Gene organization and alternative splicing of human prohormone convertase PC8

The mammalian Ca2+-dependent serine protease prohormone convertase PC8 is e xpressed ubiquitously, being transcribed as 3.5, 4.3 and 6.0 kb mRNA isofor ms in various tissues. To determine the origin of these various mRNA isofor ms we report the characterization of the human PC8 gene, which has been pre viously localized to chromosome 11q23-24. Consisting of 16 exons, the human PC8 gene spans approx. 27 kb. A comparison of the position of intron-exon junctions of the human PC8 gene with the gene structures of previously repo rted prohormone convertase genes demonstrated a divergence of the human PC8 from the highly conserved nature of the gene organization of this enzyme f amily. The nucleotide sequence of the 5'-flanking region of the human PC8 i s reported and possesses putative promoter elements characteristic of a CC- rich promoter. Further supporting the potential role of a GC-rich promoter element, multiple transcriptional initiation sites within a 200 bp region w ere demonstrated. We propose that the various mRNA isoforms of PC8 result f rom the inclusion of intronic sequences within transcripts.