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Map2k4 mitogen activated protein kinase kinase 4 [ Rattus norvegicus (Norway rat) ]

Gene ID: 287398, updated on 14-Nov-2024

Summary

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Official Symbol
Map2k4provided by RGD
Official Full Name
mitogen activated protein kinase kinase 4provided by RGD
Primary source
RGD:1307040
See related
EnsemblRapid:ENSRNOG00000003834 AllianceGenome:RGD:1307040
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Rattus norvegicus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as
MKK4; Sek1
Summary
Enables JUN kinase kinase activity. Involved in several processes, including cellular response to sorbitol; positive regulation of JNK cascade; and positive regulation of macromolecule metabolic process. Located in axon; dendrite cytoplasm; and perikaryon. Used to study transient cerebral ischemia. 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
Biased expression in Brain (RPKM 321.5), Muscle (RPKM 175.2) and 9 other tissues See more
Orthologs
human mouse all
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Genomic context

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See Map2k4 in Genome Data Viewer
Location:
10q24
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCr8 (GCF_036323735.1) 10 NC_086028.1 (50842348..50947063, complement)
RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 10 NC_051345.1 (50343227..50447956, complement)
106 previous assembly Rnor_6.0 (GCF_000001895.5) 10 NC_005109.4 (52196121..52301887, complement)

Chromosome 10 - NC_086028.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC120095121 Neighboring gene myocardin Neighboring gene uncharacterized LOC102554159 Neighboring gene THAP domain-containing protein 5-like Neighboring gene zinc finger protein 18 Neighboring gene dynein, axonemal, heavy chain 9 Neighboring gene uncharacterized LOC120095122

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
  • Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
  • BioProject: PRJNA238328
  • Publication: PMID 24510058
  • Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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Related articles in PubMed

  1. The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill. Rui T, et al. Front Oncol, 2020. PMID 32850377, Free PMC Article
  2. Evidence for multiple activators for stress-activated protein kinase/c-Jun amino-terminal kinases. Existence of novel activators. Moriguchi T, et al. J Biol Chem, 1995 Jun 2. PMID 7768885
  3. Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte hypertrophy. Choukroun G, et al. J Clin Invest, 1998 Oct 1. PMID 9769323, Free PMC Article
  4. Human gastric cancer kinase profile and prognostic significance of MKK4 kinase. Wu CW, et al. Am J Pathol, 2000 Jun. PMID 10854223, Free PMC Article
  5. High-density single nucleotide polymorphism array defines novel stage and location-dependent allelic imbalances in human bladder tumors. Koed K, et al. Cancer Res, 2005 Jan 1. PMID 15665277

See all (58) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MKK4 Knockdown Plays a Protective Role in Hemorrhagic Shock-Induced Liver Injury through the JNK Pathway.
    Title: MKK4 Knockdown Plays a Protective Role in Hemorrhagic Shock-Induced Liver Injury through the JNK Pathway.
  2. Findings indicated that miR-27a-3p inhibitor protected against epilepsy-induced inflammatory response and hippocampal neuronal apoptosis by targeting MAP2K4.
    Title: MicroRNA-27a-3p Downregulation Inhibits Inflammatory Response and Hippocampal Neuronal Cell Apoptosis by Upregulating Mitogen-Activated Protein Kinase 4 (MAP2K4) Expression in Epilepsy: In Vivo and In Vitro Studies.
  3. MKK4 overexpression enhanced TNF-alpha-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation.
    Title: MicroRNA-145 attenuates TNF-α-driven cartilage matrix degradation in osteoarthritis via direct suppression of MKK4.
  4. 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.
  5. These data support a model in which MKK4 activation at the metastatic site causes a cell-cycle arrest.
    Title: MKK4 suppresses metastatic colonization by multiple highly metastatic prostate cancer cell lines through a transient impairment in cell cycle progression.
  6. SGK1 negatively regulates stress-activated signaling through inhibition of SEK1 function.
    Title: Negative regulation of SEK1 signaling by serum- and glucocorticoid-inducible protein kinase 1.
  7. Mitogen-activated protein kinase kinase 4 deficiency in cardiomyocytes causes connexin 43 reduction and couples hypertrophic signals to ventricular arrhythmogenesis.
    Title: Mitogen-activated protein kinase kinase 4 deficiency in cardiomyocytes causes connexin 43 reduction and couples hypertrophic signals to ventricular arrhythmogenesis.
  8. enzyme inhibition by cocoa-derived procyanidins protects from neuronal apoptosis
    Title: Cocoa procyanidins attenuate 4-hydroxynonenal-induced apoptosis of PC12 cells by directly inhibiting mitogen-activated protein kinase kinase 4 activity.
  9. Inhibition of the specific kinases (one of which is Map2k4) involved in cell death triggered by Thioredoxin/Thioredoxin reductase -dysfunction could represent a novel and selective therapeutic approach in neurodegenerative disorders.
    Title: Inhibition of thioredoxin reductase induces apoptosis in neuronal cell lines: role of glutathione and the MKK4/JNK pathway.
Submit: New GeneRIF Correction

Pathways from PubChem

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General gene information

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Markers

Homology

Gene Ontology Provided by RGD

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables JUN kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
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/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 IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
involved_in cell growth involved in cardiac muscle cell development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to mechanical stimulus ISO
Inferred from Sequence Orthology
more info
  
involved_in cellular response to sorbitol IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in intrinsic apoptotic signaling pathway in response to hydrogen peroxide ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within negative regulation of motor neuron apoptotic process ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of DNA replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JNK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of neuron apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within response to wounding ISO
Inferred from Sequence Orthology
more info
  
involved_in smooth muscle cell apoptotic process ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
located_in axon IDA
Inferred from Direct Assay
more info
 PubMed 
located_in dendrite cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perikaryon IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
dual specificity mitogen-activated protein kinase kinase 4
Names
MAP2K4delta
SAPK/ERK kinase 1
NP_001025194.1
XP_038941354.1
XP_063124696.1
XP_063124697.1
XP_063124698.1
XP_063124699.1

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_001030023.2 → NP_001025194.1  dual specificity mitogen-activated protein kinase kinase 4

    See identical proteins and their annotated locations for NP_001025194.1

    Status: VALIDATED

    Source sequence(s)
    JAXUCZ010000010
    UniProtKB/TrEMBL
    F1LP57, Q4KSH6
    Related
    ENSRNOP00000081371.2, ENSRNOT00000109134.2
    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_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

  1. NC_086028.1 Reference GRCr8

    Range
    50842348..50947063 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_039085426.2 → XP_038941354.1  dual specificity mitogen-activated protein kinase kinase 4 isoform X3

    UniProtKB/TrEMBL
    F1LP57, S4VP54
    Related
    ENSRNOP00000095727.1, ENSRNOT00000112493.2
    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. XM_063268626.1 → XP_063124696.1  dual specificity mitogen-activated protein kinase kinase 4 isoform X1

  3. XM_063268627.1 → XP_063124697.1  dual specificity mitogen-activated protein kinase kinase 4 isoform X2

    Related
    ENSRNOP00000102620.1, ENSRNOT00000141706.1

  4. XM_063268629.1 → XP_063124699.1  dual specificity mitogen-activated protein kinase kinase 4 isoform X5

  5. XM_063268628.1 → XP_063124698.1  dual specificity mitogen-activated protein kinase kinase 4 isoform X4

Nucleotide Protein Strain
Heading Accession and Version

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