Genomics and evolution of protein phosphatases
Genomics and evolution of protein phosphatases
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DOI：
10.1126/scisignal.aag1796
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发表时间：
2017-04-11
影响因子：
7.3
通讯作者：
Manning, Gerard
中科院分区：
文献类型：
--
作者：
Chen, Mark J.;Dixon, Jack E.;Manning, Gerard
蛋白磷酸酶是蛋白激酶的基本对立面;这些酶一起调节所有蛋白磷酸化和大多数细胞过程。为了更好地理解蛋白磷酸化的全局作用，我们对由189个已知和预测的人类蛋白磷酸酶基因组成的人类蛋白磷酸酶组进行了编目。我们还鉴定了79个蛋白磷酸酶假基因或逆转录基因，其中一些可能具有残留功能。我们追踪磷酸酶的起源和多样性，通过构建其他八种真核生物的蛋白质磷酸酶，从原生生物网柄藻到海胆。我们从所有9个物种的蛋白磷酸酶分为10个蛋白折叠，21个家庭，和178个亚科的层次。我们发现，在101个人类亚家族中，超过80%的亚家族在动物界中是保守的，但在进化中表现出了实质性的差异，包括单个亚家族的丢失和扩展以及附属结构域的变化。蛋白磷酸酶显示出与激酶相似的进化动力学，在主要的模式生物中有大量的损失。序列分析预测，26个人类蛋白磷酸酶结构域是催化失能的，并且这种失能在直系同源物中大多是保守的。蛋白磷酸酶的基因组和进化的角度提供了一个框架，全球分析整个动物王国的蛋白磷酸化。
Protein phosphatases are the essential opposite to protein kinases; together, these enzymes regulate all protein phosphorylation and most cellular processes. To better understand the global roles of protein phosphorylation, we cataloged the human protein phosphatome, composed of 189 known and predicted human protein phosphatase genes. We also identified 79 protein phosphatase pseudogenes or retrogenes, some of which may have residual function. We traced the origin and diversity of phosphatases by building protein phosphatomes for eight other eukaryotes, from the protist Dictyostelium to the sea urchin. We classified protein phosphatases from all nine species into a hierarchy of 10 protein folds, 21 families, and 178 subfamilies. We found that >80% of the 101 human subfamilies were conserved across the animal kingdom, but show substantial differences in evolution, including losses and expansions of individual subfamilies and changes in accessory domains. Protein phosphatases show similar evolutionary dynamics to those of kinases, with substantial losses in major model organisms. Sequence analysis predicts that 26 human protein phosphatase domains are catalytically disabled and that this disability is mostly conserved across orthologs. This genomic and evolutionary perspective on protein phosphatases provides a framework for global analysis of protein phosphorylation throughout the animal kingdom.