General structural features of the TRPM2 channel. The cartoon depicts a single putative subunit of the TRPM2 channel. The N terminus contains four homologous regions (MHR, blue) as well as a CaM-binding IQ-like motif. Six transmembrane segments (S1–S6) are shown as cylinders, and there is a pore loop domain between S5 and S6. The C terminus encompasses a coiled-coil domain (CC, yellow) and a Nudix-like domain, or NUDT9 homology domain (NUDT9-H, green). ADPR is hydrolyzed to ribose-5-phosphate and AMP by the NUDT9-H.