Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P450c17 is the single enzyme mediating both 17 alpha-hydroxylase (steroid 17 alpha-monooxygenase, EC 1.14.99.9) and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. We sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, lambda hac17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17. Comparison of the amino acid sequence of P450c17 with two other human steroidogenic cytochromes P450 show much greater homology with P450c21 (28.9%), another microsomal enzyme, than with P450scc (12.3%), a mitochondrial enzyme.
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PMID:Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. 302 70

P450c17 is a single cytochrome P450 enzyme mediating both 17 alpha-hydroxylase and 17,20 lyase activities in the biosynthesis of steroid hormones. We have cloned and sequenced the human P450XVIIA1 gene lying on chromosome 10, which encodes P450c17. The gene spans 6569 bp and is divided into eight exons by seven introns. This intron/exon structure closely resembles that of the P450XXI genes encoding P450c21 (steroid 21-hydroxylase), which contain 10 exons, except that the introns dividing exons 1 and 2 and exons 4 and 5 in the P450XXI gene are absent in the P450XVII gene. Furthermore, computer modeling studies indicate the conformations of P450c17 and P450c21 are very similar. The structures of the P450XXVII and P450XXI genes are very different from other classes of P450 genes. Although the production of P450c17 is under different hormonal, ontogenic, and tissue-specific controls in various types of steroidogenic cells, the adrenal and testis transcribe the P450XVIIA1 gene into P450c17 mRNAs having the same cap sites. S1 nuclease protection experiments locate the principal cap sites as a G residue lying 22 bases 3' to an atypical TTTAAA promoter, and 82 bases 3' to a typical CAAT box. The 5'-flanking DNA contains sequences similar to consensus sequences regulated by cAMP and glucocorticoids.
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PMID:Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. 350 22