The transient receptor potential melastatin (TRPM) subfamily of cation-permeable TRP channels is ubiquitously expressed in mammalian tissues. This family includes TRPM1-8. In addition to acting as a calcium-permeant channel, TRPM6 and TRPM7 possess an inherent serine/threonine kinase activity. TRPM7 specifically is involved with cellular magnesium homeostasis and neurotransmitter release. Due to the magnesium inhibition, TRPM7s ion channel activity is very low. TRPM7 has been implicated in cell proliferation and migration during cancer progression, and its expression levels correlate with prognosis in breast cancer. TRPM7 kinase activation leads to massive autophosphorylation of the C-terminal region, including phosphorylation of Ser-1493, Ser-1513, and Ser-1569. Both Ser-1513 and Ser-1569 phosphorylation is required for kinase activity, and phosphorylation of Ser-1513 may inhibit Caspase-mediated cleavage of the C-terminal tail. Thus, TRPM7 is a multifunctional transmembrane protein with roles in cell signaling, proliferation, migration, and death.
