STRUCTURE OF HUMAN STEROID 21-HYDROXYLASE GENES
STRUCTURE OF HUMAN STEROID 21-HYDROXYLASE GENES
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DOI：
10.1073/pnas.83.14.5111
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发表时间：
1986-07-01
影响因子：
11.1
通讯作者：
DUPONT, B
中科院分区：
文献类型：
--
作者：
WHITE, PC;NEW, MI;DUPONT, B
我们已经确定了编码类固醇21-羟化酶[21-OHase;类固醇21-单加氧酶;类固醇，氢供体：氧氧化还原酶（21-羟基化）; EC 1.14.99.10]的cDNA和两个基因组基因的结构。如果这种细胞色素P-450酶有缺陷，皮质醇不能合成，导致先天性肾上腺皮质增生。编码该酶的cDNA长度为2.0个酶，预测编码的蛋白质含有494个氨基酸残基，分子量为55，000。该酶与已研究的其他P-450酶的同源性最多为28%。21-OH酶基因组基因位于6号染色体上的HLA主要组织相容性复合体中，每个基因包含10个外显子。这种结构不同于其他特征性的P-450基因，其包含7或9个外显子。对21-OHase A或B基因纯合缺失个体的研究表明，只有B基因编码活性酶。这通过以下发现得到证实：A基因在密码子110-112内具有8个碱基缺失，导致移码，将终止密码子带入密码子130处的阅读框。第二个移码和无义突变发生在下游。相反，B基因的外显子序列与cDNA序列相同。因此，21-OHase A基因是假基因。
We have determined the structure of cDNA and two genomic genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10]. If this cytochrome P-450 enzyme is defective, cortisol cannot be synthesized, resulting in congenital adrenal hyperplasia. The cDNA encoding this enzyme is 2.0 kilobases long, and the encoded protein is predicted to contain 494 amino acid residues with a molecular weight of 55,000. This enzyme is at most 28% homologous to other P-450 enzymes that have been studied. The 21-OHase genomic genes, which are located in the HLA major histocompatibiity complex on chromosome 6, each contain 10 exons. This structure is distinct from other characterized P-450 genes, which contain 7 or 9 exons. Studies of individuals with homozygous deletions of the 21-OHase A or B genes suggest that only the B gene encodes an active enzyme. This is confirmed by the finding that the A gene has an 8-base deletion within codons 110-112, resulting in a frameshift that brings a stop codon into the reading frame at codon 130. A second frameshift and a nonsense mutation occur downstream. In contrast, the sequence of the exons of the B gene is identical to the cDNA sequence. The 21-OHase A gene is, therefore, a pseudogene.