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COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta).
Journal of Biological Chemistry 1989 December 16
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.
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