Mornet E, Dupont J, Vitek A, White P C
Division of Pediatric Endocrinology, Cornell University Medical College, New York, New York 10021.
J Biol Chem. 1989 Dec 15;264(35):20961-7.
Steroid 11 beta-hydroxylase (P-450(11) beta) is a mitochondrial cytochrome P-450 enzyme necessary for cortisol biosynthesis. Deficiency of 11 beta-hydroxylase causes a hypertensive form of congenital adrenal hyperplasia. A partial cDNA clone encoding this enzyme has been previously isolated and the corresponding gene, CYP11B1, mapped to human chromosome 8q. This gene has now been isolated along with a second linked homologous gene, CYP11B2. Each gene contains nine exons. The eight introns are identical in location to the introns of the CYP11A gene encoding another mitochondrial P-450 enzyme, cholesterol desmolase, confirming that 11 beta-hydroxylase and cholesterol desmolase are in the same gene family within the P-450 superfamily. The nucleotide sequences of CYP11B1 and B2 are 95% identical in coding regions and about 90% identical in introns. The putative proteins encoded by CYP11B1 and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identical to the predicted sequence of bovine P-450(11) beta. There are no obviously deleterious mutations in coding sequences of CYP11B2. However, the 5'-flanking regions of CYP11B1 and B2 have diverged considerably, and B2 transcripts were not detected in human adrenal mRNA or among cDNA clones.
类固醇11β-羟化酶（P-450(11)β）是皮质醇生物合成所必需的一种线粒体细胞色素P-450酶。11β-羟化酶缺乏会导致一种高血压型先天性肾上腺增生症。先前已分离出编码该酶的部分cDNA克隆，其相应基因CYP11B1定位于人类染色体8q。现在，该基因已与另一个连锁的同源基因CYP11B2一起被分离出来。每个基因都包含9个外显子。8个内含子的位置与编码另一种线粒体P-450酶胆固醇侧链裂解酶的CYP11A基因的内含子相同，这证实了11β-羟化酶和胆固醇侧链裂解酶属于P-450超家族中的同一个基因家族。CYP11B1和B2的核苷酸序列在编码区有95%相同，在内含子中有约90%相同。由CYP11B1和B2编码的推定蛋白质各自包含503个氨基酸，包括一个24个残基的信号肽，并且它们的序列彼此有93%相同，与牛P-450(11)β的预测序列有75%相同。CYP11B2的编码序列中没有明显的有害突变。然而，CYP11B1和B2的5'侧翼区域有很大差异，在人肾上腺mRNA或cDNA克隆中未检测到B2转录本。
