Both the C2A and C2B domains of synaptotagmin I have a conserved basic residue at the tip of the Ca2+-binding pocket. A, Alignment of synaptotagmin I from human, rat, mouse, and Drosophila. Bars indicate β-sheets, ⊕ indicates the conserved basic residues, dots indicate Ca2+-binding residues, and open boxes indicate conserved hydrophobic residues. Within the alignment, conserved residues are shown in gray, and identical residues are boxed. B, Schematic representation of loops 1 and 3, which form the Ca2+-binding pockets of both C2 domains [adapted with permission from Fernandez et al. (2001), their Fig. 6, using the Drosophila sequence to show the conserved basic residues (⊕) examined in this study].