Map3k1 mitogen-activated protein kinase kinase kinase 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Map3k1provided by RGD
Full Name: mitogen-activated protein kinase kinase kinase 1provided by RGD
Primary source: RGD:620966
See related: Ensembl:ENSRNOG00000013177 AllianceGenome:RGD:620966
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: Mekk1
Summary: Enables several functions, including JUN kinase kinase kinase activity; protein kinase binding activity; and ubiquitin-protein transferase activity. Involved in several processes, including cellular protein metabolic process; positive regulation of MAPK cascade; and positive regulation of viral transcription. Located in cytoplasm and membrane. Colocalizes with cytoskeleton. Human ortholog(s) of this gene implicated in 46,XY sex reversal 6 and breast cancer. Orthologous to human MAP3K1 (mitogen-activated protein kinase kinase kinase 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Spleen (RPKM 167.6), Kidney (RPKM 149.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 2q14

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	2	NC_086020.1 (45081889..45150555, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	2	NC_051337.1 (43348572..43414706, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	2	NC_005101.4 (43329516..43393203, complement)

Chromosome 2 - NC_086020.1 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: 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?

MEKK1 may play a role in promoting the brain damage following intracerebral hemorrhage
Title: MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage.
Zinc-deficient rats had significantly decreased protein expression of pMEK, pERK1/2, and pCREB in the hippocampus.
Title: Depressed hippocampal MEK/ERK phosphorylation correlates with impaired cognitive and synaptic function in zinc-deficient rats.
Signaling pathways that augment or diminish beta-cell MEKK-1 activity may aid in the generation of novel therapeutic strategies in the treatment of type 1 diabetes.
Title: The MAPK kinase kinase-1 is essential for stress-induced pancreatic islet cell death.
MEK is an effector of v-Src-induced cytoskeleton disruption, participating in v-Src-induced antagonism of the cellular function of Rho
Title: MEK mediates v-Src-induced disruption of the actin cytoskeleton via inactivation of the Rho-ROCK-LIM kinase pathway.
Ras, Mek, PKC iota, and Rac 1 are involved in PKCbetaII induction of cell invasiveness through a signal pathway
Title: Protein kinase C (PKC) betaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway.
ischemia/reperfusion induces caspase-3 mediated proteolytic cleavage of MEKK1 and promotes p53 transcriptional activity via JNK-independent mechanisms
Title: Caspase-3 mediated cleavage of MEKK1 promotes p53 transcriptional activity.
We identified the upstream kinase MEKK1 as an activator of both the ERK1/2 and JNK2 pathways, whereby the ERK1/2 kinase MEK1 and the JNK kinase MKK7 bind to MEKK1 in a competing fashion.
Title: MEKK1 controls neurite regrowth after experimental injury by balancing ERK1/2 and JNK2 signaling.
identification of MEKK1 as a further member of the growing family of ceramide-activated protein kinases
Title: Differential binding of ceramide to MEKK1 in glomerular endothelial and mesangial cells.
functions not only as an upstream activator of the ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD domain, providing a negative regulatory mechanism for decreasing ERK1/2 activity
Title: The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2.
MEKK1 probably activates a transcriptional partner of c-Jun whose activity is maintained or increased in the presence of the rat cholecystokinin 1 receptor but repressed in the presence of the mouse cholecystokinin 1 receptor.
Title: Cholecystokinin 1 receptor modulates the MEKK1-induced c-Jun trans-activation: structural requirements of the receptor.

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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

REN28005 (e-PCR)
- UniSTS:352805

ECD05748 (e-PCR)
- UniSTS:286810

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables JUN kinase kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables JUN kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cytoskeletal protein binding	ISO Inferred from Sequence Orthology more info
enables mitogen-activated protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables mitogen-activated protein kinase kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables sphingolipid binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-protein transferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within apoptotic mitochondrial changes	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within camera-type eye 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 mechanical stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within epithelial cell morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within eyelid development in camera-type eye	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within morphogenesis of an epithelial sheet	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of actin filament bundle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	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 MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of actin filament polymerization	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of viral transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in protein polyubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in ubiquitin-dependent protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within wound healing	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
part_of filamentous actin	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 1

Names: MAPK/ERK kinase kinase 1; MEK kinase 1; MEKK 1; mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase

NP_446339.2

EC 2.7.11.25

XP_038957510.1

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_053887.2 → NP_446339.2 mitogen-activated protein kinase kinase kinase 1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

F1M778, H9BFG7

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_086020.1 Reference GRCr8

Range

45081889..45150555 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039101582.2 → XP_038957510.1 mitogen-activated protein kinase kinase kinase 1 isoform X1

UniProtKB/TrEMBL

F1M778, H9BFG7

Related

ENSRNOP00000017968.3

Conserved Domains (2) summary

cd06630
Location:1223 → 1490

STKc_MEKK1; Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1

cd16494
Location:430 → 485

RING-CH-C4HC3_ZSWM2; RING-CH finger, H2 subclass (C4HC3-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins