CATHEPSIN-C FROM SCHISTOSOMA-JAPONICUM CDNA-ENCODING THE PREPROENZYMEAND ITS PHYLOGENETIC-RELATIONSHIPS

A cDNA encoding preprocathepsin C was isolated from adults of the asia n blood fluke Schistosoma japonicum. The deduced amino acid sequence o f S. japonicum cathepsin C comprised 458 amino acid residues; 22 NH2-t erminal residues corresponding to the signal peptide, 199 residues cor responding to the propeptide and 237 COOH-terminal residues correspond ing to the mature enzyme region. The amino acid sequence of this prepr ocathepsin showed 43% and 50% identity to that of human and rat, respe ctively. The preproenzyme shared only 59% identity with the sequence f or a cathepsin C reported from Schistosoma mansoni, differing from it in active-site residues and in its potential N-glycosylation sites. No rthern-blot analysis showed that S. japonicum cathepsin C was expresse d in greater quantities in female than in male parasites. Phylogenetic analysis utilizing the mature enzyme sequences of S. japonicum and ot her cathepsin Cs demonstrated that cathepsin Cs and cathepsin Bs share d a common ancestry. The unusually long prosegment observed in catheps in C from S. japonicum and from other species was compared to that of cathepsin Bs and cathepsin Ls. The extension contained two blocks of r esidues which were highly conserved among cathepsin Cs. The COOH termi nus of the prosegment exhibited a composite of features present in the prosegments of cathepsin Ls and cathepsin Bs. Most significantly, giv en the common ancestry of cathepsin Bs and cathepsin C, the prosegment of cathepsin C included ERFNIN-like motifs and other residues more ch aracteristic of non-cathepsin-B-like members of the papain superfamily such as cathepsin L.