Multiple sequence alignment of TRPM proteins. Sequence alignment of TRPM2, TRPM4, TRPM5 and TRPM8 channel orthologues (hs: Homo sapiens, dr: Danio rerio, nv: Nematostella vectensis) calculated using Clustal Omega [54], with some manual adjustments. Conserved residues are highlighted according to percent of identity in Jalview [55]. Secondary structure elements (based on 6pus) are shown for hsTRPM2 above the sequences. Color coding follows that used in Figure 3B. Canonical Arg residues in the S4 segment (magenta) and residues of the selectivity filter (blue), the post-filter helix (green), and of the ADPR1 (orange) and Ca2+ binding sites (red) are highlighted in boxes. P-loop segment of the NUDT9-H domain is identified by gray bar.