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    Map3k8 mitogen-activated protein kinase kinase kinase 8 [ Mus musculus (house mouse) ]

    Gene ID: 26410, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Map3k8provided by MGI
    Official Full Name
    mitogen-activated protein kinase kinase kinase 8provided by MGI
    Primary source
    MGI:MGI:1346878
    See related
    Ensembl:ENSMUSG00000024235 AllianceGenome:MGI:1346878
    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
    Cot; Est; Estf; Tpl2; Tpl-2; c-COT; Cot/Tpl2
    Summary
    Predicted to enable MAP kinase kinase kinase activity. Predicted to be involved in MAPK cascade and gap junction-mediated intercellular transport. Predicted to be located in cytosol. Is expressed in several structures, including adipose tissue; adrenal gland; alimentary system; hemolymphoid system gland; and reproductive system. Human ortholog(s) of this gene implicated in clear cell renal cell carcinoma; lung cancer; and stomach cancer. Orthologous to human MAP3K8 (mitogen-activated protein kinase kinase kinase 8). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in spleen adult (RPKM 3.1), lung adult (RPKM 2.9) and 27 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Map3k8 in Genome Data Viewer
    Location:
    18 A1; 18 2.73 cM
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 18 NC_000084.7 (4331325..4352978, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 18 NC_000084.6 (4331325..4352953, complement)

    Chromosome 18 - NC_000084.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_43673 Neighboring gene predicted gene, 41657 Neighboring gene STARR-seq mESC enhancer starr_43674 Neighboring gene STARR-positive B cell enhancer ABC_E7569 Neighboring gene CapStarr-seq enhancer MGSCv37_chr18:4295908-4296095 Neighboring gene carbohydrate sulfotransferase 10 pseudogene Neighboring gene STARR-seq mESC enhancer starr_43675 Neighboring gene RIKEN cDNA 4833419F23 gene Neighboring gene CapStarr-seq enhancer MGSCv37_chr18:4375540-4375727 Neighboring gene mitochondrial poly(A) polymerase

    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. Genetic and pharmacological targeting of TPL-2 kinase ameliorates experimental colitis: a potential target for the treatment of Crohn's disease? Lawrenz M, et al. Mucosal Immunol, 2012 Mar. PMID 22157885
    2. Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis. Sánchez Á, et al. Sci Rep, 2017 Jul 10. PMID 28694430, Free PMC Article
    3. Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing. Acuff NV, et al. J Leukoc Biol, 2017 Jun. PMID 28356348, Free PMC Article
    4. Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production. Mielke LA, et al. J Immunol, 2009 Dec 15. PMID 19933865, Free PMC Article
    5. Ablation of tumor progression locus 2 promotes a type 2 Th cell response in Ovalbumin-immunized mice. Watford WT, et al. J Immunol, 2010 Jan 1. PMID 19955521, Free PMC Article

    See all (143) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice.
      Title: TPL2 kinase activity regulates microglial inflammatory responses and promotes neurodegeneration in tauopathy mice.
    2. Tumor Progression Locus 2 Protects against Acute Respiratory Distress Syndrome in Influenza A Virus-Infected Mice.
      Title: Tumor Progression Locus 2 Protects against Acute Respiratory Distress Syndrome in Influenza A Virus-Infected Mice.
    3. Loss of Tpl2 activates compensatory signaling and resistance to EGFR/MET dual inhibition in v-RAS transduced keratinocytes.
      Title: Loss of Tpl2 activates compensatory signaling and resistance to EGFR/MET dual inhibition in v-RAS transduced keratinocytes.
    4. TPL-2 Inhibits IFN-beta Expression via an ERK1/2-TCF-FOS Axis in TLR4-Stimulated Macrophages.
      Title: TPL-2 Inhibits IFN-β Expression via an ERK1/2-TCF-FOS Axis in TLR4-Stimulated Macrophages.
    5. Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.
      Title: Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.
    6. Tpl2 Ablation Leads to Hypercytokinemia and Excessive Cellular Infiltration to the Lungs During Late Stages of Influenza Infection.
      Title: Tpl2 Ablation Leads to Hypercytokinemia and Excessive Cellular Infiltration to the Lungs During Late Stages of Influenza Infection.
    7. Toll-Like Receptor 2-Tpl2-Dependent ERK Signaling Drives Inverse Interleukin 12 Regulation in Dendritic Cells and Macrophages.
      Title: Toll-Like Receptor 2-Tpl2-Dependent ERK Signaling Drives Inverse Interleukin 12 Regulation in Dendritic Cells and Macrophages.
    8. Tpl2 kinase regulates inflammation but not tumorigenesis in mice.
      Title: Tpl2 kinase regulates inflammation but not tumorigenesis in mice.
    9. Tpl2 Protects Against Fulminant Hepatitis Through Mobilization of Myeloid-Derived Suppressor Cells.
      Title: Tpl2 Protects Against Fulminant Hepatitis Through Mobilization of Myeloid-Derived Suppressor Cells.
    10. promotes both liver and systemic metabolic disturbances by specifically increasing MKK7-JNK activation
      Title: Tumor Progression Locus 2 in Hepatocytes Potentiates Both Liver and Systemic Metabolic Disorders in Mice.
    Submit: New GeneRIF Correction See all GeneRIFs (86)

    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 JUN kinase kinase kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase kinase kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables magnesium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gap junction-mediated intercellular transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in immune system process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of inflammatory response IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 8
    Names
    COT proto-oncogene serine/threonine-protein kinase
    cancer Osaka thyroid oncogene
    proto-oncogene c-Cot
    serine/threonine-protein kinase cot
    tumor progression locus 2
    NP_031772.1
    XP_006526007.1
    XP_036017050.1
    XP_036017051.1

    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_007746.2 → NP_031772.1  mitogen-activated protein kinase kinase kinase 8

      See identical proteins and their annotated locations for NP_031772.1

      Status: VALIDATED

      Source sequence(s)
      AC138768
      Consensus CDS
      CCDS29036.1
      UniProtKB/Swiss-Prot
      Q07174
      UniProtKB/TrEMBL
      Q3U086, Q3UEB8
      Related
      ENSMUSP00000025078.3, ENSMUST00000025078.10
      Conserved Domains (2) summary
      smart00220
      Location:146 → 386
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd13995
      Location:133 → 388
      STKc_MAP3K8; Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8

    RNA

    1. NR_157375.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AK140334, AK171403
      Related
      ENSMUST00000173930.8

    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_000084.7 Reference GRCm39 C57BL/6J

      Range
      4331325..4352978 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036161157.1 → XP_036017050.1  mitogen-activated protein kinase kinase kinase 8 isoform X2

      Conserved Domains (1) summary
      cl21453
      Location:80 → 211
      PKc_like; Protein Kinases, catalytic domain

    2. XM_006525944.3 → XP_006526007.1  mitogen-activated protein kinase kinase kinase 8 isoform X1

      Conserved Domains (1) summary
      cl21453
      Location:2 → 231
      PKc_like; Protein Kinases, catalytic domain

    3. XM_036161158.1 → XP_036017051.1  mitogen-activated protein kinase kinase kinase 8 isoform X3

      Conserved Domains (1) summary
      cl21453
      Location:65 → 196
      PKc_like; Protein Kinases, catalytic domain

    RNA

    1. XR_003952522.2 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q07174.1 GenPept UniProtKB/Swiss-Prot:Q07174

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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