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    Map3k12 mitogen-activated protein kinase kinase kinase 12 [ Mus musculus (house mouse) ]

    Gene ID: 26404, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Map3k12provided by MGI
    Official Full Name
    mitogen-activated protein kinase kinase kinase 12provided by MGI
    Primary source
    MGI:MGI:1346881
    See related
    Ensembl:ENSMUSG00000023050 AllianceGenome:MGI:1346881
    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
    DLK; MUK; Zpk
    Summary
    Enables protein homodimerization activity and protein serine/threonine kinase activity. Involved in JNK cascade; positive regulation of JUN kinase activity; and protein phosphorylation. Acts upstream of or within negative regulation of motor neuron apoptotic process. Located in cytosol; growth cone; and plasma membrane. Is expressed in several structures, including alimentary system; genitourinary system; integumental system; nervous system; and sensory organ. Orthologous to human MAP3K12 (mitogen-activated protein kinase kinase kinase 12). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in cerebellum adult (RPKM 25.4), CNS E18 (RPKM 18.8) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    15 F3; 15 57.63 cM
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 15 NC_000081.7 (102406079..102425311, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 15 NC_000081.6 (102497647..102517004, complement)

    Chromosome 15 - NC_000081.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E1179 Neighboring gene STARR-seq mESC enhancer starr_39843 Neighboring gene STARR-positive B cell enhancer ABC_E8613 Neighboring gene STARR-seq mESC enhancer starr_39845 Neighboring gene proline rich 13 Neighboring gene predicted gene, 36331 Neighboring gene poly(rC) binding protein 2 Neighboring gene TARBP2, RISC loading complex RNA binding subunit Neighboring gene neuropeptide FF-amide peptide precursor Neighboring gene activating transcription factor 7 Neighboring gene STARR-seq mESC enhancer starr_39849 Neighboring gene uncharacterized LOC105246046

    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. High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity. Verschuuren M, et al. Acta Neuropathol Commun, 2019 Jun 4. PMID 31164177, Free PMC Article
    2. Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease. Le Pichon CE, et al. Sci Transl Med, 2017 Aug 16. PMID 28814543
    3. Dual leucine zipper kinase regulates expression of axon guidance genes in mouse neuronal cells. Blondeau A, et al. Neural Dev, 2016 Jul 28. PMID 27468987, Free PMC Article
    4. Distinct functions of the dual leucine zipper kinase depending on its subcellular localization. Wallbach M, et al. Cell Signal, 2016 Apr. PMID 26776303
    5. Cytoskeletal disruption activates the DLK/JNK pathway, which promotes axonal regeneration and mimics a preconditioning injury. Valakh V, et al. Neurobiol Dis, 2015 May. PMID 25726747, Free PMC Article

