ADAMTS4

ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), also known as aggrecanase1, is a member of the family of secreted zinc proteases with a multidomain structure. The protein precursors consist of a signal peptide and the following domains: pro, catalytic, disintegrin-like, TS type 1 motif, cysteine-rich, and spacer. It is the only ADAMTS identified that has one TS type I motif. It is an active protease effectively cleaving α2-macroglobulin and aggrecan at multiple sites, and is inhibited by TIMP3 with inhibition constants in subnanomolar range. It receives great attention due to the elevation in its mRNA level after treatment with Interleukin1. However, in a mouse model of osteoarthritis, ADAMTS4 knockout mice did not exhibit any significant protective effect. ADAMTS4 consists of a signal peptide (aa 1 to 51), a pro domain (aa 52 to 212) and a mature chain (aa 213 to 837) containing the following domains: catalytic (aa 218 to 425), disintegrin (aa 437 to 519), TSP type 1 (aa 520 to 575), Cysrich (aa 577 to 685) and spacer (aa 686 to 837) . The amino acid sequence of rhADAMTS4 is 100%, 97% and 94% identical to that of chimpanzee, dog, and mouse/rat/bovine.