UbiNet 2.0: a verified, classified, annotated and updated database of E3 ubiquitin ligase-substrate interactions.

Ubiquitination is an important post-translational modification, which controls protein turnover by labeling malfunctional and redundant proteins for proteasomal degradation, and also serves intriguing non-proteolytic regulatory functions. E3 ubiquitin ligases, whose substrate specificity determines the recognition of target proteins of ubiquitination, play crucial roles in ubiquitin-proteasome system. UbiNet 2.0 is an updated version of the database UbiNet. It contains 3332 experimentally verified E3-substrate interactions (ESIs) in 54 organisms and rich annotations useful for investigating the regulation of ubiquitination and the substrate specificity of E3 ligases. Based on the accumulated ESIs data, the recognition motifs in substrates for each E3 were also identified and a functional enrichment analysis was conducted on the collected substrates. To facilitate the research on ESIs with different categories of E3 ligases, UbiNet 2.0 performed strictly evidence-based classification of the E3 ligases in the database based on their mechanisms of ubiquitin transfer and substrate specificity. The platform also provides users with an interactive tool that can visualize the ubiquitination network of a group of self-defined proteins, displaying ESIs and protein-protein interactions in a graphical manner. The tool can facilitate the exploration of inner regulatory relationships mediated by ubiquitination among proteins of interest. In summary, UbiNet 2.0 is a user-friendly web-based platform that provides comprehensive as well as updated information about experimentally validated ESIs and a visualized tool for the construction of ubiquitination regulatory networks available at http://awi.cuhk.edu.cn/~ubinet/index.php.