The cDNA sequence of the human pro-hormone and pro-protein convertase PC1.
Using a probe consisting of the full-length cDNA sequence of the mouse pro-hormone convertase PC1 (mPC1), we isolated from a lambda gt10 human pituitary cDNA library a number of contiguous clones, of which composite sequence of 3.3-kb defined the complete coding sequence of human PC1 (hPC1). The cDNA sequence of hPC1 encodes a protein containing 753 amino acids and potentially two N-glycosylation sites, one carboxy-terminal amidation site, a cAMP-dependent protein kinase Ser phosphorylation site, a tyrosine kinase phosphorylation site, and an ArgGlyAsp (RGD) sequence. Like mPC1, the carboxy-terminal sequence of hPC1 exhibits an amphipathic domain potentially involved in membrane association. The coding region of hPC1 exhibits an overall 92.6% protein sequence identity to the mouse mPC1 sequence, with the highest homology (98%) found in the catalytic segment of the molecule (residues 84-399). Whereas Northern blot analysis of tissues obtained from mouse, rat and porcine demonstrated the presence of two mRNAs of 3 kb and 5 kb, Northern blots of human tissues and cells demonstrated the presence of a dominant transcript of 6.2 kb and the presence of smaller transcripts in some tissues. The major site of production of hPC1 seems to be the pituitary and brain, although detection was also possible in pancreas and heart.
Seidah
N G
NG
J.A. DeSève Laboratory of Biochemical, Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada.
Hamelin
J
J
Gaspar
A M
AM
Day
R
R
Chrétien
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004247:DNA / Q000737:chemistry / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010907:Pituitary Hormones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045664:Proprotein Convertase 1; D043484:Proprotein Convertases; D051381:Rats; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D014018:Tissue Distribution
D015342:DNA Probes; D010907:Pituitary Hormones; D004247:DNA; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1