Identification, analysis, and prediction of protein ubiquitination sites.
Identification, analysis, and prediction of protein ubiquitination sites.
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DOI：
10.1002/prot.22555
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Iakoucheva, Lilia M.
中科院分区：
文献类型：
--
作者：
Radivojac, Predrag;Vacic, Vladimir;Haynes, Chad;Cocklin, Ross R.;Mohan, Amrita;Heyen, Joshua W.;Goebl, Mark G.;Iakoucheva, Lilia M.
关键词：
泛素化在许多细胞过程中起着重要作用，并与许多疾病有关。泛素化位点的实验鉴定是具有挑战性的，因为泛素化蛋白的快速周转和泛素修饰剂的大尺寸。我们确定了141个新的泛素化位点，使用液相色谱，质谱和突变酵母菌株的组合。对已知泛素化位点周围的序列偏好和结构偏好的研究表明，它们的性质与内在无序的蛋白质区域相似。使用一组新的和以前已知的泛素化位点，我们开发了一个随机森林预测的泛素化位点，UbPred。UbPred的类平衡准确率达到72%，ROC曲线下面积为80%。UbPred的应用表明，高置信度的Rsp 5泛素连接酶底物和具有非常短的半衰期的蛋白质在预测的泛素化位点的数量上显著富集。在酿酒酵母中的泛素化位点的蛋白质组范围内的预测表明，高度泛素化的底物中普遍存在的转录/酶调节和参与细胞周期控制的蛋白质。在人类蛋白质组中，细胞骨架蛋白、细胞周期蛋白、调节蛋白和癌症相关蛋白比其他功能类别的蛋白质显示出更高程度的泛素化。我们发现，预测的泛素化位点的获得和丧失可能代表了许多疾病相关突变背后的分子机制。UbPred可在http://www.ubpred.org上获得
Ubiquitination plays an important role in many cellular processes and is implicated in many diseases. Experimental identification of ubiquitination sites is challenging due to rapid turnover of ubiquitinated proteins and the large size of the ubiquitin modifier. We identified 141 new ubiquitination sites using a combination of liquid chromatography, mass spectrometry and mutant yeast strains. Investigation of the sequence biases and structural preferences around known ubiquitination sites indicated that their properties were similar to those of intrinsically disordered protein regions. Using a combined set of new and previously known ubiquitination sites, we developed a random forest predictor of ubiquitination sites, UbPred. The class-balanced accuracy of UbPred reached 72%, with the area under the ROC curve at 80%. The application of UbPred showed that high confidence Rsp5 ubiquitin ligase substrates and proteins with very short half-lives were significantly enriched in the number of predicted ubiquitination sites. Proteome-wide prediction of ubiquitination sites in Saccharomyces cerevisiae indicated that highly ubiquitinated substrates were prevalent among transcription/enzyme regulators and proteins involved in cell cycle control. In the human proteome, cytoskeletal, cell cycle, regulatory and cancer-associated proteins display higher extent of ubiquitination than proteins from other functional categories. We show that gain and loss of predicted ubiquitination sites may likely represent a molecular mechanism behind a number of disease-associated mutations. UbPred is available at http://www.ubpred.org
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影响因子：
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