Blake-Palmer Katherine G, Su Ya, Smith Annabel N, Karet Fiona E
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
Gene. 2007 May 15;393(1-2):94-100. doi: 10.1016/j.gene.2007.01.020. Epub 2007 Feb 7.
Several of the 13 subunits comprising mammalian H(+)-ATPases have multiple alternative forms, encoded by separate genes and with differing tissue expression patterns. These may play an important role in the intracellular localization and activity of H(+)-ATPases. Here we report the cloning of a previously uncharacterized human gene, ATP6V0E2, encoding a novel H(+)-ATPase e-subunit designated e2. We demonstrate that in contrast to the ubiquitously expressed gene encoding the e1 subunit (previously called e), this novel gene is expressed in a more restricted tissue distribution, particularly kidney and brain. We show by complementation studies in a yeast strain deficient for the ortholog of this subunit, that either form of the e-subunit is essential for proper proton pump function. The identification of this novel form of the e-subunit lends further support to the hypothesis that subunit differences may play a key role in the structure, site and function of H(+)-ATPases within the cell.
构成哺乳动物H(+)-ATP酶的13个亚基中有几个具有多种可变形式，由不同基因编码且具有不同的组织表达模式。这些可变形式可能在H(+)-ATP酶的细胞内定位和活性中发挥重要作用。在此，我们报告了一个先前未被鉴定的人类基因ATP6V0E2的克隆，该基因编码一种名为e2的新型H(+)-ATP酶e亚基。我们证明，与编码e1亚基（先前称为e）的普遍表达基因不同，这个新基因的组织分布更为局限，尤其在肾脏和大脑中表达。我们通过在缺乏该亚基直系同源物的酵母菌株中进行互补研究表明，e亚基的任何一种形式对于质子泵的正常功能都是必不可少的。这种新型e亚基的鉴定进一步支持了亚基差异可能在细胞内H(+)-ATP酶的结构、定位和功能中起关键作用这一假说。
