mitogen-activated protein kinase kinase kinase 4 (MAPK/ERK kinase kinase 4, MEK kinase 4, MAP three kinase 1, MAP3K4, KIAA0213, MAPKKK4, MEKK4, MTK1)

Function

• component of a protein kinase signal transduction cascade
• activates the CSBP2, P38 & JNK MAPK pathways, but not the ERK pathway
• specifically phosphorylates & activates MAP2K4 & MAP2K6
• binds both upstream activators & downstream substrates in multimolecular complexes
• interacts with AXIN1 & DIXDC1
• interaction with DIXDC1 prevents interaction with AXIN1
• N-terminal autoinhibitory domain interacts with C-terminal kinase domain, inhibiting kinase activity, & preventing interaction with its substrate, MAP2K6
• GADD45 proteins activate the kinase by binding to the N-terminal domain
• activated by phosphorylation on Thr-1504

ATP + a protein <--> ADP + a phosphoprotein

Cofactor: Mg+2

Structure

• belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
• contains 1 protein kinase domain

Alternative splicing

named isoforms=2

Expression

• expressed in heart, placenta, skeletal muscle & pancreas > other tissues

More general terms

• MAP3K/MEKK

Database

• UniProt: http://www.uniprot.org/uniprot/Q9Y6R4.html
• OMIM: https://mirror.omim.org/entry/602425
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4216