Structural organization of the gene encoding the rat pancreatitis-associated protein. Analysis of its evolutionary history reveals an ancient divergence from the other carbohydrate-recognition domain-containing genes.
Rat pancreatitis-associated protein (PAP) mRNA is barely detectable in normal pancreas and overexpressed during acute pancreatitis (Iovanna, J., Orelle, B., Keim, V., and Dagorn J.-C. (1991) J. Biol. Chem. 266, 24664-24669). RNA amplification by reverse-transcriptase-coupled polymerase chain reaction showed that PAP mRNA was constitutively expressed in duodenum, jejunum, and ileum, at similar levels as in pancreas during the acute phase of pancreatitis. A weak expression was also detected in several other tissues. The rat PAP gene was isolated from a genomic library and characterized over 3.2 kilobases of gene sequence and 1.2 kilobases of 5'-flanking sequence. The 5' end of the coding sequence was determined by primer extension of the PAP transcript. Several potential regulatory elements were identified in the promoter region, including a pancreas-specific consensus sequence, two Pan1 (pancreas-specific) transcription activators, two IL-6 response elements, and one glucocorticoid response element. The PAP coding sequence spanned over six exons. The first three exons encoded the 5'-untranslated region of the mRNA, the signal peptide, and 39 amino acids of the NH2-terminal end of the mature protein, respectively. The other three exons encoded a domain of the protein with significant homology to the carbohydrate-recognition domain of animal lectins. Sequence comparison of the PAP gene with 13 carbohydrate-recognition domain-containing genes revealed that they derived from the same ancestor gene. Position of introns within the carbohydrate-recognition domain were different, however, suggesting that PAP belongs to a new group of lectins. These results support the hypothesis that genes encoding PAP and other lectins evolved from a common ancestor gene by intron gain.
Dusetti
N J
NJ
U.315 Institut National de la Santé et de la Recherche Médicale, Marseille, France.
Frigerio
J M
JM
Keim
V
V
Dagorn
J C
JC
Iovanna
J L
JL
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D001483:Base Sequence; D005075:Biological Evolution; D014408:Biomarkers, Tumor; D005091:Exons; D015870:Gene Expression; D014644:Genetic Variation; D007438:Introns; D037102:Lectins / Q000235:genetics*; D037181:Lectins, C-Type; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D010195:Pancreatitis / Q000235:genetics*; D000073718:Pancreatitis-Associated Proteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037102:Lectins; D037181:Lectins, C-Type; D016376:Oligonucleotides, Antisense; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C000612144:Reg3b protein, rat