Exons of the human pancreatic polypeptide gene define functional domains of the precursor.
Pancreatic polypeptide is a 36-amino acid peptide which inhibits pancreatic exocrine function. We have previously determined from the nucleotide sequence of a cDNA that pancreatic polypeptide is derived from a 95-amino acid precursor, prepropancreatic polypeptide. Pulse-chase studies have suggested that the precursor is cleaved to produce three peptides: pancreatic polypeptide, an icosapeptide, and a smaller peptide. In the present study, we have used the cloned cDNA as a hybridization probe to isolate the pancreatic polypeptide gene from a human bacteriophage genomic library. The nucleotide sequence of 2.8 kilobases of DNA representing the entire human pancreatic polypeptide gene was determined. The gene contains four exons and three introns. Exon 1 encodes the 5'-untranslated region of the mRNA, exon 2 encodes the signal sequence and the sequence of pancreatic polypeptide, exon 3 encodes the icosapeptide, and exon 4 encodes a carboxyl-terminal heptapeptide and the 3'-untranslated region of the mRNA. By Southern blot analysis, the gene detected in a pancreatic polypeptide-producing islet cell tumor was indistinguishable from that in normal human leukocytes. The structure of the human pancreatic polypeptide gene is consistent with the hypothesis that prepropancreatic polypeptide generates three distinct peptides, each encoded by a separate exon. Increased expression of pancreatic polypeptide in the islet cell tumor does not appear to be correlated with major alterations in pancreatic polypeptide gene structure.
D007516:Adenoma, Islet Cell / Q000235:genetics; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004274:DNA, Recombinant; D006801:Humans; D009693:Nucleic Acid Hybridization; D010191:Pancreatic Polypeptide / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D004274:DNA, Recombinant; C043710:PPY protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D010191:Pancreatic Polypeptide; D004247:DNA; D004262:DNA Restriction Enzymes