PACE4A IS A UBIQUITOUS ENDOPROTEASE THAT HAS SIMILAR BUT NOT IDENTICAL SUBSTRATE-SPECIFICITY TO OTHER KEX2-LIKE PROCESSING ENDOPROTEASES

We describe here the isolation and characterization of a mouse cDNA for an isoform of PACE4 (PACE4A), which is a member of the Kex2 family of mammalian pro-protein processing endoproteases. Mouse PACE4A is deduced to be synthesized as a 946-amino acid precursor with a 141-amino acid prepropeptide. It is highly homologous to rat and human PACE4A in the primary sequence, especially within the subtilisin-like catalytic domain (>97% identity). The PACE4A mRNA was detected in all examined tissues and cell lines like furin and PC6A mRNAs. Coexpression experiments in COS-7 cells of PACE4A with provon Willebrand factor, complement pro-C3, or a prorenin mutant indicate that although PACE4A can cleave precursors at sites marked by the Arg-X-Lys/Arg-Arg consensus motif, its specificity is somewhat different from those of furin and PC6A.