Domain structure of proteases that participate in aggrecan core protein degradation. The mature (active) forms of the enzymes are illustrated. The catalytic units are shown in magenta, with the catalytic amino acid residues (C, H, N, D,S) or co-factor (Zn2+) indicated. Ancillary domains, some of which are involved in substrate recognition, are also depicted. TS, thrombospondin-like; PEF, penta EF-hand (calcium binding domain); IGFBP, insulin-like growth factor binding protein-like; PDZ, protein/protein interaction domain. The functional form of calpain is a heterodimer of the large and small subunit shown, and that of HtrA1 is a homotrimer.