The peptidase C80 family includes self-cleaving proteins that are precursors of bacterial toxins such as the Vibrio cholerae RTX self-cleaving toxin, as well as the major virulence factors of Clostridium difficile multidomain toxins, TcdA and TcdB. These toxins contain a cysteine protease domain (CPD) that autoproteolytically releases a cytotoxic effector domain upon binding intracellular inositol hexakisphosphate. This family also contains filamentous hemagglutinin family cysteine protease C80 domains, that are located at the C-terminus. All domains in this family contain the characteristic Cys/His residues in the active site. Site-directed mutagenesis has identified functional residues Asp/His/Cys in Clostridium toxin B and His/Cys in cholera RTX toxin.