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Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network
Open accessAbstract
In eukaryotic cells the stability and function of many proteins are regulated by the addition of ubiquitin or ubiquitin-like peptides. This process is dependent upon the sequential action of an E1-activating enzyme, an E2-conjugating enzyme, and an E3 ligase. Different combinations of these proteins confer substrate specificity and the form of protein modification. However, combinatorial preferences within ubiquitination networks remain unclear. In this study, yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions. These data include 535 experimentally defined novel E2/E3-RING interactions and >1300 E2/E3-RING pairs with more favorable predicted free-energy values than the canonical UBE2L3-CBL complex. The significance of Y2H predictions was assessed by both mutagenesis and functional assays. Significantly, 74/80 (>92%) of Y2H predicted complexes were disrupted by point mutations that inhibit verified E2/E3-RING interactions, and a approximately 93% correlation was observed between Y2H data and the functional activity of E2/E3-RING complexes in vitro. Analysis of the high-density human E2/E3-RING network reveals complex combinatorial interactions and a strong potential for functional redundancy, especially within E2 families that have undergone evolutionary expansion. Finally, a one-step extended human E2/E3-RING network, containing 2644 proteins and 5087 edges, was assembled to provide a resource for future functional investigations.
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“The ability of E3 ligases to interact with multiple E2 partners is supported by recent global E2-E3 interaction screens (26,27).”
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“However, some of these E2 s failed to interact with Mdm2 in another high throughput approach [26].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [26]
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Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Towards a proteome-scale map of the human protein–protein interaction network
Rual, J.-F. M., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G. F., Gibbons, F. D., Dreze, M., Ayivi-Guedehoussou, N., et al. (2005) · Nature · doi:10.1038/nature04209 · Cited by 2,904
Self-citationThe FoldX web server: an online force field
Schymkowitz, J., Borg, J., Stricher, F., Nys, R., Rousseau, F., & Serrano, L. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki387 · Cited by 2,759 · cited 1×
“Homology modeling was then achieved by replacing side-chain residues in accordance with structure-based alignments (Supplemental Files 7 and 8) using the BuildModel command of FoldX (Guerois et al. 2002; Schymkowitz et al. 2005a,b) vs 2.7.”
MethodInfluentialSelf-citationA Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome
Stelzl, U., Worm, U., Lalowski, M. M., Haenig, C., Brembeck, F. H., Goehler, H., Strödicke, M., Zenkner, M., Schoenherr, A., Koeppen, S., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.029 · Cited by 2,433
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Mammalian Gene Collection (MGC) Program Team* (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242603899 · Cited by 1,756
Guerois, R., Nielsen, J. E., & Serrano, L. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00442-4 · Cited by 1,728
Self-citationA proteomics approach to understanding protein ubiquitination
Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D. J., & Gygi, S. P. (2003) · Nature Biotechnology · doi:10.1038/nbt849 · Cited by 1,601
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase
Joazeiro, C. A. P., Wing, S. S., Huang, H.-K., Leverson, J. D., Hunter, T. R., & Liu, Y. (1999) · Science · doi:10.1126/science.286.5438.309 · Cited by 1,036
Ubiquitin and ubiquitin-like proteins as multifunctional signals
Welchman, R., Gordon, C., & Mayer, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1700 · Cited by 849
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Uhler, J. P., Spåhr, H., Farge, G., Clavel, S., Larsson, N., Falkenberg, M., Samuelsson, T., & Gustafsson, C. M. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.10.137 · Cited by 19
Poh, J., Ponsford, A. H., Boyd, J., Woodsmith, J., Stelzl, U., Wanker, E. E., Harper, N., MacEwan, D. J., & Sanderson, C. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101686 · Cited by 17
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Zhang, N., & Bilsland, E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-173-4_28 · Cited by 17
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Gundelfinger, E. D., Karpova, A., Pielot, R., Garner, C. C., & Kreutz, M. R. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.829354 · Cited by 19
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Ma, N., Li, Z., Yan, J., Liu, X., He, L., Xie, R., & Lu, X. (2023) · Oncology Reports · doi:10.3892/or.2023.8506 · Cited by 16
To Ubiquitinate or Not to Ubiquitinate: TRIM17 in Cell Life and Death
Basu-Shrivastava, M., Kozoriz, A., Desagher, S., & Lassot, I. (2021) · Cells · doi:10.3390/cells10051235 · Cited by 15
Waddell, D. S., Duffin, P. J., Haddock, A. N., Triplett, V. E., Saredy, J., Kakareka, K. M., & Eldredge, J. T. (2015) · Gene · doi:10.1016/j.gene.2015.10.046 · Cited by 13
