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

Summary

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

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_086028.1 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: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.

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General gene information

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Gene Ontology Provided by RGD

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	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
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
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 nitric-oxide synthase biosynthetic 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
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
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

EC 2.7.1.-

EC 2.7.12.2

XP_038941354.1

EC 2.7.1.-

EC 2.7.12.2

XP_063124696.1

EC 2.7.1.-

EC 2.7.12.2

XP_063124697.1

EC 2.7.1.-

EC 2.7.12.2

XP_063124698.1

EC 2.7.1.-

EC 2.7.12.2

XP_063124699.1

EC 2.7.1.-

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_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

NC_086028.1 Reference GRCr8

Range

50842348..50947063 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
XM_063268626.1 → XP_063124696.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X1
XM_063268627.1 → XP_063124697.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X2

Related

ENSRNOP00000102620.1, ENSRNOT00000141706.1
XM_063268629.1 → XP_063124699.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X5
XM_063268628.1 → XP_063124698.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X4