GENE STRUCTURE OF HUMAN CYTOCHROME-P-450(SCC), CHOLESTEROL DESMOLASE
GENE STRUCTURE OF HUMAN CYTOCHROME-P-450(SCC), CHOLESTEROL DESMOLASE
复制标题
DOI：
10.1093/oxfordjournals.jbchem.a121955
复制
发表时间：
1987-04-01
影响因子：
2.7
通讯作者：
FUJIIKURIYAMA, Y
中科院分区：
文献类型：
--
作者：
MOROHASHI, K;SOGAWA, K;FUJIIKURIYAMA, Y
以牛P-450(SCC) cDNA为探针，从人类基因组文库中分离到4个含有部分胆固醇脱molase基因的独立克隆。这些克隆覆盖了除第1内含子部分外的整个P-450（SCC）基因。该基因至少20 kb长，由8个内含子分成9个外显子。序列分析表明，9个分离的外显子编码了一个由521个氨基酸组成的一级结构，与牛P-450（SCC）具有72%的同源性。CATT序列和TATAAT序列分别位于起始密码子上游129和91 bp处，可能是一个“CAT”盒和一个“TATA”盒。在该基因的第6个内含子中发现了以GC开头的不寻常的外显子/内含子连接序列。通过与牛P-450（SCC）序列的比较，在人P-450（SCC）序列中发现了一个由39个氨基酸组成的推定延伸肽。在这两种形式的P-450（SCC）的延伸肽中发现了两个保守区域，提示该部分在P-450（SCC）前体的线粒体定位和加工中起功能作用。成熟的人P-450（SCC）只有一个半胱氨酸残基，位于HR2区域的中心（Gotoh et al. (1983) J. Biochem, 97, 807-817）。这一观察结果毫无疑问地证实了HR2区唯一的半胱氨酸残基是血红素的第5配体。
Four indpendent clones containing a part of the P-450(SCC), cholesterol desmolase, gene were isolated from human genomic libraries using bovine P-450(SCC) cDNA as a probe. These clones covered the entire P-450(SCC) gene except for a part of the 1st intron. The gene is at least 20 kb long and is split into 9 exons by 8 introns. The sequence analysis revealed that the nine separated exons code for a primary structure consisting of 521 amino acids which shows 72% homology with that of bovine P-450(SCC). A CATT sequence and a TATAAT sequence, which are possibly a "CAT" box, and a "TATA" box, respectively, are present 129 and 91 bp upstream from the initiation codon. An unusual exon/intron junctional sequence that begins with GC was found in the 6th intron of the gene. A putative extension peptide consisting of 39 amino acids was found in the sequence of human P-450(SCC) by comparison with that of the bovine counterpart. Two conserved regions were found in the extension peptide of these two forms of P-450(SCC), suggesting a functional role of the portions in the mitochondrial localization and processing of P-450(SCC) precursor. The mature form of human P-450(SCC) has only one cysteine residue, which was located in the center of the HR2 region (Gotoh et al. (1983) J. Biochem, 97, 807-817). This observation established beyond doubt that the sole cysteine residue in the HR2 region is the 5th ligand to the heme.