Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking

ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca(2+)-binding protein and interacts with a variety of proteins in a Ca(2+)-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca(2+)-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.