Version 5.4
Homo sapiens Gene: MAP3K4
Summary
InnateDB Gene IDBG-98770.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol MAP3K4
Gene Name mitogen-activated protein kinase kinase kinase 4
Synonyms MAPKKK4; MEKK 4; MEKK4; MTK1; PRO0412
Species Homo sapiens
Ensembl Gene ENSG00000085511
Encoded Proteins
IDBP-98772
mitogen-activated protein kinase kinase kinase 4
IDBP-98776
mitogen-activated protein kinase kinase kinase 4
IDBP-98780
mitogen-activated protein kinase kinase kinase 4
IDBP-246259
mitogen-activated protein kinase kinase kinase 4
IDBP-388196
mitogen-activated protein kinase kinase kinase 4
IDBP-593537
mitogen-activated protein kinase kinase kinase 4
IDBP-601624
mitogen-activated protein kinase kinase kinase 4
IDBP-593243
mitogen-activated protein kinase kinase kinase 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 17726008
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
MAP3K4 sequesters RIPK2 to inhibit the NOD2:RIPK2 complex from activating NF-kappaB signalling pathways.
Entrez Gene
Summary 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 6:160991727-161117385
Strand Forward strand
Band q26
Transcripts
ENST00000348824 ENSP00000297332
ENST00000366920 ENSP00000355887
ENST00000366919 ENSP00000355886
ENST00000392142 ENSP00000375986
ENST00000446500
ENST00000448119 ENSP00000390508
ENST00000490904 ENSP00000446303
ENST00000542952 ENSP00000439377
ENST00000544041 ENSP00000445018
ENST00000542851
ENST00000540205
ENST00000543421
ENST00000541901
ENST00000544733
ENST00000536852
ENST00000539610
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 43 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.
Experimentally validated
Total 43 [view]
Protein-Protein 41 [view]
Protein-DNA 2 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 8 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine 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:0045087 innate immune response (InnateDB)
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
Mus musculus
Bos taurus
Gene ID
Gene Order
ENSMUSG00000014426
View Gene Order
ENSBTAG00000020079
Not yet available
Pathways
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
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.390428
RefSeq NM_001291958 NM_001301072 NM_005922 NM_006724 XM_005266988 XM_005266989
HUGO
OMIM
CCDS CCDS34565 CCDS34566 CCDS75544
HPRD 03886
IMGT
EMBL
GenPept
RNA Seq Atlas

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca