MAP3K6 is a member of the serine/threonine protein kinase family. The encoded kinase was identified by its interaction with MAP3K5/ASK, a protein kinase and an activator of c-Jun kinase (MAPK7/JNK) and MAPK14/p38 kinase. This kinase was found to weakly activate MAPK7, but not MAPK1/ERK or MAPK14. An alternatively spliced transcript variant has been found for this gene, but its biological validity has not been determined.
MAP3K6 and MAP3K5 share 45% amino acid sequence identity; their catalytic domains share 82% identity. The authors confirmed the interaction of MAP3K6 with MAP3K5 in vivo using coimmunoprecipitation. Recombinant MAP3K6 weakly activated the JNK but not the ERK or p38 kinase pathways.