Evolutionary divergence and functions of the ADAM and ADAMTS gene families.
The 'A-disintegrin and metalloproteinase' ( ADAM ) and 'A-disintegrin and metalloproteinase with thrombospondin motifs' ( ADAMTS ) genes make up two similar, yet distinct, gene families. The human and mouse genomes contain 21 and 24 putatively functional protein-coding ADAM genes, respectively, and 24 versus 32 putatively functional protein-coding ADAMTS genes, respectively. Analysis of evolutionary divergence shows that both families are unique. Each of the two families can be separated, if need be, into groups of more closely related members: six subfamilies for ADAM , four subfamilies for ADAMTS. The presence of both disintegrin and peptidase domains within the ADAM and ADAMTS proteins implies multiple biological roles within the cell. Membrane-anchored ADAM proteins are best known for their role in activating zymogens--including tumour necrosis factor-alpha, epidermal growth factor (EGF) and amyloid precursor protein (APP). ADAM proteins can also participate in cell adhesion via their interaction with integrins in neighbouring cells. ADAMTS are secreted proteins that participate in extracellular matrix maintenance by way of their cleavage of procollagen and proteoglycans. ADAMTS proteins also are involved in coagulation by cleaving von Willibrand factor precursor protein. ADAM and ADAMTS proteins participate in a wide range of cellular processes, including cell adhesion and migration, ectodomain shedding, proteolysis, development, ovulation and angiogenesis. Because these enzymes are believed to play an important role in a number of pathologies, including Alzheimer's disease, rheumatoid arthritis, atherosclerosis, asthma and cancer progression, the products of the ADAM and ADAMTS genes represent promising drug targets for the prevention and management of a number of human diseases.
Brocker
Chad N
CN
Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
Vasiliou
Vasilis
V
Nebert
Daniel W
DW
D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D006801:Humans; D005810:Multigene Family
D051722:ADAM Proteins