The proteolysis of calmodulin by fungal protease (type XIX) was greatly enhanced in the presence of dGTP and MS2 RNA. Whereas, only moderate proteolytic activation on bacterial proteases (type XXVI) was observed in the presence of MS2 RNA. No appreciable proteolysis of calmodulin by bacterial protease (type IX) was observed. Proteolytic fragments of calmodulin cleaved by fungal protease exhibited unusual low mobility during SDS-polyacrylamide gel electrophoresis. Similar decreased electrophoretic mobility was also noted in the proteolytic fragments of other Ca2(+)-binding proteins including S-100A protein and parvalbumin.