Finding nuclear localization signals.
A variety of nuclear localization signals (NLSs) are experimentally known although only one motif was available for database searches through PROSITE. We initially collected a set of 91 experimentally verified NLSs from the literature. Through iterated 'in silico mutagenesis' we then extended the set to 214 potential NLSs. This final set matched in 43% of all known nuclear proteins and in no known non-nuclear protein. We estimated that >17% of all eukaryotic proteins may be imported into the nucleus. Finally, we found an overlap between the NLS and DNA-binding region for 90% of the proteins for which both the NLS and DNA-binding regions were known. Thus, evolution seemed to have used part of the existing DNA-binding mechanism when compartmentalizing DNA-binding proteins into the nucleus. However, only 56 of our 214 NLS motifs overlapped with DNA-binding regions. These 56 NLSs enabled a de novo prediction of partial DNA-binding regions for approximately 800 proteins in human, fly, worm and yeast.
CUBIC, Columbia University, Department of Biochemistry and Molecular Biophysics, New York, NY 10032, USA.
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Cokol
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Nair
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Rost
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry; D016208:Databases, Factual; D016678:Genome; D006801:Humans; D008954:Models, Biological; D016296:Mutagenesis; D019913:Nuclear Localization Signals; D021381:Protein Transport; D012313:RNA / Q000378:metabolism; D012984:Software
D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; D012313:RNA; D004247:DNA