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秀丽隐杆线虫长寿基因clk-1在小鼠和人类中的直系同源基因。

Orthologues of the Caenorhabditis elegans longevity gene clk-1 in mouse and human.

作者信息

Asaumi S, Kuroyanagi H, Seki N, Shirasawa T

机构信息

Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

出版信息

Genomics. 1999 Jun 15;58(3):293-301. doi: 10.1006/geno.1999.5838.

Abstract

The clk-1 gene was isolated from the long-lived mutant of Caenorhabditis elegans and was suggested to play a biological role in longevity (Ewbank et al., 1997, Science 275: 980-983). The primary structure of CLK-1 showed a significant homology to Saccharomyces cerevisiae Coq7p/Cat5p, which is required for the biosynthesis of ubiquinone and the derepression of gluconeogenic genes. In the present study, we isolated and characterized human and mouse orthologues of the COQ7/CLK-1 gene. Sequence analysis of both the human and the mouse COQ7 cDNAs showed an open reading frame composed of 217 amino acids with calculated molecular mass of 24,309 and 24,044 Da, respectively. Homology search revealed that human COQ7 showed 85% identity to mouse COQ7, 89% identity to rat COQ7, 53% identity to C. elegans CLK-1, and 37% identity to S. cerevisiae Coq7p/Cat5p. Zoo blot analysis implied that the COQ7 gene was well conserved among mammal, bird, and reptile genomes. Tissue blot analysis showed that human COQ7 is dominantly transcribed in heart and skeletal muscle. Genomic analyses revealed that the human COQ7 gene is composed of six exons spanning 11 kb of human genome as a single-copy gene. Radiation hybrid mapping assigned the COQ7 gene to human chromosome 16p12.3-p13.11.

摘要

clk-1基因是从秀丽隐杆线虫的长寿突变体中分离出来的,据推测它在寿命方面发挥着生物学作用(Ewbank等人,1997年,《科学》275卷:980 - 983页)。CLK-1的一级结构与酿酒酵母的Coq7p/Cat5p显示出显著的同源性,Coq7p/Cat5p是泛醌生物合成和糖异生基因去阻遏所必需的。在本研究中,我们分离并鉴定了COQ7/CLK-1基因的人类和小鼠直系同源物。对人类和小鼠COQ7 cDNA的序列分析显示,其开放阅读框由217个氨基酸组成,计算得到的分子量分别为24,309和24,044道尔顿。同源性搜索表明,人类COQ7与小鼠COQ7的同一性为85%,与大鼠COQ7的同一性为89%,与秀丽隐杆线虫CLK-1的同一性为53%,与酿酒酵母Coq7p/Cat5p的同一性为37%。动物杂交印迹分析表明,COQ7基因在哺乳动物、鸟类和爬行动物基因组中高度保守。组织印迹分析显示,人类COQ7在心脏和骨骼肌中主要转录。基因组分析表明,人类COQ7基因由六个外显子组成,跨越人类基因组的11 kb,为单拷贝基因。辐射杂种图谱分析将COQ7基因定位到人类染色体16p12.3 - p13.11。

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