首页> 美国卫生研究院文献>Biochemical Journal >Paralogous murine Nudt10 and Nudt11 genes have differential expression patterns but encode identical proteins that are physiologically competent diphosphoinositol polyphosphate phosphohydrolases.
【2h】

Paralogous murine Nudt10 and Nudt11 genes have differential expression patterns but encode identical proteins that are physiologically competent diphosphoinositol polyphosphate phosphohydrolases.

机译:旁系鼠Nudt10和Nudt11基因具有差异表达模式但编码具有相同生理功能的二磷酸肌醇多磷酸磷酸水解酶。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

We previously described paralogous human genes [NUDT10 and NUDT11 [where NUDT is (nucleoside diphosphate attached moiety 'X')-type motif, also known as the 'nudix'-type motif]] encoding type 3 diphosphoinositol polyphosphate phosphohydrolases (DIPP3) [Hidaka, Caffrey, Hua, Zhang, Falck, Nickel, Carrel, Barnes and Shears (2002) J. Biol. Chem. 277, 32730-32738]. Normally, gene duplication is redundant, and lacks biological significance. Is this true for the DIPP3 genes? We address this question by characterizing highly-conserved murine Nudt10 and Nudt11 homologues of the human genes. Thus these genes must have been duplicated prior to the divergence of primates and sciurognath rodents, approx. 115 million years ago, greatly exceeding the 4 million year half-life for inactivation of redundant paralogues; our data therefore indicate that the DIPP3 duplication is unusual in being physiologically significant. One possible functional consequence is gene neofunctionalization, but we exclude that, since Nudt10 and Nudt11 encode identical proteins. Another possibility is gene subfunctionalization, which we studied by conducting the first quantitative expression analysis of these genes. We demonstrated high Nudt10 expression in liver, kidney and testis; Nudt11 expression is primarily restricted to the brain. This differential, but complementary, expression pattern indicates that subfunctionalization is the evolutionary consequence of DIPP3 gene duplication. Our kinetic data argue that diphosphoinositol polyphosphates are more physiologically relevant substrates for DIPP3 than are either diadenosine hexaphosphate or 5-phosphoribosyl 1-pyrophosphate. Thus the significance of the Nudt10/Nudt11 duplication is specific hydrolysis of diphosphoinositol polyphosphates in a tissue-dependent manner.
机译:先前我们描述了编码3型二磷酸肌醇多磷酸磷酸酶(DIPP3)的旁系人类基因[NUDT10和NUDT11 [其中NUDT是(核苷二磷酸连接的部分'X')型基序,也称为'nudix'型基序]]。 ,Caffrey,Hua,Zhang,Falck,Nickel,Carrel,Barnes和Shears(2002)J.化学277,32730-32738]。通常,基因重复是多余的,并且缺乏生物学意义。 DIPP3基因是真的吗?我们通过表征人类基因的高度保守的鼠Nudt10和Nudt11同源物来解决这个问题。因此,这些基因必须在灵长类动物和Sciurognath啮齿动物发散之前被复制。 1.15亿年前,灭活了多余的旁白,大大超过了400万年的半衰期;因此,我们的数据表明DIPP3复制在生理意义上是不寻常的。一种可能的功能后果是基因新功能化,但我们将其排除在外,因为Nudt10和Nudt11编码相同的蛋白质。另一个可能性是基因亚功能化,我们通过对这些基因进行首次定量表达分析来研究该功能。我们证明了Nudt10在肝,肾和睾丸中的高表达; Nudt11表达主要限于大脑。这种差异但互补的表达模式表明,亚功能化是DIPP3基因复制的进化结果。我们的动力学数据认为,二磷酸肌醇多磷酸酯比六磷酸腺苷六磷酸或5-磷酸核糖基1-焦磷酸酯更适合DIPP3的生理相关底物。因此,Nudt10 / Nudt11复制的意义在于以组织依赖性方式特异性水解二磷酸肌醇多磷酸盐。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号