Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review)

The ADAMs belong to a disintegrin-like and metalloproteinase-containing pro tein family that are zinc-dependent metalloproteinases. These proteins shar e all or some of the following domain structure: a signal peptide, a propep tide, a metalloproteinase, a disintegrin, a cysteine-rich, and an epidermal growth factor (EGF)-like domains, a transmembrane region, and a cytoplasmi c tail. ADAMs are widely distributed in many organs, tissues, and cells, su ch as brain, testis, epididymis, ovary, breast, placenta, liver, heart, lun g, bone, and muscle. These proteins are capable of four potential functions : proteolysis, adhesion, fusion, and intracellular signaling. Because the n umber of ADAM genes has grown rapidly and the biological functions of most members are unclear, this review analyzes the protein structures and functi ons, their activation and processing, their known and potential activities, and their evolutionary relationships. A sequence alignment of human ADAMs is compiled and their homology and physical data are calculated. The concei vable functions of ADAMs in reproduction, development, and diseases are als o discussed.