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Map3k20 mitogen-activated protein kinase kinase kinase 20 [ Mus musculus (house mouse) ]

Gene ID: 65964, updated on 21-Apr-2024

Summary

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Official Symbol
Map3k20provided by MGI
Official Full Name
mitogen-activated protein kinase kinase kinase 20provided by MGI
Primary source
MGI:MGI:2443258
See related
Ensembl:ENSMUSG00000004085 AllianceGenome:MGI:2443258
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
MRK; Zak; MLTK; HCCS-4; MLTKbeta; MLTKalpha; B230120H23Rik
Summary
Enables ATP binding activity; MAP kinase kinase kinase activity; and magnesium ion binding activity. Involved in intracellular signal transduction; limb development; and protein phosphorylation. Acts upstream of or within cytoskeleton organization and embryonic digit morphogenesis. Located in cytoplasm and nucleus. Is expressed in heart; limb; limb bud; and urinary system. Used to study split hand-foot malformation. Human ortholog(s) of this gene implicated in centronuclear myopathy 6 with fiber-type disproportion. Orthologous to human MAP3K20 (mitogen-activated protein kinase kinase kinase 20). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in heart adult (RPKM 20.9), bladder adult (RPKM 15.7) and 20 other tissues See more
Orthologs
human all
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Genomic context

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Location:
2 C3; 2 43.11 cM
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 2 NC_000068.8 (72115970..72272954)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 2 NC_000068.7 (72285637..72442610)

Chromosome 2 - NC_000068.8Genomic Context describing neighboring genes Neighboring gene Rap guanine nucleotide exchange factor (GEF) 4 Neighboring gene STARR-seq mESC enhancer starr_04813 Neighboring gene predicted gene, 26408 Neighboring gene predicted gene, 52555 Neighboring gene STARR-positive B cell enhancer mm9_chr2:71987118-71987419 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:71995766-71995967 Neighboring gene STARR-seq mESC enhancer starr_04815 Neighboring gene predicted gene, 52556 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:72234732-72234933 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:72235096-72235279 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:72237569-72237890 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:72239438-72239655 Neighboring gene STARR-seq mESC enhancer starr_04817 Neighboring gene STARR-positive B cell enhancer ABC_E9198 Neighboring gene predicted gene, 39847 Neighboring gene cell division cycle associated 7

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. ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle. Nordgaard C, et al. EMBO J, 2022 Sep 1. PMID 35899396, Free PMC Article
  2. A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response. Jandhyala DM, et al. Toxins (Basel), 2016 Sep 2. PMID 27598200, Free PMC Article
  3. Sequence changes at the V-D junction of the VH1 heavy chain of anti-phosphocholine antibodies alter binding to and protection against Streptococcus pneumoniae. Guo WX, et al. Int Immunol, 1997 May. PMID 9184912
  4. Targeted inhibition of ZAK ameliorates renal interstitial fibrosis. Shu S, et al. Transl Res, 2022 Aug. PMID 35276386
  5. Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and mixed lineage kinase 7 small interfering RNA. Wang X, et al. J Biol Chem, 2005 May 13. PMID 15737997

See all (28) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Myofibrillar myopathy hallmarks associated with ZAK deficiency.
    Title: Myofibrillar myopathy hallmarks associated with ZAK deficiency.
  2. ZAKbeta is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle.
    Title: ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle.
  3. Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
    Title: Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
  4. Zak-/- mice demonstrate a distinct ribotoxic stress-associated phenotype in response to ricin.
    Title: A Novel Zak Knockout Mouse with a Defective Ribotoxic Stress Response.
  5. ZAK is a key player in mammalian limb patterning in humans and mice.
    Title: Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice.
  6. Exome sequencing analysis between SM/J and A/J mice identified 4 genes (Itga6, Zak, Gpr155, and Mtx2) with nonsynonymous coding SNPs. These four genes might be candidate genes for type 2 diabetes caused by gene-gene interactions.
    Title: Searching for genomic region of high-fat diet-induced type 2 diabetes in mouse chromosome 2 by analysis of congenic strains.
  7. Results show that mixed lineage kinase-like mitogen-activated protein triple kinase (MLTK_-alpha plays a key role in the UVB- and EGF-induced phosphorylation of histone H3 at Ser28.
    Title: Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha.
  8. PKNalpha functions as not only an upstream activator of MLTKalpha but also a putative scaffold protein for the p38gamma MAPK signaling pathway
    Title: Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN.
  9. Mixed lineage kinase 7 (MLK7), a splice variant of the human ZAK gene (ortholog of mouse B230120H23Rik), encodes an isoform which is the MAPKKK required for modulation of the stress-activated MAPKs downstream of anisomycin and UV stimulation.
    Title: Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and mixed lineage kinase 7 small interfering RNA.
Submit: New GeneRIF Correction

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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables ATP binding ISO
Inferred from Sequence Orthology
more info
  
enables JUN kinase kinase kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables MAP kinase kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables MAP kinase kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables RNA binding IEA
Inferred from Electronic Annotation
more info
  
