ADAM, A WIDELY DISTRIBUTED AND DEVELOPMENTALLY-REGULATED GENE FAMILY ENCODING MEMBRANE-PROTEINS WITH A DISINTEGRIN AND METALLOPROTEASE DOMAIN

Fertilin alpha and beta, previously known as PH-30 alpha and beta, are two subunits of a guinea pig sperm integral membrane protein implicat ed in sperm-egg binding and fusion. They are derived from sequence-sim ilar precursors which contain a metalloprotease-like and a disintegrin -like domain and which are related to a family of metalloprotease and disintegrin domain-containing snake venom proteins. We report here the cloning, sequencing, and characterization of mouse fertilin alpha and beta as well as five additional sequence-similar cDNAs from guinea pi g and mouse testis. We name this gene family ADAM, for proteins contai ning A Disintegrin And Metalloprotease domain, and in honor of its dua l origins in the fields of snakes and fertility. In situ hybridization demonstrated that, in testis, RNA encoding these ADAMs is expressed o nly in spermatogenic cells and that this expression is developmentally regulated. PCR analysis of mouse tissue cDNA showed that these ADAMs display different patterns of tissue distribution. Some ADAMs (e.g., f ertilin alpha) have the consensus active-site sequence for a zinc-depe ndent metalloprotease in their metalloprotease-like domain. All have a disintegrin-like domain, which could bind integrins or other receptor s. Some have sequences which may be active in membrane fusion. All enc ode potential membrane-spanning domains. Searches of sequence database s revealed that additional mammalian members of the ADAM gene family h ave been cloned from a variety of tissues. Thus, the ADAMs are a large , widely expressed, and developmentally regulated family of proteins w ith multiple potential functions in cell-cell and cell-matrix interact ions. (C) 1995 Academic Press, Inc.