Biopolym. Cell. 2017; 33(2):147-154.
Bioinformatics
Comparative analysis of nuclear localization signal (NLS) prediction methods
1Lisitsyna O. M., 2Seplyarskiy V. B., 1, 3Sheval E. V.
  1. A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University
    Leninskie gory, house 1, building 40, Moscow, Russian Federation, 119992
  2. A. A. Kharkevich Institute for Information Transmission Problems,
    19/1, Bolshoy Karetny per. Moscow, Russian Federation, 127051the Russian Academy of Sciences (Kharkevich Institute), Bolshoi Karetny pereulok 19, 127994 Moscow, Russia.
  3. LIA 1066 French-Russian Joint Cancer Research Laboratory
    Villejuif, France–Moscow, Russian Federation

Abstract

Aim. Comparative analysis of six state-of-the-art nuclear localization signal (NLS) prediction methods (PSORT II, NucPred, cNLSMapper, NLStradamus, NucImport and seqNLS). Methods. Each program was tested for correct predictions using a dataset of 155 experimentally determined NLSs and for false-positives using a dataset of 155 transmembrane proteins, which putatively lack NLS. Results. The most suitable NLS predictors wer fond to be NucPred, NLStradamus and seqNLS; these programs provide the maximum rate of correct to wrong predictions among the tested programs. However, the best results obtained by these programs were only ~ 45 % of the correct predictions. Conclusion. The identification of novel NLSs by predictors still requires experimental verification.
Keywords: nuclear localization signal, prediction

References

[1] Dickmanns A, Kehlenbach RH, Fahrenkrog B. Nuclear pore complexes and nucleocytoplasmic transport: from structure to function to disease. Int Rev Cell Mol Biol. 2015; 320; 171–233.
[2] Sheval EV, Musinova YR. Structural plasticity of the nuclear envelope and the endoplasmic reticulum. Biopolym Cell. 2014; 30(5): 335–42.
[3] Keminer O, Peters R. Permeability of single nuclear pores. Biophys J. 1999; 77(1): 217–28.
[4] Feldherr CM, Akin D. The location of the transport gate in the nuclear pore complex. J Cell Sci. 1997;110 (Pt 24): 3065–70.
[5] Pemberton LF, Paschal BM. Mechanisms of receptor-mediated nuclear import and nuclear export. Traffic. 2005; 6(3): 187–98.
[6] Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH. Classical nuclear localization signals: defini-tion, function, and interaction with importin alpha. J Biol Chem. 2007; 282(8): 5101–5.
[7] Miyamoto Y, Yamada K, Yoneda Y. Importin α: a key molecule in nuclear transport and non-transport functions. J Biochem. 2016; 160(2):69–75.
[8] Lee BJ, Cansizoglu AE, Süel KE, Louis TH, Zhang Z, Chook YM. Rules for nuclear localization sequence recogni-tion by karyopherin beta 2. Cell. 2006; 126(3): 543–58.
[9] Siomi H, Dreyfuss G. A nuclear localization domain in the hnRNP A1 protein. J Cell Biol. 1995; 129(3): 551–60.
[10] Hall MN, Hereford L, Herskowitz I. Targeting of E coli beta-galactosidase to the nucleus in yeast. Cell. 1984; 36(4): 1057–65.
[11] Fischer U, Sumpter V, Sekine M, Satoh T, Luhrmann R. Nucleo-cytoplasmic transport of U snRNPs: definition of a nuclear location signal in the Sm core domain that binds a transport receptor independently of the m3G cap. EMBO J. 1993; 12(2): 573–83.
[12] García-Martín A, Ardura JA, Maycas M, Lozano D, López-Herradón A, Portal-Nú-ez S, García-Oca-a A, Esbrit P. Functional roles of the nuclear localization signal of parathyroid hormone-related protein (PTHrP) in os-teoblastic cells. Mol Endocrinol. 2014; 28: 925–34.
[13] Lee SJ, Sekimoto T, Yamashita E, Nagoshi E, Naka-ga-wa A, Imamoto N, Yoshimura M, Sakai H, Chong KT, Tsukihara T, Yoneda Y. The structure of importin beta bound to SREBP 2: nuclear import of a transcription fac-tor. Science. 2003; 302(5650): 1571–5.
[14] Marfori M, Mynott A, Ellis JJ, Mehdi AM, Saunders NFW, Curmi PM, Forwood JK, Bodén M, Kobe B. Molecular basis for specificity of nuclear import and prediction of nuclear localization. BBA – Mol Cell Res. 2011; 1813(9): 1562–77.
[15] Wühr M, Güttler T, Peshkin L, McAlister GC, Sonnett M, Ishihara K, Groen AC, Presler M, Erickson BK, Mitchi-son TJ, Kirschner MW, Gygi SP. The nuclear proteome of a vertebrate. Curr Biol. 2015; 25(20): 2663–71.
[16] Nagarajan UM, Long AB, Harreman M, Corbett A, Boss JM. A hierarchy of nuclear localization signals governs the import of the regulatory factor X complex subunits and MHC class II expression. J Immunol. 2004; 173(24): 410–419.
[17] Chelsky D, Ralph R, Jonak G. Sequence requirements for synthetic peptide-mediated translocation to the nucleus. Mol Cell Biol. 1989; 9(6): 2487–92.
[18] Hodel MR, Corbett AH, Hodel AE. Dissection of a nuclear localization signal. J Biol Chem. 2001; 276(2): 1317–25.
[19] Fontes MRM, Teh T, Jan D, Brinkworth RI, Kobe B. Structural basis for the specificity of bipartite nuclear local-ization sequence binding by importin-alpha. J Biol Chem. 2003; 278(30): 27981–7.
[20] Kosugi S, Hasebe M, Entani T, Takayama S, Tomita M, Yanagawa H. Design of peptide inhibitors for the im-portin α/β nuclear import pathway by activity-based profiling. Chem Biol. 2008; 15(9): 940–9.
[21] Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocyto-plasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A. 2009; 106(25): 10171–6.
[22] Robbins J, Dilworth SM, Laskey RA, Dingwall C. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: Identification of a class of bipartite nuclear targeting sequence. Cell. 1991; 64(3): 615–23.
[23] Matthews BW. Comparison of the predicted and observed secondary structure of T4 phage lysozyme. BBA - Pro-tein Struct. 1975; 405(2): 442–51.
[24] Nakai K, Kanehisa M. A knowledge base for predicting protein localization sites in eukaryotic cells. Genomics. 1992; 14(4): 897–911.
[25] Brameier M, Krings A, MacCallum RM. NucPred – predicting nuclear localization of proteins. Bioinformatics 2007; 23(9): 1159–60.
[26] Nguyen Ba AN, Pogoutse A, Provart N, Moses AM. NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction. BMC Bioinformatics. 2009; 10(1): 202.
[27] Mehdi AM, Sehgal MSB, Kobe B, Bailey TL, Bodén M. A probabilistic model of nuclear import of proteins. Bioin-formatics. 2011; 27(9): 1239–46.
[28] Lin J, Hu J. SeqNLS: nuclear localization signal prediction based on frequent pattern mining and linear motif scoring. PLoS One. 2013; 8(10): e76864.