Fig. 3

Amino acid alignment of human TRPM3 isoform-k (hK) and mouse TRPM3 isoform-w (mW). Partial amino acid alignments of mouse TRPM3 isoform-d (mD, alias mα2) and isoform-a (mA, alias mα1) are included. Bars denote identical amino acids. Colons denote similar amino acid changes. Single dots denote dissimilar amino acid changes. Dashes denote gaps. CaM1, first calmodulin binding-site in mD/mα2 (K41-P61, shaded gray). Gray-shaded bars denote protein domains as follows. TRPM-start, consensus start-motif of the ~ 700 amino acid TRPM domain. CaM2–5, calmodulin binding-sites 2–5 in hK, mW, and mD/mα2. An in silico CaM6 binding-site (P966-L987) overlapping S4 in mW is underlined. CaM/S100A1 and PI(4,5)P2 binding-sites in hK (A35-K124, H291-G382) are also underlined. Putative PH-like domains and PI(4,5)P2 binding-sites (K302-R311, K596-K611) in hK are shown in italics. ICF, indispensable for channel function domain (mD/α2), S1-S6, transmembrane α-helical segments, P-loop, canonical pore-forming loop, TRP1–2, TRP-domain containing TRP-box 1 (1127-WKFQR-1132) and TRP-box 2 (1144-LPPPL-1148), and C-C, coiled-coil domain (R1219-T1271). /\ indicates location of ‘long-pore’ region of mA/α1 that is absent in hK, mW, and mD/mα2. Alternative methionine translation start-sites (M1, M65, M154), cataract-associated mutations (p.I65M, p.R1470T), and functionally important amino-acids in the CaM/S100A1 binding-site (K45, R67, K71, R72), CaM2 binding-site (K198, K200, K205, K209), ICF domain (L516-Y525), S1 helix (Y976, Y780, Y783), S3 helix (E939), S4 helix (W980, R983, D986, G989), and P-loop region (E1055) are shown in red font. A synthetic-peptide (L1030-N1043) located in the third extracellular loop (P-loop) of hK used to raise a polyclonal antibody (TM3E3) is shaded gray. The C-terminal sequence of the truncated hTRPM3–1325 isoform (hS) is indicated. Asterisks denote translation stop-sites