InterPro domain: IPR019448

The C2 domain is one of the most prevalent eukaryotic lipid-binding domainsdeployed in diverse functional contexts. Many C2 domainsbind directly to membrane lipids and display a wide range of lipidselectivity, with preference for anionic phosphatidylserine (PS) andphosphatidylinositol-phosphates (PIPs).

Despite their limited sequence similarity, all C2 domains contain at theircore a compact beta-sandwich composed of two four-stranded beta sheets withhighly variable inter-strand regions that might contain one or more alpha-helices.

The NT-type C2 domain shows a diverse range of domain architectures but it isnearly always found at the N-termini of proteins that contain it. Hence, ithas been named the N-terminal C2 (NT-C2) family. It is typically coupled witha coiled-coil domain, that could mediate di/oligo-merization and the DIL(Dilute) domain. It is also coupled with the Calponinhomology (CH) domain in EHBP1 proteins, Filamin/ABP280repeats and Mg2+ transporter MgtE N-terminal domain inproteins from chlorophyte algae such as Micromonas and Ostreococcus tauri.Thus, a common theme across the NT-type C2 domain proteins is the combinationto several different domains with microfilament-binding or actin-related roles(i.e. such as CH, DIL, and Filamin). Other conserved groups of the NT-type C2proteins prototyped by EEIG1, PMI1, and SYNC1 have their own distinct C-terminal conserved extensions that are restricted to these groups and mightmediate specific interactions. The primary function of the NT-type C2 domainappears to be the linking of actin/microfilament-binding adaptors to themembrane and to act as a link that tethers endosomal vesicles to thecytoskeleton in course of their intracellular trafficking [ 1 , 2 ].

1. Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes. Gene 469, 18-30
2. RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes. PLoS Genet. 12, e1006093