A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is composed of 8 β-sheets, forming a beta-sandwich motif, and co-ordinates 2 or 3 calcium ions, which bind in an indentation formed by the first and final loops of the domain, on the membrane binding face.
C2 domains are frequently found coupled to enzymatic domains; for example, the C2 domain in PTEN, brings the phosphatase domain into contact with the membrane where it can dephosphorylate its substrate, 3,4,5 tetraphospho-inositol, without removing it from the membrane - which would be energetically very costly. In addition to this, phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring, also uses a C2 domain to bind to the membrane (e.g. 1e8w PDB entry).
C2 domains are also found in clostridial alpha toxins, where they are used to bring the catalytic phospholipase domain into contact with the plasma membrane, conferring the toxic activity on the protein. These are the only known examples of C2 domains in prokaryotes.
- C2 domain family in Pfam
- Phosphoinositide 3-kinase C2 family in Pfam
- UMich Orientation of Proteins in Membranes families/superfamily-47 - Orientations of C2 domains in membranes (OPM)