The human glutamate dehydrogenase gene family: gene organization and structural characterization.
The human glutamate dehydrogenase gene family: gene organization and structural characterization.
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DOI：
10.1006/geno.1993.1152
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发表时间：
1993-04
期刊：
影响因子：
4.4
通讯作者：
T. Michaelidis;G. Tzimagiorgis;N. Moschonas;J. Papamatheakis
中科院分区：
文献类型：
--
作者：
T. Michaelidis;G. Tzimagiorgis;N. Moschonas;J. Papamatheakis
谷氨酸脱氢酶是一种位于线粒体的关键代谢酶。除了一般的代谢作用外，GLUD在神经传递中也很重要。GLUD酶活性的显著改变与某些神经退行性人类疾病有关。虽然目前只鉴定出一种人类GLUD cDNA分子，但基因组DNA Southern和细胞遗传学分析都表明GLUD基因家族的存在。用GLUD cDNA筛选人类基因组lambda-噬菌体文库，使我们分离出几个克隆，分为五个结构不同的contigs。我们已经通过详细的基因组南方分析证实了人类基因组中所有glud特异性序列的存在。本研究鉴定了GLUD的完整功能基因，命名为GLUD1。GLUD1基因长约45kb，由13个外显子组成。确定其核苷酸序列、外显子-内含子边界和转录起始位点。Sp1、AP-1和AP-2等多种调控因子的潜在结合位点在该基因的启动子区域被识别出来。其他组的成员表现出与GLUD1明显不同的组织结构。两个不同的glud特异性基因位点，称为GLUDP2和GLUDP3，可能代表截断的假基因。它们与GLUD1的高度相似性仅限于外显子2、3和4周围的区域。最后，另外两个GLUD特异性基因组序列，称为GLUDP4和GLUDP5，在结构上与GLUD cDNA序列的3'部分相似。这些位点可能代表由反转录转位产生的gld假基因的截短。这里提供的数据表明，所有的人类GLUD假基因最近在进化中出现了分化。
Glutamate dehydrogenase is a mitochondrially located, key metabolic enzyme. In addition to its general metabolic role, GLUD is important in neurotransmission. Significant alterations in GLUD enzymatic activity have been associated with certain neurodegenerative human disorders. Although a single species of human GLUD cDNA molecule has been identified so far, both genomic DNA Southern and cytogenetic analyses have indicated the presence of a GLUD gene family. Screening of a human genomic lambda-phage library with the GLUD cDNA, led us to the isolation of several clones divided into five structurally distinct contigs. We have confirmed the presence of all GLUD-specific sequences in the human genome by detailed genomic Southern analysis. This study allowed the identification of the entire functional GLUD gene, named GLUD1. The GLUD1 gene is about 45 kb long and it is organized into 13 exons. Its nucleotide sequence, exon-intron boundaries, and transcription start sites were determined. Potential binding sites for various regulatory factors such as Sp1, AP-1, and AP-2 were recognized at the promoter region of the gene. The members of the other contigs showed an organization clearly different from GLUD1. Two distinct GLUD-specific gene loci, termed GLUDP2 and GLUDP3, possibly represent truncated pseudogenes. Their high degree of similarity to GLUD1 is limited to the region surrounding exons 2, 3, and 4. Finally, two additional GLUD-specific genomic sequences, termed GLUDP4 and GLUDP5, are structurally similar with the 3' part of the GLUD cDNA sequence. These loci probably represent truncated GLUD pseudogenes generated by retrotransposition. The data presented here suggest that all human GLUD pseudogenes have diverged recently in evolution.