Identification, analysis, and prediction of protein ubiquitination sites

Radivojac, P., Vacic, V., Haynes, C., Cocklin, R. R., Mohan, A., Heyen, J. W., Goebl, M. G., Iakoucheva, L. M. (February 2010) Identification, analysis, and prediction of protein ubiquitination sites. Proteins-Structure Function and Bioinformatics, 78 (2). pp. 365-380. ISSN 0887-3585

URL: https://www.ncbi.nlm.nih.gov/pubmed/19722269
DOI: 10.1002/prot.22555

Abstract

Ubiquitination plays an important role in many cellular processes and is implicated in many diseases. Experimental identification of ubiquitination sites is challenging due to rapid turnover of ubiquitinated proteins and the large size of the ubiquitin modifier. We identified 141 new ubiquitination sites using a combination of liquid chromatography, mass spectrometry, and mutant yeast strains. Investigation of the sequence biases and structural preferences around known ubiquitination sites indicated that their properties were similar to those of intrinsically disordered protein regions. Using a combined set of new and previously known ubiquitination sites, we developed a random forest predictor of ubiquitination sites, UbPred. The class-balanced accuracy of UbPred reached 72%, with the area under the ROC curve at 80%. The application of UbPred showed that high confidence Rsp5 ubiquitin ligase substrates and protein with very short half-lives were significantly enriched in the number of predicted ubiquitination sites. Proteome-wide prediction of ubiquitination sites in Saccharomyces cerevisiae indicated that highly ubiquitinated substrates were prevalent among transcription/enzyme regulators and proteins involved in cell cycle control. In the human proteome, cytoskeletal, cell cycle, regulatory, and cancer-associated proteins display higher extent of ubiquitination than proteins from other functional categories. We show that gain and loss of predicted ubiquitination sites may likely represent a molecular mechanism behind a number of disease-associated mutations. UbPred is available at http:// www.ubpred.org. Proteins 2010; 78:365-380. (C) 2009 Wiley-Liss, Inc.

Item Type: Paper
Uncontrolled Keywords: UbPred protein ubiquitination sites prediction post-translational modification intrinsically disordered protein unstructured disordered INTRINSICALLY DISORDERED PROTEINS PROTEASOME-MEDIATED DEGRADATION MULTIPLE PHOSPHORYLATION SITES KAPPA-B-ALPHA UNSTRUCTURED PROTEINS HUMAN-DISEASES STRUCTURAL DISORDER CRYSTAL-STRUCTURE DATABASE SEARCH LIGASE COMPLEX
Subjects: bioinformatics > genomics and proteomics > databases > database construction
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein ubiquitination
CSHL Authors:
Communities: CSHL labs > Sebat lab
Depositing User: CSHL Librarian
Date: 1 February 2010
Date Deposited: 04 Oct 2011 15:11
Last Modified: 13 Mar 2018 13:43
PMCID: PMC3006176
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15511

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