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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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