Active Metalloproteases of the A Disintegrin And Metalloprotease (ADAM) Family: Biological Function and Structure

The "a disintegrin and metalloproteases" (ADAMs) are membrane-anchored metzincins of the adamalysin subfamily. This review gives an overview over the biological function and structure of ADAMs focusing on members of the family that display proteolytic activity. ADAMs are involved in a range of human diseases such as cancer metastasis, inflammatory disorders, neurological disease or asthma. It is, however, often difficult to assign a definitive role to a specific member of the ADAM family in a given disease mechanism due to overlapping activities and redundancy in function, as shown in various knock-out studies. The review discusses the structural domains that are not directly linked to protease activity followed by a more detailed overview over the role of the metalloprotease domain. Different family members are critically reviewed with respect to their role in biological processes with particular emphasis on disease-relevant functions.