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Bionformatical Comparative Study of Human Ubiquitinome

2012; Association of Biomolecular Resource Facilities; Volume: 23; Linguagem: Inglês

1943-4731

Martin Damsbo, Christian Ravnsborg, Alexandre V. Podtelejnikov, G. Gendeh,

Advanced Proteomics Techniques and Applications

Protein ubiquitination is highly dynamic, reversible and versatile modification that plays a significant role in the myriad of biological functions. For many years it has been known to mediate targeting of proteins for degradation by proteasomes, but recent studies showed that ubiquitination also plays an important role in targeting of proteins for ligand-dependent internalization and other nonproteolytic functions involved in as cell growth, apoptosis, DNA damage repair, immune response and others. In current study we focused on the comparative analysis of large scale shotgun ubiquitin-modified proteome analysis using ProteinCenter. Based on a relational database that integrates the contents of a large number of public protein sequence databases, ProteinCenter enables scientists to perform complex comparison studies derived from experimental data, available databases and literature. We used the following data derived from recently published papers: Kim W et.al, Mol Cell. 2011 (~19000 ubq sites), Wagner SA. et. al, Mol Cell Proteomics. 2011 (11054 ubq sites) and Danielsen JM et.al, Mol Cell Proteomics. (753 unique lysine ubiquitination sites). As expected, bioinformatical express analysis of these datasets showed over representation of RNA binding and ligase activity, in particular ubiquitin-protein ligase activity. Over represented KEGG pathways analysis included ribosome, spliceosome pathways and ubiquitin mediated proteolysis as well as some of the signalling pathways. That supports that protein ubiquitination is not only a part of protein degradation but can be involved in the signalling cascade. Surprisingly comparison of the first two dataset gave less than 30% overlap on the protein level and around 10% on the peptide level. Partially it can be explained by differences in purification procedures. Another interesting observation was that a significant number of proteins ubiquitination sites are localised in close proximity. A growing number of experimental evidence on protein ubiquitination determines a general need for software for data collecting, systematization and bioinformatic analysis.