The carboxy-terminal of rabphilin-3A consists of two C2 domains, A and B, and the amino-terminal (residues 45-170) contains a cysteine-rich rich region with two zinc finger motifs. Rabphilin-3A belongs to a family of other carboxy-terminal type (C-type) tandem C2 proteins, which includes synaptotagmins and Doc2. Rabphilin is expressed in neuroendocrine cells and co-localizes with Rab3A on synaptic vesicles and chromaffin granules. Rabphilin-3A binds Rab3a/GTP/Mg+ within amino-terminal residues 45 and 170. Rabphilin-3A binds calcium ions and phosphatidylinositol 4,5-bisphophate containing lipid vesicles within its C2 domains. Rabphilin-3A is a positive regulator of calcium dependent exocytosis, while Rab3a is a negative regulator of exocytosis. Although rabphilin-3A associates with Rab3a, they seem to influence exocytosis independently of each other. Rabphilin-3A effects are likely mediated through interactions with an unknown factor that recognizes the Rab3 binding domain.
