GO:0031371 ubiquitin conjugating enzyme complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031371 (ubiquitin conjugating enzyme complex, synonym E2 complex) is a cellular component defined as any complex that possesses ubiquitin conjugating enzyme activity.
• E2 complexes are the central ubiquitin transfer platforms of the ubiquitin-proteasome system, accepting ubiquitin from E1 and delivering it to E3 ligases or substrates.
• The human genome encodes multiple E2 enzymes, including UBE2C, UBE2N, UBE2O, UBE2S and Ubc11, each with distinct roles in cell cycle, proteostasis, viral maturation and chromatin regulation [1,2,4,5,6,7,8].
• Dysregulation of E2 complexes is linked to cancers such as acute myeloid leukemia and to viral infections including hepatitis B [2,4,5].
• E2 complex activity is controlled by autoinhibition, autoubiquitination and dimerization, as shown for UBE2S [6,7].
• CRISPR knockout, point mutation, knock-in and overexpression models are essential to dissect E2 complex gene function in disease and development [1,2,4,8].
Description
The ubiquitin conjugating enzyme complex (GO:0031371), also known as the E2 complex, is a cellular component that possesses ubiquitin conjugating enzyme activity. It sits at the heart of the ubiquitin-proteasome system, where it receives activated ubiquitin from an E1 enzyme and transfers it to target proteins, often in concert with E3 ligases. This process controls protein stability, localization and interactions, and is fundamental to nearly every cellular pathway. Because E2 complexes determine substrate specificity and ubiquitin chain topology, they are intensively studied in cancer, virology and chromatin biology [1,2,4,5,6,7,8]. Recent work has expanded the known roles of E2 complexes beyond canonical proteolysis. For example, an E2 enzyme links diubiquitinated H2B to H3K27M oncohistone function, revealing a direct connection between ubiquitin conjugation and epigenetic regulation. In acute myeloid leukemia, UBE2N modulates proteostasis in immunoproteasome-positive cells, highlighting E2 complexes as potential therapeutic targets. UBE2O regulates hepatitis B virus maturation and egress, demonstrating that E2 complexes can be hijacked by viruses. These findings underscore why GO:0031371 is a critical annotation for researchers interpreting gene function and disease mechanisms. Understanding the composition, assembly and regulation of E2 complexes is therefore essential for experimental design. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a research-grade overview of GO:0031371, including its molecular mechanism, key genes, disease associations and CRISPR-based research methods.
ubiquitin conjugating enzyme complex At A Glance
| GO ID | GO:0031371 |
|---|---|
| GO term | ubiquitin conjugating enzyme complex |
| Ontology | cellular_component |
| Synonym | E2 complex |
| Definition | Any complex that possesses ubiquitin conjugating enzyme activity. |
| Major function | Ubiquitin transfer from E1 to substrate or E3 ligase |
| Related enzymes | UBE2C, UBE2N, UBE2O, UBE2S, Ubc11 |
| Disease relevance | Cancer, viral infection, proteostasis disorders |
What Is GO:0031371?
GO:0031371, the ubiquitin conjugating enzyme complex (synonym: E2 complex), is defined by QuickGO as any complex that possesses ubiquitin conjugating enzyme activity. In practical terms, it is a protein assembly containing one or more E2 enzymes that catalyze the transfer of ubiquitin from a thioester-linked E2-ubiquitin intermediate to a substrate, typically with the help of an E3 ligase. The complex may be a homodimer, heterodimer or a larger assembly, and its activity is regulated by post-translational modifications and protein-protein interactions [6,7].
Why Is ubiquitin conjugating enzyme complex Important in Cell Biology?
The ubiquitin conjugating enzyme complex is important because it is the central relay in the ubiquitin-proteasome system, determining which proteins are ubiquitinated and how. This controls protein degradation, signaling, DNA repair, cell cycle progression and immune responses. Dysregulation of E2 complexes contributes to cancer, viral pathogenesis and other diseases, making them attractive targets for therapeutic intervention and biomarkers [2,4,5].
• E2 complexes are essential for ubiquitin transfer and proteasomal degradation of key regulatory proteins.
• UBE2C is a potential cancer biomarker and is overexpressed in many tumors.
• UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.
• UBE2O regulates hepatitis B virus maturation and egress, linking E2 complexes to viral infection.
• UBE2S is regulated by autoinhibition and dimerization, affecting APC/C function [6,7].
