Mammalian carboxylesterase 3: comparative genomics and proteomics.

Mammalian carboxylesterase 3: comparative genomics and proteomics.
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DOI:
10.1007/s10709-010-9438-z
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发表时间:
2010-07
期刊:
影响因子:
1.5
通讯作者:
VandeBerg, John L.
VandeBerg, John L.
中科院分区:
生物学4区
文献类型:
--
作者:
Holmes, Roger S.;Cox, Laura A.;VandeBerg, John L.

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哺乳动物羧酸酯酶(CES)至少有五个家族催化多种药物和外源性物质的水解或酯交换,也可能参与脂肪酰基和胆固醇酯代谢。在这项研究中,计算机模拟方法被用来预测氨基酸序列,二级和三级结构,基因位置的CES3基因和编码的蛋白质使用的数据从几个哺乳动物基因组计划。哺乳动物CES3基因与CES2和CES6基因位于CES基因簇内,通常包含转录在正DNA链上的13个外显子。有证据表明黑猩猩和小鼠基因组中存在重复的CES3基因。哺乳动物CES3蛋白亚基共有58 - 97%的序列同一性,并表现出关键CES氨基酸残基的序列比对和同一性,以及预测的二级和三级结构与先前报道的人CES1的保守性。人类基因组计划先前已经报道了CES3 mRNA同种型在几种组织中的表达,特别是在结肠、气管和脑中。预测的人CES3同工蛋白显然来源于外显子改组,并且可能分泌到细胞外或保留在细胞质内。小鼠CES3样转录物定位于小鼠大脑的特定区域,包括小脑,并且可能在神经组织和身体其他组织中的药物和外源性物质的解毒中发挥作用。系统发育分析表明,哺乳动物CES3基因家族与其他哺乳动物CES基因家族相关但又不同,它们之间的关系和潜在的进化起源。
At least five families of mammalian carboxylesterases (CES) catalyse the hydrolysis or transesterification of a wide range of drugs and xenobiotics and may also participate in fatty acyl and cholesterol ester metabolism. In this study, in silico methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for CES3 genes and encoded proteins using data from several mammalian genome projects. Mammalian CES3 genes were located within a CES gene cluster with CES2 and CES6 genes, usually containing 13 exons transcribed on the positive DNA strand. Evidence is reported for duplicated CES3 genes for the chimp and mouse genomes. Mammalian CES3 protein subunits shared 58–97% sequence identity and exhibited sequence alignments and identities for key CES amino acid residues as well as extensive conservation of predicted secondary and tertiary structures with those previously reported for human CES1. The human genome project has previously reported CES3 mRNA isoform expression in several tissues, particularly in colon, trachea and in brain. Predicted human CES3 isoproteins were apparently derived from exon shuffling and are likely to be secreted extracellularly or retained within the cytoplasm. Mouse CES3-like transcripts were localized in specific regions of the mouse brain, including the cerebellum, and may play a role in the detoxification of drugs and xenobiotics in neural tissues and other tissues of the body. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the mammalian CES3 family of genes which were related to but distinct from other mammalian CES gene families.
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