FIGURE 8.
Aligned amino acid sequences of exon 12A in metazoan Cav3 channel homologs. Exon 12a codes for novel extracellular turret residues from the middle of domain II, segment five through the descending pore helix to five amino acids upstream of selectivity filter glutamate (purple) residue, and invariant aspartate residue after it, conserved in all calcium channels (orange residue). Exon 12a is flanked by conserved charged residues (red), surrounding a set of variable amino acids, outside of very conserved cysteine (yellow) residues. Exon 12a is ∼40 aa with a tri-cysteine motif (CXXC … C). Vertebrate T-type channels resemble the size of exon 12A in length (∼39 aa) but are missing the most downstream two cysteines of invertebrate exon 12a. Animals bearing T-type channels below the protostome invertebrates (placozoan and cnidarians) have zero or two cysteines in exon 12a and lack an exon 12b. Most protostome invertebrates possess an alternative exon 12b (see Fig. 9) turret in addition to exon 12a, and these are highlighted and outlined.