ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain

Abstract

Fertilin alpha and beta, previously known as PH-30 alpha and beta, are two subunits of a guinea pig sperm integral membrane protein implicated in sperm-egg binding and fusion. They are derived from sequence-similar 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 pig and mouse testis. We name this gene family ADAM, for proteins containing A Disintegrin And Metalloprotease domain, and in honor of its dual origins in the fields of snakes and fertility. In situ hybridization demonstrated that, in testis, RNA encoding these ADAMs is expressed only 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., fertilin alpha) have the consensus active-site sequence for a zinc-dependent metalloprotease in their metalloprotease-like domain. All have a disintegrin-like domain, which could bind integrins or other receptors. Some have sequences which may be active in membrane fusion. All encode potential membrane-spanning domains. Searches of sequence databases revealed that additional mammalian members of the ADAM gene family have been cloned from a variety of tissues. Thus, the ADAMs are a large, widely expressed, and developmentally regulated family of proteins with multiple potential functions in cell-cell and cell-matrix interactions.