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

Summary

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 MAPK cascade; embryonic digit morphogenesis; and protein phosphorylation. Acts upstream of or within cytoskeleton organization. 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, Nov 2024]
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

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_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Myofibrillar myopathy hallmarks associated with ZAK deficiency.
Title: Myofibrillar myopathy hallmarks associated with ZAK deficiency.
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.
Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
Title: Targeted inhibition of ZAK ameliorates renal interstitial fibrosis.
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.
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.
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.
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.
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.
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.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (5) 1 citation
Gene trapped (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AV006891 (e-PCR)
- UniSTS:165174

G36384 (e-PCR)
- UniSTS:33089

RH80553 (e-PCR)
- UniSTS:88774

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 JUN kinase kinase kinase activity	ISS Inferred from Sequence or Structural Similarity 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 magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables protein kinase activator activity	ISO Inferred from Sequence Orthology more info
enables protein kinase activator activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine 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 ribosome binding	ISO Inferred from Sequence Orthology more info
enables ribosome binding	ISS Inferred from Sequence or Structural Similarity more info
enables small ribosomal subunit rRNA binding	ISO Inferred from Sequence Orthology more info
enables small ribosomal subunit rRNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables stalled ribosome sensor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
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
acts_upstream_of GCN2-mediated signaling	ISS Inferred from Sequence or Structural Similarity 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
involved_in cellular response to UV-B	ISO Inferred from Sequence Orthology more info
involved_in cellular response to UV-B	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to gamma radiation	IEA Inferred from Electronic Annotation 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic digit morphogenesis	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
involved_in p38MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of mitotic DNA damage checkpoint	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of mitotic DNA damage checkpoint	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of positive regulation of programmed cell death	ISO Inferred from Sequence Orthology more info
acts_upstream_of positive regulation of programmed cell death	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity 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 pyroptotic inflammatory response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_positive_effect pyroptotic inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor 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	IEA Inferred from Electronic Annotation 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

EC 2.7.11.25

NP_075544.1

EC 2.7.11.25

NP_835185.2

EC 2.7.11.25

XP_006500060.1

EC 2.7.11.25

XP_006500061.1

EC 2.7.11.25

XP_030107797.1

EC 2.7.11.25

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)

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
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
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

NC_000068.8 Reference GRCm39 C57BL/6J

Range

72115970..72272954

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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