    See all (77) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MiR-191-5p alleviates microglial cell injury by targeting Map3k12 (mitogen-activated protein kinase kinase kinase 12) to inhibit the MAPK (mitogen-activated protein kinase) signaling pathway in Alzheimer's disease.
      Title: MiR-191-5p alleviates microglial cell injury by targeting Map3k12 (mitogen-activated protein kinase kinase kinase 12) to inhibit the MAPK (mitogen-activated protein kinase) signaling pathway in Alzheimer's disease.
    2. Activation of MAP3K DLK and LZK in Purkinje cells causes rapid and slow degeneration depending on signaling strength.
      Title: Activation of MAP3K DLK and LZK in Purkinje cells causes rapid and slow degeneration depending on signaling strength.
    3. Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.
      Title: Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.
    4. Study shows that dual leucine zipper kinase inhibition preserves neuronal network connectivity.
      Title: High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity.
    5. Using a sensory neuron-conditional DLK knockout mouse model, we show a time course for the dependency of gene expression changes on the DLK pathway after sciatic nerve injury.
      Title: DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury.
    6. DLK is required for mechanical allodynia and microgliosis after nerve injury by controling a transcriptional program in somatosensory neurons regulating the expression of numerous genes implicated in pain pathogenesis, including Csf1.
      Title: Dual leucine zipper kinase is required for mechanical allodynia and microgliosis after nerve injury.
    7. These findings demonstrate that pathological activation of DLK is a conserved mechanism that regulates neurodegeneration.
      Title: Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease.
    8. These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration.
      Title: Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult.
    9. Results provide the first evidence that axon guidance genes are downstream targets of the dual leucine zipper kinase (DLK) signaling pathway, which through their regulation probably modulates neuronal cell development, structure and function.
      Title: Dual leucine zipper kinase regulates expression of axon guidance genes in mouse neuronal cells.
    10. LZK cooperates with DLK to promote retinal ganglion cell death in response to axon injury.
      Title: Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MAP kinase kinase kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein kinase binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine/threonine kinase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in JNK cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of motor neuron apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-serine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in peptidyl-threonine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of DNA-templated transcription ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of ERK1 and ERK2 cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in post-translational protein modification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    located_in axon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in growth cone IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 12
    Names
    MAPK-upstream kinase
    dual leucine zipper bearing kinase
    leucine-zipper protein kinase
    mixed lineage kinase
    zipper (leucine) protein kinase
    NP_001157115.1
    NP_001345773.1
    NP_001398789.1
    NP_001398790.1
    NP_033608.3
    XP_006521076.1
    XP_017172113.1
    XP_017172114.1
    XP_030104450.1
    XP_030104451.1

    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_001163643.2 → NP_001157115.1  mitogen-activated protein kinase kinase kinase 12

      See identical proteins and their annotated locations for NP_001157115.1

      Status: VALIDATED

      Source sequence(s)
      AC137156
      Consensus CDS
      CCDS27885.1
      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
      Related
      ENSMUSP00000133209.2, ENSMUST00000169377.8
      Conserved Domains (1) summary
      cd14059
      Location:164 → 400
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    2. NM_001358844.2 → NP_001345773.1  mitogen-activated protein kinase kinase kinase 12

      Status: VALIDATED

      Source sequence(s)
      AC137156
      Consensus CDS
      CCDS27885.1
      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
      Related
      ENSMUSP00000127629.2, ENSMUST00000171565.8
      Conserved Domains (1) summary
      cd14059
      Location:164 → 400
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    3. NM_001411860.1 → NP_001398789.1  mitogen-activated protein kinase kinase kinase 12

      Status: VALIDATED

      Source sequence(s)
      AC137156
      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

    4. NM_001411861.1 → NP_001398790.1  mitogen-activated protein kinase kinase kinase 12

      Status: VALIDATED

      Source sequence(s)
      AC137156
      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

    5. NM_009582.5 → NP_033608.3  mitogen-activated protein kinase kinase kinase 12

      See identical proteins and their annotated locations for NP_033608.3

      Status: VALIDATED

      Source sequence(s)
      AC137156
      Consensus CDS
      CCDS27885.1
      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
      Related
      ENSMUSP00000023812.3, ENSMUST00000023812.10
      Conserved Domains (1) summary
      cd14059
      Location:164 → 400
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    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_000081.7 Reference GRCm39 C57BL/6J

      Range
      102406079..102425311 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_030248590.2 → XP_030104450.1  mitogen-activated protein kinase kinase kinase 12 isoform X2

    2. XM_017316624.2 → XP_017172113.1  mitogen-activated protein kinase kinase kinase 12 isoform X1

      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
      Conserved Domains (1) summary
      cd14059
      Location:164 → 400
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    3. XM_030248591.2 → XP_030104451.1  mitogen-activated protein kinase kinase kinase 12 isoform X2

    4. XM_017316625.3 → XP_017172114.1  mitogen-activated protein kinase kinase kinase 12 isoform X1

      UniProtKB/Swiss-Prot
      P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
      Conserved Domains (1) summary
      cd14059
      Location:164 → 400
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    5. XM_006521013.4 → XP_006521076.1  mitogen-activated protein kinase kinase kinase 12 isoform X2

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q60700.1 GenPept UniProtKB/Swiss-Prot:Q60700

    Gene LinkOut

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

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