ADAM-2, also known as PH-30?and Fertilin-? was first described as a sperm-egg fusion protein from guinea pig. A member of the metalloproteinase family containing disintigrin-like domains (ADAMs), the function of ADAM-2 is still poorly understood. Unlike ADAM-1, ADAM-2 does not contain the canonical HExxHxxxxxH zinc metalloproteinase motif, and is not thought to be proteolytically active. Like the other ADAMs, ADAM-2 domain structure consists of a signal sequence followed by a propeptide domain, a metalloproteinase domain, a disintegrin domain cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic domain. Three isoforms of ADAM-2 are reported to date, which differ in the beginning of the metalloproteinase domain and cysteine-rich domain. The sequences are coded from intronless genes. The longest ADAM-2 message encodes a protein of 735 amino acids, with a predicted mass of 82.5 kDa and a pI of 5.73. The 716 amino acid form of ADAM-2 has a deletion in the start of the metalloproteinase domain, relative to the longer form, and has a predicted mass of 80.2 kDa and pI of 5.75. The shorter form of 579 amino acids shared the deletion in the MP domain, and also has a deletion in the cystein-rich domain. Localized on the surface of sperm, the ADAM-2 isoforms are thought to form a heterodimer with ADAM-1 (fertilin-a), and facilitate sperm-egg fusion, although there is some controversy about the precise actions the proteins play. Integrin a6? on the egg surface is thought to dock with a QDECD motif in the disintegrin domain of ADAM-2, and there is some speculation that ADAM-1/ADAM-2 heterodimewr initiated ADAM-3 production on the cell surface.