• E2 enzymes can link ubiquitin signaling to chromatin modifications, as shown for H2B and H3K27M.
• Ubc11 regulates Rst2 protein stability in fission yeast, providing a model for E2 function.
• E2 complexes are involved in cell cycle control, apoptosis and DNA damage responses.
• Targeting E2 complexes is a promising strategy for cancer therapy [2,5].
• CRISPR screens can identify E2 complex vulnerabilities in disease models [1,2,4,8].
What Happens During ubiquitin conjugating enzyme complex?
Ubiquitin Activation and Transfer
In simple terms: Ubiquitin is passed like a baton from E1 to E2 to the target protein.
The ubiquitin conjugating enzyme complex functions in the ubiquitin-proteasome system by accepting ubiquitin from an E1 enzyme via a thioester bond and then transferring it to a substrate or E3 ligase. This multistep process ensures that ubiquitin is correctly attached to target proteins, often forming polyubiquitin chains that signal for proteasomal degradation or altered function.
Substrate Recognition and E3 Cooperation
In simple terms: E2 enzymes work with E3 ligases to choose which proteins get tagged.
E2 complexes do not act alone; they cooperate with E3 ubiquitin ligases to recognize specific substrates. The E3 ligase typically binds both the E2-ubiquitin conjugate and the substrate, facilitating ubiquitin transfer. Different E2-E3 pairs determine substrate specificity and ubiquitin chain topology, which in turn dictate the biological outcome.
Regulation by Autoinhibition and Autoubiquitination
In simple terms: E2 enzymes can shut themselves off by self-ubiquitination.
The activity of E2 complexes is tightly regulated. For example, UBE2S undergoes autoinhibition by autoubiquitination, which prevents excessive ubiquitin chain formation. This self-regulatory mechanism ensures that E2 activity is balanced and responsive to cellular needs.
Dimerization and Complex Assembly
In simple terms: E2 enzymes can pair up to change their function.
Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S, affecting its ability to build ubiquitin chains. This shows that the assembly state of E2 complexes is a key determinant of their catalytic activity and substrate specificity.
Key Genes Involved in GO:0031371 ubiquitin conjugating enzyme complex
The following genes encode E2 enzymes or components of ubiquitin conjugating enzyme complexes that have been experimentally linked to GO:0031371.
| Gene | Major Role | Research Relevance |
|---|---|---|
| UBE2C | Ubiquitin conjugating enzyme E2C | Potential cancer biomarker; overexpressed in tumors |
| UBE2N | Ubiquitin conjugating enzyme E2N | Modulates proteostasis in immunoproteasome-positive AML |
| UBE2O | Ubiquitin conjugating enzyme E2O | Regulates hepatitis B virus maturation and egress |
| UBE2S | Ubiquitin conjugating enzyme E2S | Autoinhibition and dimerization regulate APC/C function [6,7] |
| Ubc11 | Ubiquitin conjugating enzyme Ubc11 (fission yeast) | Regulates Rst2 protein stability |
| H2B | Histone H2B | Diubiquitinated H2B links to H3K27M oncohistone function |
| H3K27M | Oncohistone H3K27M | E2 enzyme links diubiquitinated H2B to H3K27M function |
| APC/C | Anaphase-promoting complex/cyclosome | E3 ligase complex associated with UBE2S |
| E1 | Ubiquitin-activating enzyme | Activates ubiquitin for transfer to E2 |
| E3 | Ubiquitin-protein ligase | Cooperates with E2 for substrate ubiquitination |
| Proteasome | 26S proteasome | Degrades ubiquitinated proteins |
| Rst2 | Transcription factor Rst2 | Regulated by Ubc11 in fission yeast |
| Immunoproteasome | Immunoproteasome complex | Associated with UBE2N in AML |
| HBV | Hepatitis B virus | Regulated by UBE2O |
| UBE2D | Ubiquitin conjugating enzyme E2D | General E2 enzyme in ubiquitin pathway |
| UBE2L3 | Ubiquitin conjugating enzyme E2L3 | General E2 enzyme in ubiquitin pathway |
How Is ubiquitin conjugating enzyme complex Regulated?
The ubiquitin conjugating enzyme complex is regulated at multiple levels. Autoinhibition by autoubiquitination controls UBE2S activity, preventing uncontrolled chain elongation. Dimerization of UBE2S further modulates its function in the APC/C pathway. Additionally, E2 enzymes can be regulated by interactions with E3 ligases, post-translational modifications and substrate availability. In disease contexts, UBE2N modulates proteostasis in immunoproteasome-positive AML, suggesting that cellular stress pathways influence E2 complex activity.
ubiquitin conjugating enzyme complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| UBE2C | Cancer biomarker and tumor progression | Knockout and overexpression in cancer cell lines |
| UBE2N | Acute myeloid leukemia proteostasis | Knockout in AML cell lines and primary cells |
| UBE2O | Hepatitis B virus maturation and egress | Knockout in HBV-infected hepatocytes |
| UBE2S | APC/C regulation and cell cycle | Point mutation and dimerization mutants [6,7] |
| Ubc11 | Fission yeast Rst2 stability | Knockout in Schizosaccharomyces pombe |
Cancer
E2 complexes are frequently dysregulated in cancer. UBE2C is a potential cancer biomarker and is overexpressed in many malignancies, where it promotes cell cycle progression and tumor growth. In acute myeloid leukemia, UBE2N modulates proteostasis in immunoproteasome-positive cells, supporting leukemia cell survival. The E2 enzyme linked to diubiquitinated H2B and H3K27M oncohistone function provides a direct link between ubiquitin conjugation and epigenetic drivers of pediatric gliomas.
Viral Infection
UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress. This demonstrates that viruses can exploit E2 complexes to complete their life cycle, and that targeting E2 enzymes may have antiviral therapeutic potential.
Proteostasis Disorders
Because E2 complexes are central to protein degradation, their dysfunction can lead to proteostasis disorders. UBE2N modulation of proteostasis in AML highlights how E2 enzymes maintain protein homeostasis in cancer cells. In fission yeast, Ubc11 regulates Rst2 protein stability, providing a model for studying E2-dependent proteostasis.
From ubiquitin conjugating enzyme complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of UBE2C affect tumor growth? | CRISPR knockout in cancer cell lines |
| How does UBE2N regulate proteostasis in AML? | Knockout and overexpression in AML cells |
| Does UBE2O control HBV egress? | Knockout in HBV-infected hepatocytes |
| How does UBE2S autoinhibition work? | Point mutation of autoubiquitination sites |
| What is the role of UBE2S dimerization? | Knock-in of dimerization mutants |
| How does Ubc11 regulate Rst2? | Knockout in fission yeast |
How to Study the ubiquitin conjugating enzyme complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene function loss | Identify essential E2 genes in cancer [2,5] |
| Point mutation | Specific residue function | Study UBE2S autoinhibition |
| Knock-in | Tagged or mutant protein expression | Track UBE2S dimerization |
| Overexpression | Gain-of-function effects | Model UBE2C overexpression in tumors |
| Proteomics | Ubiquitin chain topology and substrates | Map E2-E3-substrate networks |
| RNA-seq | Transcriptional changes | Analyze Ubc11 knockout in yeast |
| Co-immunoprecipitation | Protein-protein interactions | Detect E2-E3 complexes |
| Ubiquitination assays | Enzymatic activity | Measure E2 charging and transfer |
CRISPR Knockout Screens
CRISPR knockout screens can identify E2 complex genes required for cancer cell growth or viral infection. For example, knocking out UBE2C or UBE2N can reveal their essential roles in tumor cells [2,5]. These screens are powerful for discovering E2 vulnerabilities.
Proteomics and Ubiquitin Chain Analysis
Mass spectrometry-based proteomics can map ubiquitin chain topology and identify substrates of E2 complexes. This is critical for understanding how E2 enzymes like UBE2S build specific chains [6,7].
RNA-seq and Transcriptomics
RNA sequencing can measure transcriptional changes after E2 complex perturbation. For instance, Ubc11 knockout in fission yeast affects Rst2 target genes. This method links E2 function to gene expression programs.
Imaging and Localization Studies
Fluorescence microscopy can visualize E2 complex localization and dynamics. Tagged knock-in of UBE2S or UBE2N allows tracking of complex assembly and dimerization in live cells.
How CRISPR Can Be Used to Study GO:0031371 ubiquitin conjugating enzyme complex
Knockout
CRISPR knockout of E2 genes such as UBE2C or UBE2N can reveal their essential roles in cancer cell proliferation and survival [2,5]. Knockout models are also used to study viral maturation, as with UBE2O in hepatitis B virus.
