blood vessel development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within intracellular signal transduction ISO
Inferred from Sequence Orthology
more info
 PubMed 
involved_in negative regulation of cellular senescence ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of canonical NF-kappaB signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell migration involved in sprouting angiogenesis ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of cell proliferation in bone marrow ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within positive regulation of p38MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within protein autophosphorylation ISO
Inferred from Sequence Orthology
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 3
Names
MAPK/ERK kinase kinase 3
MEK kinase 3
MEKK 3
NP_036077.1
XP_011247339.1
XP_036012603.1
XP_036012604.1

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_011947.4 → NP_036077.1  mitogen-activated protein kinase kinase kinase 3

    See identical proteins and their annotated locations for NP_036077.1

    Status: VALIDATED

    Source sequence(s)
    AL596331
    Consensus CDS
    CCDS25548.1
    UniProtKB/Swiss-Prot
    Q61084
    UniProtKB/TrEMBL
    Q3UVM5
    Related
    ENSMUSP00000002044.10, ENSMUST00000002044.10
    Conserved Domains (3) summary
    cd06405
    Location:45 → 123
    PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
    smart00220
    Location:362 → 621
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd06625
    Location:361 → 621
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

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_000077.7 Reference GRCm39 C57BL/6J

    Range
    105975358..106047482
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_036156711.1 → XP_036012604.1  mitogen-activated protein kinase kinase kinase 3 isoform X2

    UniProtKB/TrEMBL
    Q3UVM5
    Conserved Domains (2) summary
    cd06405
    Location:45 → 123
    PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
    cl21453
    Location:361 → 577
    PKc_like; Protein Kinases, catalytic domain

  2. XM_011249037.4 → XP_011247339.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

    UniProtKB/TrEMBL
    Q3UVM5
    Conserved Domains (2) summary
    cd06405
    Location:35 → 113
    PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
    cd06625
    Location:351 → 611
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

  3. XM_036156710.1 → XP_036012603.1  mitogen-activated protein kinase kinase kinase 3 isoform X1

    UniProtKB/TrEMBL
    Q3UVM5
    Conserved Domains (2) summary
    cd06405
    Location:35 → 113
    PB1_Mekk2_3; The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) ...
    cd06625
    Location:351 → 611
    STKc_MEKK3_like; Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases

RNA

  1. XR_004936967.1 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q61084.1 GenPept UniProtKB/Swiss-Prot:Q61084

Gene LinkOut

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