ADAMTS

ADAMTS, or A Disintegrin And Metalloproteinase with Thrombospondin motifs, refers to a family of secreted zinc-dependent metalloproteases that remodel the extracellular matrix. Members are soluble enzymes that function in the extracellular space and be involved in development, tissue remodeling, and disease. Each enzyme is produced as an inactive precursor with a signal peptide and propeptide that are cleaved to generate an active catalytic domain. The catalytic region contains the characteristic zinc-binding motif HEXGHXXGXXHD, and is followed by a disintegrin-like domain and one or more thrombospondin type 1 repeats, along with additional non-catalytic domains in some members.

The ADAMTS family includes numerous proteases (commonly designated ADAMTS1 through ADAMTS20 in humans). They target various extracellular substrates, notably proteoglycans such as aggrecan, versican, and brevican, contributing to cartilage biology and tissue integrity. Other members participate in procollagen processing (for example ADAMTS2, ADAMTS3, and ADAMTS14 act as procollagen N- or C-propeptidases), angiogenesis (ADAMTS1), and hemostasis (ADAMTS13 cleaves ultra-large von Willebrand factor multimers).

Genetic and clinical aspects emphasize the importance of the family. Mutations in ADAMTS2 cause dermatosparaxis-type Ehlers-Danlos syndrome; ADAMTS13 deficiency leads to inherited thrombotic thrombocytopenic purpura. Due to their roles in ECM remodeling and proteoglycan processing, ADAMTS enzymes are studied as potential targets in osteoarthritis and fibrotic diseases, with inhibitors and modulators explored in research settings.