Putative anionic clusters surround the activation regions of prethrombin-2 and protein C (PC). The acidic residues D14l, E14e, and E18 are positioned around the proteolytically sensitive R15 of prethrombin-2 (PDB: 3SQE). PC has comparable residues at E160, D167, and D172 that may also function as an anionic cluster around the reactive R169. For these proteins, cleavage at the ¹⁵R-I¹⁶ (prethrombin-2) or the ¹⁶⁹R-L¹⁷⁰ (PC) peptide bond is an important part of the activation process.