Dusetti N J, Frigerio J M, Keim V, Dagorn J C, Iovanna J L
U.315 Institut National de la Santé et de la Recherche Médicale, Marseille, France.
J Biol Chem. 1993 Jul 5;268(19):14470-5.
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.
大鼠胰腺炎相关蛋白（PAP）mRNA在正常胰腺中几乎检测不到，但在急性胰腺炎期间会过度表达（约万纳，J.，奥雷勒，B.，凯姆，V.，和达戈尔恩J.-C.（1991年）《生物化学杂志》266卷，24664 - 24669页）。通过逆转录酶偶联聚合酶链反应进行的RNA扩增表明，PAP mRNA在十二指肠、空肠和回肠中组成性表达，在胰腺炎急性期的表达水平与胰腺相似。在其他几个组织中也检测到了微弱表达。从基因组文库中分离出大鼠PAP基因，并对超过3.2千碱基的基因序列和1.2千碱基的5'侧翼序列进行了表征。通过PAP转录本的引物延伸确定了编码序列的5'末端。在启动子区域鉴定出了几个潜在的调控元件，包括一个胰腺特异性共有序列、两个Pan1（胰腺特异性）转录激活因子、两个IL - 6反应元件和一个糖皮质激素反应元件。PAP编码序列跨越六个外显子。前三个外显子分别编码mRNA的5'非翻译区、信号肽和成熟蛋白NH2末端的39个氨基酸。其他三个外显子编码与动物凝集素的碳水化合物识别结构域具有显著同源性的蛋白质结构域。将PAP基因与13个含碳水化合物识别结构域的基因进行序列比较，发现它们源自同一个祖先基因。然而，碳水化合物识别结构域内内含子的位置不同，这表明PAP属于一类新的凝集素。这些结果支持了这样一种假说，即编码PAP和其他凝集素的基因是通过内含子获得从一个共同的祖先基因进化而来的。
