TRPM6 belongs to the TRPM subfamily of cation channels, the members of which exhibit marked diversity in activation mechanisms and ion selectivity [39]. TRPM channels differ from other TRP subfamilies by virtue of a long, conserved N-terminus of unknown function and an extended C-terminus. Three of the TRPM cation channels are characterized by a C-terminal enzyme domain, which has led to these proteins being termed ‘‘chanzymes’’ [23].
Phylogenetic analysis of the TRPM subfamily based on amino acid sequence similarities has indicated four distinct groups amongst the eight family members.
One of these subgroups consists of TRPM6 and its closest homologue TRPM7. Both proteins share the unique feature of a C-terminal serine/threonine protein kinase domain resembling those of the eukaryotic elongation factor 2 (eEF-2) kinase and other akinases.