Genomics and proteomics of vertebrate cholesterol ester lipase (LIPA) and cholesterol 25-hydroxylase (CH25H).

Genomics and proteomics of vertebrate cholesterol ester lipase (LIPA) and cholesterol 25-hydroxylase (CH25H).
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DOI:
10.1007/s13205-011-0013-9
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发表时间:
2011-09
期刊:
影响因子:
2.8
通讯作者:
Cox LA
Cox LA
中科院分区:
工程技术4区
文献类型:
--
作者:
Holmes RS;Vandeberg JL;Cox LA

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胆固醇酯脂肪酶(利帕; EC 3.1.1.13)和胆固醇25-羟化酶(CH 25 H; EC 1.14.99.48)通过水解溶酶体内的胆固醇酯和甘油三酯(利帕)并催化由胆固醇形成25-羟基胆固醇(CH 25 H)(其起到抑制胆固醇生物合成的作用)在体内胆固醇代谢中起重要作用。利用生物信息学方法预测了几种脊椎动物利帕和CH 25 H基因和蛋白的氨基酸序列、结构和基因组特征,并研究了脊椎动物利帕的发生。氨基酸序列比对和预测的亚基结构使得能够识别之前报道的人类利帕和CH 25 H的关键序列以及脊椎动物CH 25 H序列的跨膜结构。脊椎动物利帕和CH 25 H基因在所有脊椎动物基因组中均串联定位,并显示了位于人类基因5′区域内的几个预测的转录因子结合位点和CpG岛。脊椎动物的利帕基因含有9个编码外显子,而所有脊椎动物的CH 25 H基因没有内含子。系统发育分析表明,与其他脊椎动物酸性脂肪酶相比,脊椎动物利帕基因和蛋白质家族具有独特的性质,并且显然是从脊椎动物出现之前的祖先利帕基因进化而来的。本文的在线版本(doi:10.1007/s13205-011-0013-9)包含补充材料,可供授权用户使用。
Cholesterol ester lipase (LIPA; EC 3.1.1.13) and cholesterol 25-hydroxylase (CH25H; EC 1.14.99.48) play essential role in cholesterol metabolism in the body by hydrolysing cholesteryl esters and triglycerides within lysosomes (LIPA) and catalysing the formation of 25-hydroxycholesterol from cholesterol (CH25H) which acts to repress cholesterol biosynthesis. Bioinformatic methods were used to predict the amino acid sequences, structures and genomic features of several vertebrate LIPA and CH25H genes and proteins, and to examine the phylogeny of vertebrate LIPA. Amino acid sequence alignments and predicted subunit structures enabled the identification of key sequences previously reported for human LIPA and CH25H and transmembrane structures for vertebrate CH25H sequences. Vertebrate LIPA and CH25H genes were located in tandem on all vertebrate genomes examined and showed several predicted transcription factor binding sites and CpG islands located within the 5′ regions of the human genes. Vertebrate LIPA genes contained nine coding exons, while all vertebrate CH25H genes were without introns. Phylogenetic analysis demonstrated the distinct nature of the vertebrate LIPA gene and protein family in comparison with other vertebrate acid lipases and has apparently evolved from an ancestral LIPA gene which predated the appearance of vertebrates. The online version of this article (doi:10.1007/s13205-011-0013-9) contains supplementary material, which is available to authorized users.
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