C2 calcium-dependent membrane targeting The C2 domain is a Ca2+-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies ofthe C1 domain in Protein Kinase C (that bind phorbol esters and diacylglycerol) (see <db_xref db="PROSITEDOC" dbkey="PDOC00379"/>)and the protein kinase catalytic domain (see <db_xref db="PROSITEDOC" dbkey="PDOC00100"/>). Regions withsignificant homology [<cite idref="PUB00002925"/>] to the C2-domain have been found in many proteins.The C2 domain is thought to be involved in calcium-dependent phospholipidbinding [<cite idref="PUB00002815"/>] and in membrane targetting processes such as subcellular localisation. <p>The 3D structure of theC2 domain of synaptotagmin has been reported[<cite idref="PUB00000918"/>], the domain forms an eight-stranded beta sandwich constructed around a conserved 4-stranded motif, designated a C2 key [<cite idref="PUB00000918"/>]. Calcium binds ina cup-shaped depression formed by the N- and C-terminal loops of theC2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca²⁺-binding loops are located at the end of an 8 stranded antiparallel beta sandwich. </p>