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

Gene ID: 26398, updated on 27-Nov-2024

Summary

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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

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See Map2k4 in Genome Data Viewer
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_000077.7Genomic Context describing neighboring genes Neighboring gene VISTA enhancer mm85 Neighboring gene predicted gene, 26128 Neighboring gene predicted gene, 30786 Neighboring gene predicted gene, 40026 Neighboring gene STARR-seq mESC enhancer starr_29772 Neighboring gene microRNA 744 Neighboring gene predicted gene, 53682 Neighboring gene zinc finger with KRAB and SCAN domains 6 Neighboring gene dynein, axonemal, heavy chain 9 Neighboring gene STARR-seq mESC enhancer starr_29773 Neighboring gene STARR-seq mESC enhancer starr_29774 Neighboring gene predicted gene, 40027

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. Targeted deletion of MKK4 gene potentiates TNF-induced apoptosis through the down-regulation of NF-kappa B activation and NF-kappa B-regulated antiapoptotic gene products. Sethi G, et al. J Immunol, 2007 Aug 1. PMID 17641059
  2. The role of MKK4 in T-cell development and immunity to viral infections. Preston SP, et al. Immunol Cell Biol, 2021 Apr. PMID 33175451, Free PMC Article
  3. Disruption of MKK4 signaling reveals its tumor-suppressor role in embryonic stem cells. Cazillis M, et al. Oncogene, 2004 Jun 10. PMID 15122334
  4. SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development. Swat W, et al. Immunity, 1998 May. PMID 9620683
  5. Dynamic expression of SEK1 suggests multiple roles of the gene during embryogenesis and in adult brain of mice. Lee JK, et al. Brain Res Mol Brain Res, 1999 Mar 20. PMID 10095085

See all (109) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing.
    Title: MKK4 activates non-canonical NFκB signaling by promoting NFκB2-p100 processing.
  7. 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.
  8. 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.
  9. 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.
  10. 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

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 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 IBA
Inferred from Biological aspect of Ancestor
more info
  
enables MAP kinase kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables histone H2AXY142 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3Y41 kinase activity IEA
Inferred from Electronic Annotation
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
  
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 chromatin remodeling 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 protein phosphorylation ISO
Inferred from Sequence Orthology
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
NP_001303297.1
NP_001303298.1
NP_001349668.1
NP_001349669.1
NP_033183.1
XP_011247335.1
XP_030101878.1

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_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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  1. NC_000077.7 Reference GRCm39 C57BL/6J

    Range
    65579070..65679185 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P47809.2 GenPept UniProtKB/Swiss-Prot:P47809

Gene LinkOut

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