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Nourreddine, S., Doctor, Y., Dailamy, A., Forget, A., Lee, Y.-H., Chinn, R., Khaliq, H., Polacco, B. J., Muralidharan, M., Pan, E., et al. (2026) · Nature Biotechnology · doi:10.1038/s41587-026-03199-w · Cited by 14
Ray, P., Nancarrow, D. J., Ferrer-Torres, D., Wang, Z., Martinho, M. S., Hinton, T., Wu, J. H., Wu, A., Turgeon, D. K., Hammer, M. A., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.08.003 · Cited by 12
Polge, C., Aniort, J., Armani, A., Claustre, A., Coudy‐Gandilhon, C., Tournebize, C., Deval, C., Combaret, L., Béchet, D., Sandri, M., et al. (2018) · Cells · doi:10.3390/cells7110214 · Cited by 12
Guo, Y., An, L., Ng, H.-M., Sy, S. M.-H., & Huen, M. S. Y. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.758854 · Cited by 13
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Ying, M., Huang, X., Zhao, H., Wu, Y., Wan, F., Huang, C., & Jie, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023863 · Cited by 11
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Murata, Y., Bundo, M., Sunaga, F., Kasai, K., & Iwamoto, K. (2018) · Pharmacopsychiatry · doi:10.1055/s-0044-101467 · Cited by 11
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Shoji, S., Hanada, K., Ohsawa, N., & Shirouzu, M. (2017) · Biochemical Journal · doi:10.1042/bcj20161104 · Cited by 9
Concise machinery for monitoring ubiquitination activities using novel artificial RING fingers
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Larabee, C. M., Georgescu, C., Wren, J. D., & Plafker, S. M. (2015) · BMC Neuroscience · doi:10.1186/s12868-015-0194-y · Cited by 7
Zhong, F., Chen, H., Jin, Y., Guo, S., Wang, W., & Chen, N. (2012) · Inflammation · doi:10.1007/s10753-012-9522-x · Cited by 6
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Regulation of LIM-domain-binding 1 protein expression by ubiquitination of Lys134
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Wilson, B. A. P., Voeller, D. M., Smith, E. A., Wamiru, A., Goncharova, E. I., Liu, G., Lipkowitz, S., & O’Keefe, B. R. (2021) · SLAS DISCOVERY · doi:10.1177/24725552211000675 · Cited by 6
Ponce-Toledo, R. I., Moreira, D., López-García, P., & Deschamps, P. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf167 · Cited by 5
NMR characterization of foldedness for the production of E3 RING domains
Huang, A., de Jong, R. N., Folkers, G. E., & Boelens, R. (2010) · Journal of Structural Biology · doi:10.1016/j.jsb.2010.07.014 · Cited by 6
Zhang, Y., Wang, Y., Yang, J., Zhang, J., Sun, L., Hirankarn, N., Pan, H., Lau, C. S., Chan, T. M., Lee, T. L., et al. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0577-6 · Cited by 5
An optical and non‐invasive method to detect the accumulation of ubiquitin chains
Imai, J., Koganezawa, Y., Tuzuki, H., Ishikawa, I., & Sakai, T. (2019) · Cell Biology International · doi:10.1002/cbin.11186 · Cited by 4
Błaszczak, E., Prigent, C., & Rabut, G. E. E. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3756-1_13 · Cited by 4
Harris, M. J., Chen, H., Cai, T., Yi, Y., Deng, Q., Yao, Y., Lan, T., Guo, Y., Xu, X., Wen, X., et al. (2022) · ACS Synthetic Biology · doi:10.1021/acssynbio.1c00397 · Cited by 4
Paiva, R., Saliba, A. M., Fulco, T. D. O., Sales, J. D. S., de Carvalho, D. S., Sampaio, E. P., Lopes, U. G., Sarno, E. N., & Nobre, F. F. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-292 · Cited by 2
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Hao, M., Dou, Z., Xu, L. K., Shao, Z., Sun, H., & Li, Z. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/3793946 · Cited by 2
Trezza, R. A., van den Burg, J., van den Oever, N., & Distel, B. (2018) · Microbial Cell · doi:10.15698/mic2018.03.620 · Cited by 2
LV, Y., & Xing, F. (2022) · TURKISH JOURNAL OF BIOLOGY · doi:10.55730/1300-0152.2585 · Cited by 1
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Abou Zeinab, R. M. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3610vx4f · Cited by 1
Characterization of the cellular network of ubiquitin conjugating and ligating enzymes
Błaszczak, E. (2015) · HAL · doi:10.70675/65f55822zf1c4z4a86zb239z1c48022e6cc7 · Cited by 1
Identification and Functional Studies of Arabidopsis thaliana Ubc13-interacting E3 Ubiquitin Ligases
Qian, S. (2012) · University Library - University of Saskatchewan (University of Saskatchewan)
Anandapadamanaban, M. (2015) · Linköping University Electronic Press eBooks · doi:10.3384/diss.diva-122468
Worseck, J. M. (2012) · edoc Publication server (Humboldt University of Berlin) · doi:10.18452/16533
Differential expressed genes of banana leaves induced by Fusarium wilt disease
Tie-cheng, P. E. N. G., Chen, Y. Y., Jing-yao, L. U. O., Zhao, H., Lei, M. U., Xie, J., Wei, S., Xia, Y., & Tang, H. P. (2015) · Molecular Plant Breeding · doi:10.5376/mpb
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Sorrentino, V. (2014) · UvA-DARE (University of Amsterdam)
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Werner, A. A. (2011) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3303
The Role Of Mitochondrial Omi/htra2 Protease In Protein Quality Control And Mitophagy
Ambivero, C. T. (2013) · Journal of International Crisis and Risk Communication Research
Targeting the major regulator of mitosis.
