PEDS Advance Access originally published online on August 16, 2004
Protein Engineering Design and Selection 2004 17(6):527-536; doi:10.1093/protein/gzh062
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Analysis and prediction of leucine-rich nuclear export signals
1Center for Biological Sequence Analysis, Biocentrum-DTU, Technical University of Denmark, Building 208, DK-2800 Lyngby and 3Department of Protein Chemistry, Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen K, Denmark
4 To whom correspondence should be addressed. E-mail: brunak{at}cbs.dtu.dk
We present 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 (NESs) are extremely important regulators of the subcellular location of proteins. This regulation has an impact on transcription and other nuclear processes, which are fundamental to the viability of the cell. NESs 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 NESs 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 NESs. The NES predictor (NetNES) is made available for general use at http://www.cbs.dtu.dk/.
Received June 15, 2004; accepted July 28, 2004.
Edited by P.Balaram
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. M. Romero, M. Irisarri, P. Roth, A. Cauerhff, C. Samakovlis, and P. Wappner Regulation of the Drosophila Hypoxia-Inducible Factor {alpha} Sima by CRM1-Dependent Nuclear Export Mol. Cell. Biol., May 15, 2008; 28(10): 3410 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kulisz and H.-G. Simon An Evolutionarily Conserved Nuclear Export Signal Facilitates Cytoplasmic Localization of the Tbx5 Transcription Factor Mol. Cell. Biol., March 1, 2008; 28(5): 1553 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. DeLotto, Y. DeLotto, R. Steward, and J. Lippincott-Schwartz Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels during Drosophila embryogenesis Development, December 1, 2007; 134(23): 4233 - 4241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schmidt von Braun, A. Sabetti, P. J. Hanic-Joyce, J. Gu, E. Schleiff, and P. B. M. Joyce Dual targeting of the tRNA nucleotidyltransferase in plants: not just the signal J. Exp. Bot., December 1, 2007; 58(15-16): 4083 - 4093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Goulet, G. Gauvin, S. Boisvenue, and J. Cote Alternative Splicing Yields Protein Arginine Methyltransferase 1 Isoforms with Distinct Activity, Substrate Specificity, and Subcellular Localization J. Biol. Chem., November 9, 2007; 282(45): 33009 - 33021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Kim, S.-Y. Kim, and H. Lee Identification and Characterization of Human Cdc7 Nuclear Retention and Export Sequences in the Context of Chromatin Binding J. Biol. Chem., October 12, 2007; 282(41): 30029 - 30038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Goodier, L. Zhang, M. R. Vetter, and H. H. Kazazian Jr. LINE-1 ORF1 Protein Localizes in Stress Granules with Other RNA-Binding Proteins, Including Components of RNA Interference RNA-Induced Silencing Complex Mol. Cell. Biol., September 15, 2007; 27(18): 6469 - 6483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nilsen, K. R. Rosendal, V. Sorensen, J. Wesche, S. Olsnes, and A. Wiedlocha A Nuclear Export Sequence Located on a beta-Strand in Fibroblast Growth Factor-1 J. Biol. Chem., September 7, 2007; 282(36): 26245 - 26256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. West, J. B. Hedges, K.-Y. Lo, and A. W. Johnson Novel Interaction of the 60S Ribosomal Subunit Export Adapter Nmd3 at the Nuclear Pore Complex J. Biol. Chem., May 11, 2007; 282(19): 14028 - 14037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. Pickard, A. B. Hodsman, L. J. Fraher, and P. H. Watson Type 1 Parathyroid Hormone Receptor (PTH1R) Nuclear Trafficking: Regulation of PTH1R Nuclear-Cytoplasmic Shuttling by Importin-{alpha}/{beta} and Chromosomal Region Maintenance 1/Exportin 1 Endocrinology, May 1, 2007; 148(5): 2282 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Beaudoin and S. Labbe Crm1-Mediated Nuclear Export of the Schizosaccharomyces pombe Transcription Factor Cuf1 during a Shift from Low to High Copper Concentrations Eukaryot. Cell, May 1, 2007; 6(5): 764 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Reed, G. Howell, S. M. Harrison, K.-A. Spencer, and J. A. Hiscox Characterization of the Nuclear Export Signal in the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein J. Virol., April 15, 2007; 81(8): 4298 - 4304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Stevens and R. S. Mann A Balance Between Two Nuclear Localization Sequences and a Nuclear Export Sequence Governs Extradenticle Subcellular Localization Genetics, April 1, 2007; 175(4): 1625 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Honda and K. Nakajima Mouse Disabled1 (DAB1) Is a Nucleocytoplasmic Shuttling Protein J. Biol. Chem., December 15, 2006; 281(50): 38951 - 38965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Hao, X. Li, T. Qiao, R. Du, G. Zhang, and D. Fan Subcellular Localization of CIAPIN1 J. Histochem. Cytochem., December 1, 2006; 54(12): 1437 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jiang, M. V. Olson, D. R. Medrano, O.