Human cathepsins F and W: A new subgroup of cathepsins

Human cathepsin F is a recently described papain-like cysteine protease of unknown function. To investigate the evolutionary relatedness to other huma n cathepsins, we determined the genomic organization and the chromosomal lo calization of cathepsin F and isolated its putative promoter region. The ge ne of human cathepsin F (CTSF) is composed of twelve exons and eleven intro ns and was found to be similar to that of cathepsin W but different from th e cathepsins K, S, L, O, B, and C, The splice sites of nine out of the elev en introns were identical to those determined in the cathepsin W gene (CTSW ), whereas introns one and ten were unique for CTSF. The 4.7 kb gene was ma pped to the long arm of chromosome 11 at position q13.1-3, a locus shared w ith CTSW, Phylogenetic analysis of human cathepsin protein sequences demons trated that (i) cathepsins F and W are evolutionarily separated from other human cathepsins, and (ii) cysteine proteases closely related to human cath epsin W sind F are also expressed in parasites and mammals. Based on these phylogenetic findings, on the presence of a particular protein motif ("ERFN AQ") in the propeptides of cathepsins F and W as well as the genomic: organ ization and chromosomal localization of their genes, we concluded that F an d W form a novel subgroup of cathepsin proteases, We suggest the naming "ca thepsin F-like" proteases distinct from the previously described cathepsins "L- and B-like" subgroups, (C) 1999 Academic Press.