Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta).
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.
Mornet
E
E
Division of Pediatric Endocrinology, Cornell University Medical College, New York, New York 10021.
Dupont
J
J
Vitek
A
A
White
P C
PC
D000311:Adrenal Glands / Q000201:enzymology; D000595:Amino Acid Sequence; D001483:Base Sequence; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D003062:Codon / Q000235:genetics; D005091:Exons; D005796:Genes; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D011544:Pseudogenes; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
D003062:Codon; D015345:Oligonucleotide Probes; D013250:Steroid Hydroxylases; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme