Emi Y, Ikushiro S, Iyanagi T
Department of Life Science, Faculty of Science, Himeji Institute of Technology, Harima Science Park City, Hyogo.
J Biochem. 1995 Feb;117(2):392-9. doi: 10.1093/jb/117.2.392.
Genomic clones of UDP-glucuronosyltransferase family 1 (UGT1) were isolated from wild-type Wistar rats. The UGT1 locus spans > 120 kb and forms a gene complex. In this locus nine unique first exons encoding NH2-terminal portions of each isoform were located at intervals of approximately 10 kb and followed by only one set of commonly used exons (exons II, III, IV, and V) encoding the COOH-terminal portion. From sequence analyses of the unique first exons, the amino acid sequences of the isoforms were deduced and they were divided into two groups: the Bilirubin cluster (B cluster) and the Phenol cluster (A cluster). A and B clusters consisted of four (A1-A4) and five (B1-B5) isoform-specific exons, respectively. A2, A3, B3, and B4 were identified as previously uncharacterized forms, while A4 and B4 were pseudogenes. Isoform B1 was a major component in hepatic microsomes of untreated rats and was induced in clofibrate- and dexamethasone-administered rats. A slight but a significant amount of B1 mRNA was also detected in various tissues such as intestine. mRNAs coding for isoform A1 and isoform A2 were induced in livers of methylcholanthrene (MC)-treated rats. Induction of A1 mRNA was also observed in kidneys of MC-treated rats. A genomic clone containing the commonly used exons was also isolated from Gunn rats and a single base deletion was identified in exon IV. Isoforms of the UGT1 family are made from the complex gene locus by an alternative combination of one of the unique first exons with the commonly used exons.
从野生型Wistar大鼠中分离出尿苷二磷酸葡萄糖醛酸基转移酶1（UGT1）家族的基因组克隆。UGT1基因座跨度超过120 kb，形成一个基因复合体。在这个基因座中，九个编码各同工型NH2末端部分的独特的第一外显子以大约10 kb的间隔排列，随后仅跟着一组编码COOH末端部分的常用外显子（外显子II、III、IV和V）。通过对独特的第一外显子的序列分析，推导了同工型的氨基酸序列，并将它们分为两组：胆红素簇（B簇）和苯酚簇（A簇）。A簇和B簇分别由四个（A1 - A4）和五个（B1 - B5）同工型特异性外显子组成。A2、A3、B3和B4被鉴定为以前未表征的形式，而A4和B4是假基因。同工型B1是未处理大鼠肝微粒体中的主要成分，在给予氯贝丁酯和地塞米松的大鼠中被诱导。在诸如肠道等各种组织中也检测到少量但显著量的B1 mRNA。编码同工型A1和同工型A2的mRNA在经甲基胆蒽（MC）处理的大鼠肝脏中被诱导。在经MC处理的大鼠肾脏中也观察到A1 mRNA的诱导。还从Gunn大鼠中分离出一个包含常用外显子的基因组克隆，并在外显子IV中鉴定出一个单碱基缺失。UGT1家族的同工型由该复合基因座通过独特的第一外显子之一与常用外显子的交替组合产生。
