Aggrecan cleaved by aggrecanases and matrix metalloproteinases (MMPs). Aggrecan core protein has three globular domains (G1, G2 and G3). The N-terminal G1 domain interacts with hyaluronan with the help of a link protein. G1-VDIPEN341 and G1-NITEGE373 are G1-bearing N-terminal products generated by MMPs and aggrecanases, respectively. Sites cleaved by aggrecanases are shown as (A)–(E), and sites cleaved by MMPs are shown as 1–6. The dotted arrows are sites predicted based on SDS-PAGE analysis of Little et al.  and of Sandy and Verscharen . KS, keratansulfate rich region; CS, chondroitinsulfate rich region. Residues and numbering in parentheses indicate bovine sequences.