Map2k4 mitogen-activated protein kinase kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Map2k4provided by MGI
Official Full Name: mitogen-activated protein kinase kinase 4provided by MGI
Primary source: MGI:MGI:1346869
See related: Ensembl:ENSMUSG00000033352 AllianceGenome:MGI:1346869
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: MEK4; MKK4; Sek1; JNKK1; Serk1; PRKMK4; MAPKK 4
Summary: Predicted to enable JUN kinase kinase activity and molecular adaptor activity. Involved in intrinsic apoptotic signaling pathway in response to hydrogen peroxide and smooth muscle cell apoptotic process. Acts upstream of or within MAPK cascade; negative regulation of motor neuron apoptotic process; and response to wounding. Predicted to be located in axon; dendrite cytoplasm; and perikaryon. Is expressed in several structures, including alimentary system; central nervous system; early conceptus; genitourinary system; and sensory organ. Human ortholog(s) of this gene implicated in colorectal cancer; ovarian serous carcinoma; pancreatic cancer; respiratory system cancer (multiple); and urinary bladder cancer. Orthologous to human MAP2K4 (mitogen-activated protein kinase kinase 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in cerebellum adult (RPKM 19.2), cortex adult (RPKM 18.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 B3; 11 40.53 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (65579070..65679185, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (65688244..65788359, complement)

Chromosome 11 - NC_000077.7 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 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?

Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells.
Title: Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells.
The role of MKK4 in T-cell development and immunity to viral infections.
Title: The role of MKK4 in T-cell development and immunity to viral infections.
Astrocyte-Derived Exosomal microRNA miR-200a-3p Prevents MPP(+)-Induced Apoptotic Cell Death Through Down-Regulation of MKK4.
Title: Astrocyte-Derived Exosomal microRNA miR-200a-3p Prevents MPP(+)-Induced Apoptotic Cell Death Through Down-Regulation of MKK4.
These results suggest that MKK4 and MKK7 may serve redundant and unique roles in molecular signaling important for retinal development and injury response following axonal insult.
Title: Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.
MKK4 is the major MAP2K, which activates JNK in acute liver injury. p38, the other downstream target of MKK4, does not contribute to liver injury from APAP or TNF/galactosamine.
Title: The role of MAP2 kinases and p38 kinase in acute murine liver injury models.
MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing.
Title: MKK4 activates non-canonical NFκB signaling by promoting NFκB2-p100 processing.
Demonstrate that Mkk4 is a negative regulator of the TGF-beta1 signaling associated with atrial remodeling and arrhythmogenesis with age.
Title: Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.
This study provides compelling evidence for the pivotal roles of the ZPK/DLK and MKK4/MAP2K4-dependent mechanism in axotomy-induced motoneuron death in neonates.
Title: ZPK/DLK and MKK4 form the critical gateway to axotomy-induced motoneuron death in neonates.
The loss of mkk4 and mkk7 locks damaged exocrine cells in a permanently de-differentiated state.
Title: Impaired JNK signaling cooperates with KrasG12D expression to accelerate pancreatic ductal adenocarcinoma.
Studies identify the dual-specific kinase MKK4 as a master regulator of liver regeneration. MKK4 silencing robustly increased the regenerative capacity of hepatocytes in mouse models of liver regeneration and acute and chronic liver failure.
Title: A Direct in vivo RNAi screen identifies MKK4 as a key regulator of liver regeneration.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Variation

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Alleles

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

Endonuclease-mediated (3)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

9_15_91.seq (e-PCR)
- UniSTS:124712

Map2k4 (e-PCR), detects polymorphism
- UniSTS:527411

C86896 (e-PCR)
- UniSTS:208694

RH70575 (e-PCR)
- UniSTS:74809

RH12704 (e-PCR)
- UniSTS:43438

NoName (e-PCR)
- UniSTS:225260

U18310 (e-PCR)
- UniSTS:125686

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables JUN kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables molecular adaptor activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within JNK cascade	ISO Inferred from Sequence Orthology more info	PubMed
involved_in JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within MAPK cascade	IPI Inferred from Physical Interaction more info	PubMed
involved_in cell growth involved in cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in cell growth involved in cardiac muscle cell development	ISO Inferred from Sequence Orthology more info
involved_in cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to sorbitol	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway in response to hydrogen peroxide	IDA Inferred from Direct Assay 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 positive regulation of DNA replication	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA replication	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of JUN kinase activity	ISO Inferred from Sequence Orthology more info	PubMed
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of nitric-oxide synthase biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of nitric-oxide synthase biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to wounding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smooth muscle cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite cytoplasm	IEA Inferred from Electronic Annotation more info
located_in dendrite cytoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 4

