Prediction of peroxisomal targeting signal 1 containing proteins from amino acid sequence
Prediction of peroxisomal targeting signal 1 containing proteins from amino acid sequence
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DOI：
10.1016/s0022-2836(03)00319-x
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发表时间：
2003-05-02
影响因子：
5.6
通讯作者：
Eisenhaber, F
中科院分区：
文献类型：
--
作者：
Neuberger, G;Maurer-Stroh, S;Eisenhaber, F
过氧化物酶体基质蛋白必须在消化后输入到它们的靶细胞器中。主要的易位途径取决于C-末端靶向信号，称为PTS 1。我们先前对PTS 1基序中序列变异性的分析表明，除了已知的C-末端三肽之外，直接上游的至少9个残基对于PTS 1-Pex 5受体复合物中的信号识别是重要的。改进的PTS 1基序描述在由分类群特异性功能（后生动物，真菌，剩余分类群）组成的预测工具中实现，能够识别查询序列中的潜在PTS 1。复合得分函数由经典的配置文件条款和额外的条款处罚从序列段上导出的物理性质模式的偏差。预测算法已被验证的自我一致性和三个不同的交叉验证测试。此外，我们在大量非过氧化物酶体阴性、突变数据上测试了该工具，并将预测率与PSORT 2程序的PTS 1组件进行了比较。我们的预测器在识别记录的包含蛋白质的PTS 1信号方面的灵敏度接近90%，可以进行可靠的预测。预测区分甚至SKL附加的非过氧化物酶体靶向蛋白质，如小鼠二氢叶酸还原酶-SKL构建体。相应的假阳性率不低于0.8%，因此，该工具可以应用于大规模无监督序列数据库注释。对公共蛋白质数据库的扫描发现了一些尚未表征的蛋白质，其中PTS 1信号可能对生物功能至关重要。预测的PTS 1信号的存在意味着在不存在N-末端靶向序列如线粒体输入信号的情况下过氧化物酶体定位。(C)2003爱思唯尔科技有限公司版权所有。
Peroxisomal matrix proteins have to be imported into their target organelle post-translationally. The major translocation pathway depends on a C-terminal targeting signal, termed PTS1. Our previous analysis of sequence variability in the PTS1 motif revealed that, in addition to the known C-terminal tripeptide, at least nine residues directly upstream are important for signal recognition in the PTS1-Pex5 receptor complex. The refined PTS1 motif description was implemented in a prediction tool composed of taxon-specific functions (metazoa, fungi, remaining taxa), capable of recognising potential PTS1s in query sequences. The composite score function consists of classical profile terms and additional terms penalising deviations from the derived physical property pattern over sequence segments. The prediction algorithm has been validated with a self-consistency and three different cross-validation tests. Additionally, we tested the tool on a large set of non-peroxisomal negatives, on mutation data, and compared the prediction rate to the PTS1 component of the PSORT2 program. The sensitivity of our predictor in recognising documented PTS1 signal containing proteins is close to 90% for reliable prediction. The predictor distinguishes even SKL-appended non-peroxisomally targeted proteins such as a mouse dihydrofolate reductase-SKL construct. The corresponding rate of false positives is not worse than 0.8%; thus, the tool can be applied for large-scale unsupervised sequence database annotation. A scan of public protein databases uncovered a number of yet uncharacterised proteins for which the PTS1 signal might be critical for biological function. The predicted presence of a PTS1 signal implies peroxisomal localisation in the absence of N-terminal targeting sequences such as the mitochondrial import signal. (C) 2003 Elsevier Science Ltd. All rights reserved.