A disintegrin and metalloproteinase (ADAM) is a family of gene products with sequence homology to snake venom metalloproteinases and disintegrins [1, 2]. Members of the family share several distinct protein modules, including a metalloprotease domain, a disintegrin domain, a cysteine-rich region and an EGF repeat [1, 2]. These proteins, however, perform essential functions in cell adhesion and fusion in diverse systems [3]. The heterodimeric sperm protein fertilin participates in sperm-egg fusion [4], while meltrin-K is involved in myoblast fusion [5]. The Drosophila Kuzbanian (KUZ) plays a role in axonal extension and neural cell fate in£ y neurogenesis [6, 7]. The protease activity of some members is apparently important in ectodomain shedding of molecules such as the tumor necrosis factor K and the Drosophila signalling molecule Notch [3]. The tumor necrosis factor (TNF)-K converting enzyme (TACE, ADAM17), for example, has a role in processing multiple cell surface proteins as revealed by analysis of knockout mice [8]. The ADAM family members are generally cell surface molecules with a transmembrane domain spanning the plasma membrane.

We report here a bunch of proteins with a metalloproteasedisintegrin domain and an additional distinct feature not present in other ADAM proteins, a thrombospondin type 1 (TSP1) motif. The TSP1 motifs are repeats conserved in TSP 1 and 2, which are multifunctional extracellular matrix (ECM) proteins implicated in cell adhesion, motility and growth. Thrombospondin is a major constituent of platelet K-granules. It is also secreted by a wide variety of epithelial and mesenchymal cells and the levels of thrombospondin are correlated with developmental changes in the embryo and the response to injury in the adult [9]. TSP1 motifs can also be found in several proteins in the complement cascade, properdin [10] and f-spondin, a protein involved in neural cell adhesion and neurite outgrowth [11].