Hoffman, J. (2017) · doi:10.18297/etd/2879
Loss of UBE2O Mitigates Beta Thalassemia Through Broad Proteomic Changes
Nguyen, A. T. (2018) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Miyamoto, K., & Saito, K. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8799-3_6
Tian, J., Wu, Z., Zhang, Y., He, Y., & Liu, S. (2020) · Research Square · doi:10.21203/rs.3.rs-86136/v1
The ubiquitination enzymes of Leishmania mexicana
Burge, R. J. (2020) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Metabolic reprogramming and redox perturbations
Aboushousha, R. (2021) · Research Publications (Maastricht University) · doi:10.26481/dis.20211208ra
Tian, J., Wu, Z., He, Y., & Liu, S. (2020) · doi:10.21203/rs.3.rs-34924/v2
Vázquez, J. A., Nyenhuis, D. A., Strub, M., & Tjandra, N. (2025) · Biomolecular NMR Assignments · doi:10.1007/s12104-025-10240-7
Pourcelot, M. (2016) · theses.fr (ABES) · doi:10.70675/fe9bf786z6d4ez45d5zb047z4cff0d131b1c
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Ristic, M. (2015) · theses.fr (ABES) · doi:10.70675/2176c900z3348z4cc3z8402z8c35404016b0
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Zemirli, N. (2014) · theses.fr (ABES) · doi:10.70675/098ff617z3ed6z43caz9f51z004f55dce561
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Snacel-Fazy, E. (2023) · theses.fr (ABES) · doi:10.70675/7e5e377fzaaa9z4f1dzbde6z9586007f6c3d
Shah, R., Bulusu, S., Shah, H., Doshi, A., & Pandya, P. (2026) · Gene Reports · doi:10.1016/j.genrep.2026.102547
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Ringelstetter, L., Mersdorf-Weber, E., Schorpp, K., & Hadian, K. (2026) · RSC Chemical Biology · doi:10.1039/d5cb00209e
Metadata
- Authors
- Markson, G., Kiel, C., Hyde, R., Brown, S., Charalabous, P., Bremm, A., Semple, J., Woodsmith, J., Duley, S., Salehi-Ashtiani, K., Vidal, M., Komander, D., Serrano, L., Lehner, P., & Sanderson, C. M.
- Affiliations
- University of Cambridge (GB)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of Liverpool (GB)
- MRC Laboratory of Molecular Biology (GB)
- Harvard University (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-06-23
- Volume
- 19
- Issue
- 10
- Pages
- 1905-1911
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2765280
- OpenAlex
- W2135700703
- Cited by
- 157
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 10 · 2019: 3 · 2018: 11 · 2017: 7 · 2016: 12 · 2015: 19 · 2014: 6 · 2013: 17 · 2012: 18
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (084957)
- Fonds De La Recherche Scientifique - FNRS
- Fédération Wallonie-Bruxelles
- Medical Research Council
- National Human Genome Research Institute (R01HG001715)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- E2 ubiquitin-conjugating enzyme, E3 ubiquitin ligase, RING domain, protein-protein interaction network, ubiquitination, yeast two-hybrid screen, homology modeling, free energy prediction, functional redundancy, human interactome
- MeSH terms
- Amino Acid Sequence, False Positive Reactions, Humans, Protein Binding, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, K562 Cells, Sequence Analysis, Protein, Two-Hybrid System Techniques, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Metabolic Networks and Pathways, Protein Interaction Domains and Motifs, Ubiquitination
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