title: GPS-ARM: computational analysis of the APC/C recognition motif by predicting D-boxes and KEN-boxes.
abstract: Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and faithfully orchestrates the proper cell cycle events by targeting proteins for proteasomal degradation. Experimental identification of APC/C substrates is largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box and KEN-box. Although a number of either stringent or loosely defined motifs proposed, these motif patterns are only of limited use due to their insufficient powers of prediction. We report the development of a novel GPS-ARM software package which is useful for the prediction of D-boxes and KEN-boxes in proteins. Using experimentally identified D-boxes and KEN-boxes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted. By extensive evaluation and comparison, the GPS-ARM performance was found to be much better than the one using simple motifs. With this powerful tool, we predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes in 1,403 proteins from H. sapiens, while further statistical analysis suggested that both the D-box and KEN-box proteins are involved in a broad spectrum of biological processes beyond the cell cycle. In addition, with the co-localization information, we predicted hundreds of mitosis-specific APC/C substrates with high confidence. As the first computational tool for the prediction of APC/C-mediated degradation, GPS-ARM is a useful tool for information to be used in further experimental investigations. The GPS-ARM is freely accessible for academic researchers at: http://arm.biocuckoo.org.
authors.affiliation: Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zexian
authors.initials: Z
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Ren
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012984:Software; D013379:Substrate Specificity; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D011506:Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome