A disintegrin-like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS4 or aggrecanase 1) is a member of the ADAMTS family of multidomain proteins that has demonstrated metalloproteinase functions. The ADAMTS4 protein contains a prohormone convertase cleavage site, thrombospondin-1 like domain, cysteine-rich domain, and a propeptide domain. ADAMTS4 activity had been shown to be blocked by TIMP-1, 2, 3, and 4.
ADAMTS4 plays an important role in the cleavage of aggrecan, versican and brevican. Studies have determined that aggrecan is cleaved within the interglobular domain of aggrecan at sites Glu(373)-Ala(374) and Phe(342)-Glu(373). Aggrecan degradation has been linked to the development of rheumatoid arthritis, osteoarthritis, retinal diseases, Alzheimer's and other neurodegenerative diseases.