Point Mutation
Point mutations can dissect specific residues required for E2 activity. For example, mutating autoubiquitination sites in UBE2S clarifies its autoinhibition mechanism. Such models are invaluable for structure-function studies.
Knock-in
Knock-in of tagged or mutant E2 enzymes allows tracking of complex assembly and dimerization. UBE2S dimerization mutants have been knocked in to study APC/C regulation. This approach preserves endogenous regulation.
Overexpression
Overexpression of E2 enzymes like UBE2C can model tumorigenesis and identify downstream effects. Overexpression models are also used to study UBE2N in AML proteostasis.
How EDITGENE Supports ubiquitin conjugating enzyme complex Research
Researchers studying ubiquitin conjugating enzyme complex-related genes often need to determine whether a candidate gene is causally involved in a specific disease or pathway. This requires precise genetic models that can knockout, mutate, tag or overexpress the gene of interest in relevant cell types. EDITGENE provides a comprehensive suite of CRISPR services to accelerate such studies.
Contact EDITGENE today to design your custom CRISPR model for ubiquitin conjugating enzyme complex research.
Frequently Asked Questions About ubiquitin conjugating enzyme complex
What is GO:0031371?
GO:0031371 is the Gene Ontology term for ubiquitin conjugating enzyme complex, a cellular component that possesses ubiquitin conjugating enzyme activity.
What is another name for ubiquitin conjugating enzyme complex?
The synonym for GO:0031371 is E2 complex.
What genes are involved in ubiquitin conjugating enzyme complex?
Key genes include UBE2C, UBE2N, UBE2O, UBE2S and Ubc11, among others [1,2,4,5,6,7,8].
How does the ubiquitin conjugating enzyme complex work?
It accepts ubiquitin from E1 and transfers it to substrates or E3 ligases, often forming polyubiquitin chains.
What diseases are linked to ubiquitin conjugating enzyme complex?
It is linked to cancers such as acute myeloid leukemia and to viral infections like hepatitis B [2,4,5].
How is UBE2S regulated?
UBE2S is regulated by autoinhibition via autoubiquitination and by dimerization [6,7].
What is the role of UBE2C in cancer?
UBE2C is a potential cancer biomarker and is overexpressed in many tumors.
How does UBE2O affect hepatitis B virus?
UBE2O regulates hepatitis B virus maturation and egress.
What model organisms are used to study E2 complexes?
Fission yeast Schizosaccharomyces pombe is used to study Ubc11 and Rst2 stability.
How can CRISPR help study ubiquitin conjugating enzyme complex?
CRISPR knockout, point mutation, knock-in and overexpression models enable functional dissection of E2 genes in disease [1,2,4,5,6,7,8].
Conclusion
The ubiquitin conjugating enzyme complex (GO:0031371) is a fundamental cellular component that drives ubiquitin transfer and controls protein fate. Its dysregulation is implicated in cancer, viral infection and proteostasis disorders, making it a high-priority target for research [2,4,5]. Advances in CRISPR-based models and bioinformatics are accelerating the discovery of E2 complex functions and therapeutic opportunities [1,2,4,8]. By leveraging precise knockout, point mutation, knock-in and overexpression models, researchers can dissect the roles of individual E2 enzymes and their complexes. EDITGENE provides end-to-end support for such studies, from library screening to bioinformatics, empowering the next generation of discoveries in ubiquitin biology.
References
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- 2. Ishikawa C et al.. 2025. Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.. J Clin Invest 135(10) PMID: 40371639
- 3. Liu W et al.. 2020. The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System.. Int J Mol Sci 21(8) PMID: 32326224
- 4. Lubyova B et al.. 2025. UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress.. J Biol Chem 301(11):110750 PMID: 40992660
- 5. Xie C et al.. 2014. Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker.. Int J Biochem Cell Biol 47:113-7 PMID: 24361302
- 6. Liess AKL et al.. 2019. Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination.. Structure 27(8):1195-1210.e7 PMID: 31230944
- 7. Liess AKL et al.. 2020. Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S.. Sci Signal 13(654) PMID: 33082289
- 8. Huang Y et al.. 2025. E2 ubiquitin-conjugating enzyme Ubc11 regulates Rst2 protein stability in the fission yeast Schizosaccharomyces pombe.. Arch Microbiol 207(11):275 PMID: 40982005
