Abstract

The nucleus is the largest and the highly organized organelle of eukaryotic cells. Within nucleus exist a number of pseudo-compartments, which are not separated by any membrane, yet each of them contains only a specific set of proteins. Understanding protein sub-nuclear localization can hence be an important step towards understanding biological functions of the nucleus. Here we have described a method, SubNucPred developed by us for predicting the sub-nuclear localization of proteins. This method predicts protein localization for 10 different sub-nuclear locations sequentially by combining presence or absence of unique Pfam domain and amino acid composition based SVM model. The prediction accuracy during leave-one-out cross-validation for centromeric proteins was 85.05%, for chromosomal proteins 76.85%, for nuclear speckle proteins 81.27%, for nucleolar proteins 81.79%, for nuclear envelope proteins 79.37%, for nuclear matrix proteins 77.78%, for nucleoplasm proteins 76.98%, for nuclear pore complex proteins 88.89%, for PML body proteins 75.40% and for telomeric proteins it was 83.33%. Comparison with other reported methods showed that SubNucPred performs better than existing methods. A web-server for predicting protein sub-nuclear localization named SubNucPred has been established at http://14.139.227.92/mkumar/subnucpred/. Standalone version of SubNucPred can also be downloaded from the web-server.

Highlights

  • Nuclear proteins are produced in cytoplasm from where they are transported to the nucleus

  • Knowledge of proteins sub-nuclear localization is essential for understanding the cellular processes and genomic regulation and to understand the clinico-pathological manifestations caused due to mis-localized nuclear proteins

  • We developed a combined method, SubNucPred, for predicting the sub-nuclear location of nuclear proteins with high accuracy by combining Pfam domain information and Support Vector Machine (SVM) score

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Summary

Introduction

Nuclear proteins are produced in cytoplasm from where they are transported to the nucleus. At present several experimental methods like co-expression of fluorescent proteins [1], electron and fluorescence microscopy [2,3], immuno-fluorescence labeling [4,5], photo-activated localization microscopy [6], liquid-chromatography-tandem mass spectrometry [7,8] etc are available to study protein localization. Alterations in gene expression of proteins located in different sub-nuclear locations may cause cancer and other genetic diseases [9,10]. The prediction of protein localization at the sub-nuclear level is difficult compared to the generalized subcellular level due to (i) absence of physical barrier or membrane within the cell nucleus [11] and (ii) dynamic nature of protein complexes within the nucleus [12]

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