E3Net is a web based system that provides a comprehensive collection of available E3 substrate specificities and a systematic framework for the analysis of E3 mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms, and 1671 E3 substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection, and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3 specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3 substrate networks and their correlated functions with graphical illustrations and summarized descriptions