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding ISO
Inferred from Sequence Orthology
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 kinase activator activity ISO
Inferred from Sequence Orthology
more info
  
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables rRNA binding IEA
Inferred from Electronic Annotation
more info
  
enables ribosome binding ISO
Inferred from Sequence Orthology
more info
  
enables small ribosomal subunit rRNA binding ISO
Inferred from Sequence Orthology
more info
  
enables stalled ribosome sensor activity ISO
Inferred from Sequence Orthology
more info
  
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in DNA damage checkpoint signaling ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of GCN2-mediated signaling ISO
Inferred from Sequence Orthology
more info
  
involved_in JNK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in JNK cascade ISO
Inferred from Sequence Orthology
more info
  
involved_in MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to UV-B ISO
Inferred from Sequence Orthology
more info
  
involved_in cellular response to gamma radiation ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within cytoskeleton organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in embryonic digit morphogenesis ISO
Inferred from Sequence Orthology
more info
  
involved_in inflammatory response ISO
Inferred from Sequence Orthology
more info
  
involved_in intracellular signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in limb development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in limb development ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of stress-activated protein kinase signaling cascade ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of translation in response to endoplasmic reticulum stress ISO
Inferred from Sequence Orthology
more info
  
involved_in p38MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in p38MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of apoptotic process ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of mitotic DNA damage checkpoint ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of positive regulation of programmed cell death ISO
Inferred from Sequence Orthology
more info
  
involved_in protein autophosphorylation ISO
Inferred from Sequence Orthology
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_positive_effect pyroptosis ISO
Inferred from Sequence Orthology
more info
  
involved_in stress-activated MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in stress-activated MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
involved_in stress-activated protein kinase signaling cascade ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 20
Names
MLK-like mitogen-activated protein triple kinase
MLK-related kinase
human cervical cancer suppressor gene 4 protein
leucine zipper- and sterile alpha motif kinase ZAK
leucine zipper- and sterile alpha motif-containing kinase
mitogen-activated protein kinase kinase kinase MLT
mixed lineage kinase-related kinase
sterile alpha motif and leucine zipper containing kinase AZK
NP_001158263.1
NP_075544.1
NP_835185.2
XP_006500060.1
XP_006500061.1
XP_030107797.1

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_001164791.2 → NP_001158263.1  mitogen-activated protein kinase kinase kinase 20 isoform 3

    See identical proteins and their annotated locations for NP_001158263.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks several 3' exon but has an alternate 3' exon, as compared to variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus, as compared to isoform 1.
    Source sequence(s)
    AL928699
    Consensus CDS
    CCDS50605.1
    UniProtKB/TrEMBL
    Q3TRG2
    Related
    ENSMUSP00000118983.2, ENSMUST00000135469.8
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  2. NM_023057.6 → NP_075544.1  mitogen-activated protein kinase kinase kinase 20 isoform 1

    See identical proteins and their annotated locations for NP_075544.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) is the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL845274, AL928699
    Consensus CDS
    CCDS38143.1
    UniProtKB/Swiss-Prot
    Q3V1X8, Q8BR73, Q9ESL3, Q9ESL4
    Related
    ENSMUSP00000088334.6, ENSMUST00000090824.12
    Conserved Domains (2) summary
    cd09529
    Location:338 → 408
    SAM_MLTK; SAM domain of MLTK subfamily
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  3. NM_178084.5 → NP_835185.2  mitogen-activated protein kinase kinase kinase 20 isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks multiple 3' exon but has an alternate 3' segment, as compared to variant 1. The resulting isoform (2) is much shorter and has a distinct C-terminus, as compared to isoform 1.
    Source sequence(s)
    AL928699
    UniProtKB/Swiss-Prot
    Q9ESL4
    Related
    ENSMUST00000150126.8
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

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_000068.8 Reference GRCm39 C57BL/6J

    Range
    72115970..72272954
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006499997.4 → XP_006500060.1  mitogen-activated protein kinase kinase kinase 20 isoform X1

    See identical proteins and their annotated locations for XP_006500060.1

    UniProtKB/Swiss-Prot
    Q3V1X8, Q8BR73, Q9ESL3, Q9ESL4
    Conserved Domains (2) summary
    cd09529
    Location:338 → 408
    SAM_MLTK; SAM domain of MLTK subfamily
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  2. XM_030251937.2 → XP_030107797.1  mitogen-activated protein kinase kinase kinase 20 isoform X3

    UniProtKB/TrEMBL
    Q3TRG2
    Conserved Domains (1) summary
    cd14060
    Location:22 → 263
    STKc_MLTK; Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase

  3. XM_006499998.4 → XP_006500061.1  mitogen-activated protein kinase kinase kinase 20 isoform X2

    Conserved Domains (2) summary
    cd09529
    Location:22 → 92
    SAM_MLTK; SAM domain of MLTK subfamily
    PTZ00112
    Location:292 → 411
    PTZ00112; origin recognition complex 1 protein; Provisional

RNA

  1. XR_004940679.1 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9ESL4.1 GenPept UniProtKB/Swiss-Prot:Q9ESL4

Gene LinkOut

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