Gene: MAP3K4

Alternate names for this Gene: MAPKKK4|MEKK 4|MEKK4|MTK1|PRO0412

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. Several alternatively spliced transcripts encoding distinct isoforms have been described.

Gene is located in Chromosome: 6

Location in Chromosome : 6q26

Description of this Gene: mitogen-activated protein kinase kinase kinase 4

Type of Gene: protein-coding

rs9458121 in MAP3K4 gene and Alcoholic Intoxication, Chronic PMID 21956439 2012 Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q.

rs144240142 in MAP3K4 gene and Endometriosis PMID 28333195 2017 The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4.

rs12110787 in MAP3K4 gene and Rheumatoid Arthritis PMID 22491018 2013 Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.