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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 ∼800 proteins in human, fly, worm and yeast.
EMBO Reports – Wiley
Published: Nov 1, 2000
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