Names: C-JUN N-terminal kinase kinase 1; JNK kinase 1; JNK-activating kinase 1; MAP kinase kinase 4; MAPK/ERK kinase 4; SAPK/ERK kinase 1; SAPK/Erk/kinase 1

NP_001303296.1

EC 2.7.12.2

NP_001303297.1

EC 2.7.12.2

NP_001303298.1

EC 2.7.12.2

NP_001349668.1

EC 2.7.12.2

NP_001349669.1

EC 2.7.12.2

NP_033183.1

EC 2.7.12.2

XP_011247335.1

EC 2.7.12.2

XP_030101878.1

EC 2.7.12.2

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_001316367.1 → NP_001303296.1 dual specificity mitogen-activated protein kinase kinase 4 isoform a

Status: VALIDATED

Source sequence(s)

AK036928, AK139777, AL662895, BY277234

UniProtKB/TrEMBL

Q543X6

Conserved Domains (1) summary

cd06616
Location:104 → 394

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4
NM_001316368.1 → NP_001303297.1 dual specificity mitogen-activated protein kinase kinase 4 isoform c

Status: VALIDATED

Source sequence(s)

AK036928, AL662895, BY244326, BY277234

UniProtKB/TrEMBL

Q543X6

Conserved Domains (1) summary

cl21453
Location:1 → 239

PKc_like; Protein Kinases, catalytic domain
NM_001316369.1 → NP_001303298.1 dual specificity mitogen-activated protein kinase kinase 4 isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks two alternate 5' exons compared to variant 1, that causes translation initiation from a downstream AUG. The resulting isoform (c) is shorter at the N-terminus compared to isoform a. Variants 3 and 4 both encode the same isoform (c).

Source sequence(s)

AK036928, AL662895, BY277234, CB723868

UniProtKB/TrEMBL

Q543X6

Conserved Domains (1) summary

cl21453
Location:1 → 239

PKc_like; Protein Kinases, catalytic domain
NM_001362739.1 → NP_001349668.1 dual specificity mitogen-activated protein kinase kinase 4 isoform d

Status: VALIDATED

Source sequence(s)

AL662895, AL663069

UniProtKB/TrEMBL

Q8K2U0

Conserved Domains (1) summary

cd06616
Location:1 → 267

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4
NM_001362740.1 → NP_001349669.1 dual specificity mitogen-activated protein kinase kinase 4 isoform d

Status: VALIDATED

Source sequence(s)

AL662895, AL663069

UniProtKB/TrEMBL

Q8K2U0

Conserved Domains (1) summary

cd06616
Location:1 → 267

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4
NM_009157.5 → NP_033183.1 dual specificity mitogen-activated protein kinase kinase 4 isoform b

See identical proteins and their annotated locations for NP_033183.1

Status: VALIDATED

Source sequence(s)

AK036928, AL662895, BY277234

Consensus CDS

CCDS24844.1

UniProtKB/Swiss-Prot

P47809

UniProtKB/TrEMBL

Q543X6

Related

ENSMUSP00000041282.4, ENSMUST00000046963.10

Conserved Domains (1) summary

cd06616
Location:93 → 383

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4

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_000077.7 Reference GRCm39 C57BL/6J

Range

65579070..65679185 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030246018.1 → XP_030101878.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X1

UniProtKB/TrEMBL

Q8K2U0

Conserved Domains (1) summary

cd06616
Location:1 → 267

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4
XM_011249033.3 → XP_011247335.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X1

See identical proteins and their annotated locations for XP_011247335.1

UniProtKB/TrEMBL

Q8K2U0

Conserved Domains (1) summary

cd06616
Location:1 → 267

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4