Tasanen K, Parkkonen T, Chow L T, Kivirikko K I, Pihlajaniemi T
Biocenter, University of Oulu, Finland.
J Biol Chem. 1988 Nov 5;263(31):16218-24.
A single polypeptide acts as the beta subunit of prolyl 4-hydroxylase and the enzyme protein disulfide isomerase and may also function as a cellular thyroid hormone binding protein. We report here that the human gene for this polypeptide is about 18 kilobase pairs and consists of 11 exons. The two thioredoxin-like regions are coded by exons 1-2 and 8-9, respectively. The codons for the two presumed active sites of protein disulfide isomerase, each a Cys-Gly-His-Cys sequence, are located 12 base pairs from the beginning of exons 2 and 9. The last 3 amino acids coded by exons 1 and 8 and the first 9 amino acids coded by exons 2 and 9, including a broken codon for Tyr, are identical in the respective exon-intron junctions. These regions are also highly homologous to the active sites of bacterial thioredoxins. The data suggest that evolution of this gene has involved exon shuffling and duplication of a two-exon unit, in which the internal exon-intron junctions have been entirely conserved. The region between exons 1-2 and 8-9 appears to contain other duplications. The 5' flanking sequences contain a TATA box, six CCAAT boxes, and other elements which may be involved in regulation of the cellular amounts of this polypeptide.
一种单一的多肽充当脯氨酰4-羟化酶的β亚基和酶蛋白二硫键异构酶，并且可能还作为一种细胞甲状腺激素结合蛋白发挥作用。我们在此报告，该多肽的人类基因约为18千碱基对，由11个外显子组成。两个硫氧还蛋白样区域分别由外显子1 - 2和8 - 9编码。蛋白二硫键异构酶的两个假定活性位点的密码子，每个都是Cys - Gly - His - Cys序列，位于外显子2和9起始处的12个碱基对处。由外显子1和8编码的最后3个氨基酸以及由外显子2和9编码的前9个氨基酸，包括一个酪氨酸的间断密码子，在各自的外显子 - 内含子连接处是相同的。这些区域也与细菌硫氧还蛋白的活性位点高度同源。数据表明，该基因的进化涉及一个两外显子单元的外显子重排和复制，其中内部的外显子 - 内含子连接处完全保守。外显子1 - 2和8 - 9之间的区域似乎包含其他重复序列。5'侧翼序列包含一个TATA盒、六个CCAAT盒以及其他可能参与调节该多肽细胞含量的元件。
