CDNA STRUCTURE, TISSUE DISTRIBUTION, AND CHROMOSOMAL LOCALIZATION OF RAT PC7, A NOVEL MAMMALIAN PROPROTEIN CONVERTASE CLOSEST TO YEAST KEXIN-LIKE PROTEINASES

By using reverse transcription coupled PCR on rat anterior pituitary R NA, we isolated a 285-bp cDNA coding for a novel subtilisin/kexin-like protein convertase (PC), called rat (r) PC7, By screening rat spleen and PC12 cell lambda gt11 cDNA libraries, we obtained a composite 3,5- kb full-length cDNA sequence of rPC7, The open reading frame codes for a prepro-PC with a 36-amino acid signal peptide, a 104-amino acid pro segment ending with a cleavable RAKR sequence, and a 747-amino acid ty pe I membrane-bound glycoprotein, representing the mature form of this serine proteinase. Phylogenetic analysis suggests that PC7 represents the most divergent enzyme of the mammalian convertase family and that it is the closest member to the yeast convertases krp and kexin. Nort hern blot analyses demonstrated a widespread expression with the riche st source of rPC7 mRNA being the colon and lymphoid-associated tissues , In situ hybridization revealed a distinctive tissue distribution tha t sometimes overlaps with that of furin, suggesting that PC7 has wides pread proteolytic functions, The gene for PC7 (Pcsk7) was mapped to mo use chromosome 9 by linkage analysis of an interspecific backcross DNA panel.