PEDS Advance Access published online on August 16, 2004
Protein Engineering Design and Selection, doi:10.1093/protein/gzh062
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1 Center for Biological Sequence Analysis, Biocentrum-DTU, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark
* To whom correspondence should be addressed. E-mail: brunak{at}cbs.dtu.dk.
We present here a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NES) are extremely important regulators of the subcellular location of proteins. This regulation has impact on transcription and other nuclear processes, which are fundamental to the viability of the cell. Nuclear export signals are studied in relation to cancer, the cell-cycle, cell differentiation and other important aspects of molecular biology. Our conclusion from this analysis is that the most important properties of NES are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden Markov models in the prediction algorithm and verify the method on the most recently discovered nuclear export signals. The NES predictor (NetNES) is made available for general use at http://www.cbs.dtu.dk/.
Accepted July 28, 2004
Article
Analysis and prediction of leucine-rich nuclear export signals
2 Department of Protein Chemistry, Institute of Molecular Biology, University of Copenhagen, 
ster Farimagsgade 2A, DK-1353 Copenhagen K, Denmark
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