In this paper we assembled a comprehensive network of the ubiquitin system (Ub-system), namely ubiquitin-like proteins, their conjugation and deconjugation apparatus, binding partners and the proteasomal system. To achieve the best possible network, we integrated numerous ubiquitination/sumoylation datasets with public protein/genetic interaction databases. To aid in the data analysis, we devised two novel representations, the rank plot to understand the functional diversification of different components and the clique-specific point-wise mutual-information network to identify significant interactions in the Ub-system. Using these representations, we found supporting evidence for the functional diversification of SUMO-dependent Ub-ligases. We also identify novel components of SCF complexes, receptors in the ERAD system and a key role for Sus1 in coordinating multiple Ub-related processes in chromatin dynamics. We also identified several modified transcription factors, suggesting an extensive regulatory impact of the Ub system in the cellular networks. Furthermore, the dynamics of the Ub-network suggests that Ub and SUMO modifications might function cooperatively with transcription control in regulating cell-cycle-stage-specific complexes and in reinforcing periodicities in gene expression. Combined with evolutionary information, the structure of this network helps in understanding the lineage-specific expansion of SCF complexes with a potential role in pathogen response and the origin of the ERAD and ESCRT systems.
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