|Institutional Source||Beutler Lab|
|Gene Name||mitogen-activated protein kinase kinase kinase 4|
|Synonyms||D17Rp17, D17Rp17e, RP17, MAPKKK4, Mekk4, MTK1, Tas|
|Essential gene?||Probably essential (E-score: 0.947)|
|Stock #||R1997 (G1)|
|Chromosomal Location||12227621-12318660 bp(-) (GRCm38)|
|Type of Mutation||critical splice donor site (2 bp from exon)|
|DNA Base Change (assembly)||A to T at 12254995 bp (GRCm38)|
|Amino Acid Change|
|Ref Sequence||ENSEMBL: ENSMUSP00000086459 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000089058]|
|Coding Region Coverage||
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Homozygous null mice exhibit some perinatal lethality and survivors appear smaller. On certain genetic backgrounds, heterozygous X/Y mice may develop as phenotypic females or hermaphrodites. The sex-reversal phenotype is dependent on a combination of strain-specific autosomal and Y-linked alleles. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Map3k4||
(F):5'- TCTGACTGTGAGCGCAAGAG -3'
(R):5'- CAATGCTGCCACAGGAAAG -3'
(F):5'- CTGTGAGCGCAAGAGAAAGAAC -3'
(R):5'- TGCCACAGGAAAGGACTGCTC -3'