Loss of post-translational modification sites in disease.
Loss of post-translational modification sites in disease.
复制标题
疾病中翻译后修饰位点的丢失。
DOI：
10.1142/9789814295291_0036
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发表时间：
2010
影响因子：
--
通讯作者：
Radivojac,Predrag
中科院分区：
文献类型：
--
作者：
Li,Shuyan;Iakoucheva,LiliaM;Mooney,SeanD;Radivojac,Predrag
了解和预测疾病的分子病因是生物学和医学的主要挑战之一。一个特别感兴趣的领域仍然是疾病相关的氨基酸取代的计算分析。为此，已经进行了各种研究以鉴定被致病突变破坏的分子功能。在这里，我们研究了疾病相关突变对翻译后修饰的影响。特别是，我们研究了疾病突变导致的修饰靶位点的丢失。我们发现，大约5%的疾病相关突变可能会影响已知的修饰位点，部分（4%）或完全（1%），而推定的中性多态性约为2%。分析的15种翻译后修饰类型中的大多数被发现偶然地以高于预期的水平被破坏。还将疾病突变位点的分子功能和理化性质与参与翻译后修饰位点破坏过程的中性多态性进行了比较。疾病相关的突变后的修饰位点附近被发现是丰富的突变，改变野生型氨基酸的极性，电荷和疏水性。总体而言，这些结果进一步表明，修饰位点的破坏是人类遗传疾病的重要但不是主要原因。
Understanding and predicting molecular cause of disease is one of the major challenges for biology and medicine. One particular area of interest continues to be computational analyses of disease-associated amino acid substitutions. To this end, various studies have been performed to identify molecular functions disrupted by disease-causing mutations. Here, we investigate the influence of disease-associated mutations on post-translational modifications. In particular, we study the loss of modification target sites as a consequence of disease mutation. We find that about 5% of disease-associated mutations may affect known modification sites, either partially (4%) of fully (1%), compared to about 2% of putatively neutral polymorphisms. Most of the fifteen post-translational modification types analyzed were found to be disrupted at levels higher than expected by chance. Molecular functions and physiochemical properties at sites of disease mutation were also compared to those of neutral polymorphisms involved in the process of post-translational modification site disruption. Disease-associated mutations in the neighborhood of post-translationally modified sites were found to be enriched in mutations that change polarity, charge, and hydrophobicity of the wild-type amino acids. Overall, these results further suggest that disruption of modification sites is an important but not the major cause of human genetic disease.