Identification of a Second Human Subtilisin-Like Protease Gene in the fes/fps Region of Chromosome 15

A cDNA encoding a novel human subtilisin-like protease was identified by a polymerase chain reaction (PCR) methodology. PCR primers were designed to be specific for the subfamily of eukaryotic subtilisin-like proteases with specificity for paried basic amino acid residue processing motifs. The gene encoding this protease, designated PACE4, also encoded a smaller subtilisin-related polypeptide derived by alternate mRNA splicing. The deduced PACE4 protein sequence contained a number of interesting features not present in other family members, including an extended signal peptide region, and a relatively large carboxyl-terminal cysteine-rich region with no obvious membrane anchor sequence. As with the fur gene product, the tissue distribution of PACE4 was widespread, with comparatively higher levels in the liver. An additional relationship to the fur gene product was shown by chromosomal localization studies. The close proximity of the fur and PACE4 genes on chromosome 15 suggests that these genes probably evolved from a common ancestor by gene duplication.