The second EGF-like domain of MFG-E8 contains an integrin-binding motif, namely Arg-Gly-ASP (RGD) sequence. The RGD motif is conserved in all known MFG-E8 sequence in different species. It can bind to αvβ3 and αvβ5 integrins. MFG-E8 was characterized as a peripheral membrane protein, although there was no apparent hydrophobic transmembrane domain, and bind directly to MFGM or cell membrane. The MFG-E8 binds to anionic phospholipids, especially phosphatidylserine, on the second C (C2) domain independent of Calcium ions.