InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Map3k4

Summary

InnateDB Gene

IDBG-136472.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Map3k4

Gene Name

mitogen-activated protein kinase kinase kinase 4

Synonyms

D17Rp17; D17Rp17e; MAPKKK4; Mek4b; MEKK 4; Mekk4; mKIAA0213; MTK1; RP17; Rp17a; Tas

Species

Mus musculus

Ensembl Gene

ENSMUSG00000014426

Encoded Proteins

IDBP-136474

mitogen-activated protein kinase kinase kinase 4

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation from Orthologs

Summary

PMID 17726008

[Homo sapiens] MAP3K4 (MEKK4) dimerization is regulated both positively and negatively by its interaction with specific proteins. GSK3B negatively regulates MAP3K4 stimulation of MAPK14 (P38) and MAPK8 (JNK) activity.

PMID 18775659

[Homo sapiens] MAP3K4 sequesters RIPK2 to inhibit the NOD2:RIPK2 complex from activating NF-kappaB signalling pathways.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000085511:
The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Two alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 17:12227621-12318660

Strand

Reverse strand

Band

Transcripts

ENSMUST00000089058

ENSMUSP00000086459

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	10 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0001890	placenta development
GO:0006468	protein phosphorylation
GO:0010225	response to UV-C
GO:0010468	regulation of gene expression
GO:0019100	male germ-line sex determination
GO:0035556	intracellular signal transduction
GO:0043507	positive regulation of JUN kinase activity
GO:0048263	determination of dorsal identity
GO:0060718	chorionic trophoblast cell differentiation
GO:1900745	positive regulation of p38MAPK cascade

Cellular Component

GO:0005737	cytoplasm
GO:0048471	perinuclear region of cytoplasm

Orthologs

Species

Homo sapiens

Bos taurus

Gene ID

Gene Order

ENSG00000085511

View Gene Order

ENSBTAG00000020079

Not yet available

Pathways

NETPATH

REACTOME

KEGG

mmu04912

GnRH signaling pathway pathway

mmu04010

MAPK signaling pathway pathway

INOH

PID NCI

Pathway Predictions based on Human Orthology Data

NETPATH

NetPath_4

EGFR1 pathway

NetPath_8

Wnt pathway

NetPath_18

IL6 pathway

REACTOME

KEGG

hsa04912

GnRH signaling pathway pathway

hsa04010

MAPK signaling pathway pathway

INOH

PID NCI

p38_mkk3_6pathway

p38 MAPK signaling pathway

Cross-References

SwissProt

O08648

TrEMBL

Q80U64 Q9CRU1

UniProt Splice Variant

Entrez Gene

26407

UniGene

Mm.28587 Mm.413344

RefSeq

NM_011948 XM_006523330 XM_006523331

OMIM

CCDS

CCDS37435

HPRD

IMGT

MGI ID

MGI:1346875

MGI Symbol

Map3k4

EMBL

AK014185 AK122219 BC058719 U66240 U85607 U85608

GenPept

AAC08286 AAC53126 AAC53127 AAH58719 BAB29197 BAC65501

RNA Seq Atlas

26407