Map3k5 mitogen-activated protein kinase kinase kinase 5 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Map3k5provided by MGI
Official Full Name: mitogen-activated protein kinase kinase kinase 5provided by MGI
Primary source: MGI:MGI:1346876
See related: Ensembl:ENSMUSG00000071369 AllianceGenome:MGI:1346876
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: ASK; ASK1; Mekk5; MAPKKK5; 7420452D20Rik
Summary: Enables MAP kinase kinase kinase activity and protein kinase binding activity. Involved in several processes, including intracellular signal transduction; positive regulation of JNK cascade; and positive regulation of myoblast differentiation. Acts upstream of or within several processes, including cellular response to reactive nitrogen species; intrinsic apoptotic signaling pathway in response to oxidative stress; and positive regulation of MAPK cascade. Predicted to be located in cytoplasm and external side of plasma membrane. Predicted to be part of IRE1-TRAF2-ASK1 complex and protein kinase complex. Is expressed in several structures, including alimentary system; branchial arch; central nervous system; heart; and sensory organ. Human ortholog(s) of this gene implicated in Huntington's disease. Orthologous to human MAP3K5 (mitogen-activated protein kinase kinase kinase 5). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in bladder adult (RPKM 5.2), cortex adult (RPKM 2.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 A3; 10 9.35 cM

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (19809847..20018496)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (19934101..20142750)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

ASK-1 activation exacerbates kidney dysfunction via increment of glomerular permeability and accelerates cellular aging in diabetic kidney disease model mice.
Title: ASK-1 activation exacerbates kidney dysfunction via increment of glomerular permeability and accelerates cellular aging in diabetic kidney disease model mice.
Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging.
Title: Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging.
Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway.
Title: Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway.
ASK1-ER stress pathway-mediated fibrotic-EV release contributes to the interaction of alveolar epithelial cells and lung fibroblasts to promote mechanical ventilation-induced pulmonary fibrosis.
Title: ASK1-ER stress pathway-mediated fibrotic-EV release contributes to the interaction of alveolar epithelial cells and lung fibroblasts to promote mechanical ventilation-induced pulmonary fibrosis.
Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1.
Title: Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1.
Phosphoproteomics identifies pathways underlying the role of receptor-interaction protein kinase 3 in alcohol-associated liver disease and uncovers apoptosis signal-regulating kinase 1 as a target.
Title: Phosphoproteomics identifies pathways underlying the role of receptor-interaction protein kinase 3 in alcohol-associated liver disease and uncovers apoptosis signal-regulating kinase 1 as a target.
N-acetylgalactosaminyltransferase-4 protects against hepatic ischemia/reperfusion injury by blocking apoptosis signal-regulating kinase 1 N-terminal dimerization.
Title: N-acetylgalactosaminyltransferase-4 protects against hepatic ischemia/reperfusion injury by blocking apoptosis signal-regulating kinase 1 N-terminal dimerization.
ASK1 is a novel molecular target for preventing aminoglycoside-induced hair cell death.
Title: ASK1 is a novel molecular target for preventing aminoglycoside-induced hair cell death.
ASK1 signaling regulates phase-specific glial interactions during neuroinflammation.
Title: ASK1 signaling regulates phase-specific glial interactions during neuroinflammation.
Activation of osteoblast ferroptosis via the METTL3/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss.
Title: Activation of osteoblast ferroptosis via the METTL3/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss.

Submit: New GeneRIF Correction See all GeneRIFs (137)

Variation

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Alleles

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

Endonuclease-mediated (2)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Map3k5 (e-PCR), detects polymorphism
- UniSTS:507048

AB006787 (e-PCR)
- UniSTS:159957

Map3k5 (e-PCR), detects polymorphism
- UniSTS:502773

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables JUN kinase kinase kinase activity	IEA Inferred from Electronic Annotation 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 identical protein binding	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein phosphatase binding	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 JNK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in JNK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amino acid starvation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to reactive nitrogen species	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to oxidative stress	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron intrinsic apoptotic signaling pathway in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in neuron intrinsic apoptotic signaling pathway in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in p38MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in p38MAPK cascade	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of DNA-templated transcription	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 JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JUN kinase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardiac muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of p38MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of p38MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular associated smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular associated smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within programmed necrotic cell death	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of programmed cell death	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of IRE1-TRAF2-ASK1 complex	IEA Inferred from Electronic Annotation more info
part_of IRE1-TRAF2-ASK1 complex	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein kinase complex	IEA Inferred from Electronic Annotation more info
part_of protein kinase complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 5

Names: ASK-1; MAPK/ERK kinase kinase 5; MEK kinase 5; MEKK 5; apoptosis signal-regulating kinase 1

NP_032606.4

EC 2.7.11.25

XP_006512802.1

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_008580.4 → NP_032606.4 mitogen-activated protein kinase kinase kinase 5

See identical proteins and their annotated locations for NP_032606.4

Status: VALIDATED

Source sequence(s)

AC158620, AC158621, AC171277, AK078668, BC133697

Consensus CDS

CCDS35857.1

UniProtKB/Swiss-Prot

O35099, Q14AY5

UniProtKB/TrEMBL

E9PWG9

Related

ENSMUSP00000093485.4, ENSMUST00000095806.10

Conserved Domains (3) summary

smart00220
Location:692 → 945

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06624
Location:678 → 945

STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase

pfam13281
Location:172 → 551

DUF4071; Domain of unknown function (DUF4071)

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_000076.7 Reference GRCm39 C57BL/6J

Range

19809847..20018496

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006512739.5 → XP_006512802.1 mitogen-activated protein kinase kinase kinase 5 isoform X1

Conserved Domains (2) summary

cd06624
Location:678 → 945

STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase

pfam13281
Location:172 → 552

DUF4071; Domain of unknown function (DUF4071)