Disintegrin and metalloproteinase with thrombospondin motifs 4 (for ADAMTS4) and Disintegrin and metalloproteinase with thrombospondin motifs 5 (for ADAMTS5) (ADAMTS4 and ADAMTS5)

ADAMTS4 and ADAMTS5 are secreted extracellular matrix metalloproteinases belonging to the ADAMTS family. Their primary function is to cleave large proteoglycans such as aggrecan, thereby driving cartilage matrix degradation, especially in osteoarthritis. Structurally, both proteins contain a signal peptide, pro-domain, catalytic metalloproteinase domain, disintegrin-like domain, and additional C-terminal ancillary domains including thrombospondin type 1 repeats, cysteine-rich domains, and spacer regions. They require activation via furin-mediated removal of the pro-domain and are strongly regulated by endogenous inhibitors, primarily TIMP-3. Their expression and activity are associated with cartilage erosion, cardiovascular disease, and other forms of tissue remodeling, making them critical therapeutic targets for musculoskeletal and cardiovascular disorders.

Other names

Aggrecanase-1Aggrecanase-2

Inhibition of catalytic metalloproteinase domain by specific inhibitors (e.g., batimastat, biphenyl compounds). Endogenous inhibition via TIMP-3 binding to the active site and ancillary domains.