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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents

ID: 404430.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation
Authors:Sushama, Michael; Gilles, Travé; Chenna, Ramu; Chica, Claudia; Gibson, Toby J.
Date of Publication (YYYY-MM-DD):2008-01-09
Title of Journal:Bioinformatics
Issue / Number:4
Start Page:453
End Page:457
Full name of Issue-Editor(s):Associate Editor: Alfonso Valencia
Copyright:© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Motivation: KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C complex. While annotating the Eukaryotic Linear Motif resource (ELM, http://elm.eu.org/), we found that KEN motifs were significantly enriched in human protein entries with cell cycle keywords in the UniProt/Swiss-Prot database—implying that KEN-boxes might be more common than reported.

Results: Matches to short linear motifs in protein database searches are not, per se, significant. KEN-box enrichment with cell cycle Gene Ontology terms suggests that collectively these motifs are functional but does not prove that any given instance is so. Candidates were surveyed for native disorder prediction using GlobPlot and IUPred and for motif conservation in homologues. Among >25 strong new candidates, the most notable are human HIPK2, CHFR, CDC27, Dab2, Upf2, kinesin Eg5, DNA Topoisomerase 1 and yeast Cdc5 and Swi5. A similar number of weaker candidates were present. These proteins have yet to be tested for APC/C targeted destruction, providing potential new avenues of research.
Comment of the Author/Creator:Contact: toby.gibson@embl.de

Supplementary information: Tables of KEN-box candidates and keyword/conservation significance assessments are available as supplementary data at Bioinformatics online.
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Structural and Computational Biology Unit, EMBL, Meyerhofstrasse 1, D-69117, Heidelberg, Germany,
2.ESBS, 1, Bld Sébastien Brandt, BP10413, 67412-ILLKIRCH-FRANCE.
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