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Bioinformatics Advance Access published online on January 9, 2008
Bioinformatics, doi:10.1093/bioinformatics/btm624
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© 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.

Discovery of candidate KEN box motifs using Cell Cycle keyword enrichment combined with native disorder prediction and motif conservation

Sushama Michael 1, Gilles Travé 1,2, Chenna Ramu 3, Claudia Chica 1 and Toby J. Gibson 1,*

1Structural and Computational Biology Unit, EMBL, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.
2ESBS, 1, Bld Sébastien Brandt, BP10413, 67412-ILLKIRCH-FRANCE.
3Max-Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.

*To whom correspondence should be addressed. Dr. Toby J. Gibson, E-mail: Toby.gibson{at}embl.de


  Abstract

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.

Supplementary Information: Tables of KEN box candidates and keyword/conservation significance assessments are available as supplementary data at Bioinformatics online.

Associate Editor: Prof. Alfonso Valencia

Received on August 3, 2007; revised on December 14, 2007; accepted on December 16, 2007

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