-H. Lee, J. Xu, Y. Piao, M. M. Alonso, C. Gomez-Manzano, M.-C. Hung, W K A. Yung, et al. A novel CRM1-dependent nuclear export signal in adenoviral E1A protein regulated by phosphorylation FASEB J, December 1, 2006; 20(14): 2603 - 2605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Colnaghi, C. M. Connell, R. M. A. Barrett, and S. P. Wheatley Separating the Anti-apoptotic and Mitotic Roles of Survivin J. Biol. Chem., November 3, 2006; 281(44): 33450 - 33456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lischka, C. Rauh, R. Mueller, and T. Stamminger Human Cytomegalovirus UL84 Protein Contains Two Nuclear Export Signals and Shuttles between the Nucleus and the Cytoplasm. J. Virol., October 1, 2006; 80(20): 10274 - 10280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, N. Kakinuma, Y. Zhu, and R. Kiyama Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of {beta}-catenin J. Cell Sci., October 1, 2006; 119(19): 4002 - 4010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Seiser, A. E. Sundberg, B. J. Wollam, P. Zobel-Thropp, K. Baldwin, M. D. Spector, and D. E. Lycan Ltv1 Is Required for Efficient Nuclear Export of the Ribosomal Small Subunit in Saccharomyces cerevisiae Genetics, October 1, 2006; 174(2): 679 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Albor, S. El-Hizawi, E. J. Horn, M. Laederich, P. Frosk, K. Wrogemann, and M. Kulesz-Martin The Interaction of Piasy with Trim32, an E3-Ubiquitin Ligase Mutated in Limb-girdle Muscular Dystrophy Type 2H, Promotes Piasy Degradation and Regulates UVB-induced Keratinocyte Apoptosis through NF{kappa}B J. Biol. Chem., September 1, 2006; 281(35): 25850 - 25866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Y. Tong, J.-J. Guo, A.-L. Huang, H. Liu, C.-D. Hu, S. S. M. Chung, and B. C. B. Ko Regulation of Nucleocytoplasmic Trafficking of Transcription Factor OREBP/TonEBP/NFAT5 J. Biol. Chem., August 18, 2006; 281(33): 23870 - 23879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wernersson, K. Rapacki, H.-H. Staerfeldt, P. W. Sackett, and A. Molgaard FeatureMap3D--a tool to map protein features and sequence conservation onto homologous structures in the PDB. Nucleic Acids Res., July 1, 2006; 34(suppl_2): W84 - W88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Li, P. J. Davidson, N. Y. Lin, R. J. Patterson, J. L. Wang, and E. J. Arnoys Transport of galectin-3 between the nucleus and cytoplasm. II. Identification of the signal for nuclear export Glycobiology, July 1, 2006; 16(7): 612 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Park and K. Luger The structure of nucleosome assembly protein 1 PNAS, January 31, 2006; 103(5): 1248 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakagawa, Y. Hosokawa, M. Yonezumi, K. Izumiyama, R. Suzuki, S. Tsuzuki, M. Asaka, and M. Seto MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10 Blood, December 15, 2005; 106(13): 4210 - 4216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. You, B. K. Dove, L. Enjuanes, M. L. DeDiego, E. Alvarez, G. Howell, P. Heinen, M. Zambon, and J. A. Hiscox Subcellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein J. Gen. Virol., December 1, 2005; 86(12): 3303 - 3310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Naoe, K. Arita, H. Hashimoto, H. Kanazawa, M. Sato, and T. Shimizu Structural Characterization of Calcineurin B Homologous Protein 1 J. Biol. Chem., September 16, 2005; 280(37): 32372 - 32378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Z. Scheifele, E. P. Ryan, and L. J. Parent Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein J. Virol., July 15, 2005; 79(14): 8732 - 8741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. I. Olason Integrating protein annotation resources through the Distributed Annotation System Nucleic Acids Res., July 1, 2005; 33(suppl_2): W468 - W470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Thompson, C. L. Robinson-Benion, and J. T. Holt An Amino-terminal Motif Functions as a Second Nuclear Export Sequence in BRCA1 J. Biol. Chem., June 10, 2005; 280(23): 21854 - 21857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ferrer, J. A. Rodriguez, E. A. Spierings, J. P. de Winter, G. Giaccone, and F. A.E. Kruyt Identification of multiple nuclear export sequences in Fanconi anemia group A protein that contribute to CRM1-dependent nuclear export Hum. Mol. Genet., May 15, 2005; 14(10): 1271 - 1281. [Abstract] [Full Text] [PDF]
|
|