UbiNet

Welcome to UbiNet

UbiNet is a knowledge-based system that could provide potential E3 ligases for ubiquitinated proteins by the information of protein-protein interactions and substrate site specificities. In eukaryotes, protein ubiquitination catalyzed by E3 ubiquitin ligases plays crucial roles in regulating a variety of biological processes. With the high-throughput of mass spectrometry-based proteomics, a number of methods have been developed to experimentally determine the ubiquitination sites, leading to an increasing of large-scale ubiquitinome data. However, at the moment, there exists no resource designed to explore the regulatory networks of E3 ligases for ubiquitinated proteins in humans. Therefore, the UbiNet was designed to provide a full investigation of protein ubiquitination networks by integrating all available ubiquitinome datasets, experimentally verified E3 ligases, and protein-protein interactions. Moreover, UbiNet could provide potential E3 ligases for ubiquitinated proteins by the information of protein-protein interactions and substrate site specificities. The UbiNet could help users to identify E3 ligase-mediated ubiquitination networks and their roles in biological processes.

E3 ubiquitin ligase Cbl (Magentas) in complex with E2 (Cyan) and substrate peptide (Green).

Statistics	Number
Ubiquitinated proteins	14,692
- Ubiquitination sites	43,948
E1 (activating enzyme)	2
E2 (conjugating enzyme)	46
E3 (ubiquitin ligase)	499
Protein-protein interaction	430,530
Domain-domain interaction	286,758
E3-associated functional category	2,143
Literatures	44,184

System flow of UbiNet

Protein ubiquitination catalyzed by E3 ubiquitin ligases plays crucial roles in the regulation of various biological processes. With the emergence of high-throughput mass spectrometry-based proteomics, a number of experimental methods have been developed to identification of ubiquitination sites, leading to the generation of large-scale ubiquitinome data. However, there is a lack of tools designed to explore the regulatory networks of E3 ligases for ubiquitinated proteins. Therefore, UbiNet was designed to provide a full investigation of protein ubiquitination networks by integrating all available ubiquitinome datasets, experimentally verified E3 ligases, and protein-protein interactions. The UbiNet database has collected 43948 experimentally verified ubiquitination sites from 14692 ubiquitinated proteins of humans. Additionally, we have manually curated 499 human E3 ligases along with 1240 functional annotations and 28968 protein domains. To delineate the regulatory networks between E3 ligases and ubiquitinated proteins, 430530 protein-protein interactions were integrated to investigate the ubiquitination networks for a group of interested proteins by a well-established network viewer.

Ubiquitin and its seven Lysine residues

The ubiquitin-proteasome pathway

The highlighted on ubiquitin, the ubiquitin-proteasome Pathway, and crucial roles of E3 ligase:

♣	Ubiquitin is a small protein that consists of 76 amino acids with the weight of 8.5 kDa. Ubiquitin maintains its seven Lysine residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys48, and Lys63). The polyubiquitin can be formed through a bond between the C-terminal glycine of one ubiquitin molecule and an ϵ-amine of any one of the seven Lysine residues from another ubiquitin.
♣	Ubiquitin conjugation sites of protein (also known as Ubiquitination or Ubiquitylation), an essential post-translational modification, is a sequential process that involves in three major enzymes including: E1 (activating enzyme), E2 (conjugating enzyme) and E3 (ubiquitin ligase). The ubiquitin-Proteasome Pathway is a complex and multi-step process, relating to a highly organized cascade of enzymatic reactions that select, mark, and degrades proteins. Firstly, the ubiquitination pathway is activated by attaching C-terminal residue of ubiquitin to a Cys sulphydryl residue in E1 enzyme. Secondly, ubiquitin attached to an E1 is transferred to an E2, which can be conjugated with various E3s. Ubiquitin-protein ligase E3 recognizes a specific protein substrate and catalyzes the transfer of activated ubiquitin to it. Finally, the substrate is sent to 26S proteasome for degradation
♣	The ubiquitin ligase (E3 ligases) play a key role in regulating specific functions by recognizing or regulating a specific group of substrate proteins for ubiquitination. The presence of various different E3s and their substrate specificity indicate that the degradation process, which is one of the important regulatory mechanisms in cellular processes, is specifically controlled by E3s

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Welcome to UbiNet