title: Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction.
abstract: The binding affinity between a nuclear localization signal (NLS) and its import receptor is closely related to corresponding nuclear import activity. PTM-based modulation of the NLS binding affinity to the import receptor is one of the most understood mechanisms to regulate nuclear import of proteins. However, identification of such regulation mechanisms is challenging due to the difficulty of assessing the impact of PTM on corresponding nuclear import activities. In this study we proposed NIpredict, an effective algorithm to predict nuclear import activity given its NLS, in which molecular interaction energy components (MIECs) were used to characterize the NLS-import receptor interaction, and the support vector regression machine (SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity. Our experiments showed that nuclear import activity change due to NLS change could be accurately predicted by the NIpredict algorithm. Based on NIpredict, we developed a systematic framework to identify potential PTM-based nuclear import regulations for human and yeast nuclear proteins. Application of this approach has identified the potential nuclear import regulation mechanisms by phosphorylation of two nuclear proteins including SF1 and ORC6.
authors.affiliation: Department of Computer Science and Engineering, University of South Carolina, Columbia, South Carolina, 29208.
authors.forename: Jhih-Rong
authors.initials: JR
authors.lastname: Lin
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000465:Algorithms; D001185:Artificial Intelligence; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D006801:Humans; D020407:Internet; D007700:Kinetics; D008954:Models, Biological; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism*; D051738:Origin Recognition Complex / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D012986:Software Validation; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D028901:alpha Karyopherins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; C497221:ORC6 protein, S cerevisiae; D051738:Origin Recognition Complex; D020033:Protein Isoforms; D000072260:RNA Splicing Factors; C107467:SF1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D028901:alpha Karyopherins; D012694:Serine
keywords: nuclear import regulation; nuclear localization signals; post-translational modification; protein sorting regulation; protein targeting