Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation

Bioinformatics
Sushama MichaelToby J Gibson

Abstract

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. 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.

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Citations

Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael J EmanueleStephen J Elledge
Nov 19, 2009·Nucleic Acids Research·Cathryn M GouldToby J Gibson
Aug 20, 2009·The Journal of Clinical Investigation·Zheng FuDonald J Tindall
Apr 28, 2010·PLoS Genetics·Kazunari KaizuHiroaki Kitano
Nov 12, 2013·Nucleic Acids Research·Holger DinkelToby J Gibson
Feb 14, 2012·Seminars in Cell & Developmental Biology·Mingwei Min, Catherine Lindon
Jul 18, 2008·Translational Oncology·Lisa M Privette, Elizabeth M Petty
Aug 12, 2014·Bioarchitecture·Ilias StavropoulosDenis C Shields
Sep 1, 2011·Molecular BioSystems·Richard J EdwardsDenis C Shields
May 27, 2014·Molecular & Cellular Proteomics : MCP·Mingwei MinCatherine Lindon
Dec 15, 2017·PLoS Computational Biology·Gábor ErdősZsuzsanna Dosztányi

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