UBE2N Human
Description
Introduction to UBE2N Human
UBE2N (Ubiquitin-conjugating enzyme E2 N), encoded by the UBE2N gene, is a critical component of the ubiquitination machinery. It facilitates the synthesis of Lys-63-linked polyubiquitin chains in conjunction with E3 ligases, directing non-proteolytic signaling rather than protein degradation . This protein is essential for DNA repair, immune responses, and cell cycle regulation.
Key Features:
| Property | Description |
|---|---|
| Gene Location | Human chromosome 12 |
| Protein Interactions | HLTF, TRAF2, TRAF6, UBE2V1, AURKA, RNF5, TRIM21 |
| Functional Partners | UBE2V1/V2 heterodimers for K63-linked chain synthesis |
| Biological Roles | DNA post-replication repair (PRR), NF-κB activation, viral restriction, AD pathology |
DNA Repair and Genotoxic Stress
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Post-replication repair (PRR): Collaborates with HLTF and SHPRH to polyubiquitinate PCNA, enabling error-free DNA repair .
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DNA damage response (DDR): Synthesizes K63-linked chains at sites of double-strand breaks (DSBs), promoting repair via BRCA1-CtIP and 53BP1 pathways .
Immune and Inflammatory Signaling
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Antiviral defense: UBE2N-UBE2V1 heterodimers activate RIG-I and TRIM5, triggering interferon β production and NF-κB-mediated inflammation .
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Immune cell regulation: Modulates TRAF6 ubiquitination in IL-17A signaling and T-cell receptor pathways .
Role in Alzheimer’s Disease (AD)
UBE2N has emerged as a novel biomarker and therapeutic target in AD:
Key Findings:
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AD Biomarker Potential: UBE2N expression is downregulated in CD4+ T cells of AD patients and correlates with synaptic vesicle cycling .
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Therapeutic Targeting: Pharmacological inhibition reduces Aβ pathology in 5×FAD mice, suggesting a pathway for AD intervention .
Implications in Cancer
UBE2N is a druggable target in hematologic malignancies:
Acute Myeloid Leukemia (AML)
Critical Insights:
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Catalytic dependency: UBE2N’s C87 residue is essential for AML survival but not normal hematopoiesis .
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TRIM21 dependency: TRIM21 depletion phenocopies UBE2N inhibition, highlighting a therapeutic axis .
DNA Damage Response in Solid Tumors
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Synthetic lethality: UBE2N inhibition sensitizes G-quadruplex (G4)-stabilized cancers to replication stress, offering combinatorial therapeutic potential .
Table 1: UBE2N Interactions and Functional Partners
Table 2: AD-Related UBE2N Findings
Product Specs
Ubiquitin-conjugating enzyme E2 N, Bendless-like ubiquitin-conjugating enzyme, Ubc13, Ubiquitin carrier protein N, Ubiquitin-protein ligase N, UBE2N, BLU, MGC8489, UbcH-ben, MGC131857.
Product Science Overview
Ubiquitin Conjugating Enzyme E2N (UBE2N), also known as UBC13, is a crucial component of the ubiquitination pathway, which is a post-translational modification process that regulates protein degradation and various cellular functions. UBE2N is a member of the E2 ubiquitin-conjugating enzyme family and plays a significant role in the synthesis of non-canonical ‘Lys-63’-linked polyubiquitin chains .
UBE2N, in conjunction with its co-factors UBE2V1 and UBE2V2, catalyzes the formation of ‘Lys-63’-linked polyubiquitin chains. Unlike the more common ‘Lys-48’-linked chains that target proteins for degradation by the proteasome, ‘Lys-63’-linked chains are involved in various cellular processes, including DNA repair, signal transduction, and immune response . This type of polyubiquitination does not lead to protein degradation but rather mediates transcriptional activation of target genes and plays a role in cell cycle control and differentiation .
UBE2N is essential for the error-free DNA repair pathway and contributes to cell survival following DNA damage. It is involved in the Toll-Like Receptor (TLR) signaling pathway and the homologous recombination repair (HRR) or single-strand annealing (SSA) pathways . The enzyme’s activity is crucial for maintaining genomic stability and proper cellular function.
Human recombinant UBE2N is typically produced using recombinant DNA technology. The gene encoding UBE2N is cloned into an expression vector, which is then introduced into a suitable host cell, such as Escherichia coli or yeast. The host cells are cultured under conditions that promote the expression of the UBE2N protein. After expression, the protein is purified using various chromatographic techniques to obtain a highly pure and functional enzyme.
UBE2N participates in the ubiquitination process by transferring activated ubiquitin from the E1 ubiquitin-activating enzyme to the substrate protein, with the help of an E3 ubiquitin ligase. The enzyme’s activity can be analyzed using in vitro ubiquitination assays, where the formation of polyubiquitin chains is monitored. Additionally, mass spectrometry and Western blotting are commonly used to study the enzyme’s function and interaction with other proteins.
Mutations or dysregulation of UBE2N have been associated with various diseases, including certain types of cancer and neurodegenerative disorders. Understanding the enzyme’s function and regulation can provide insights into potential therapeutic targets for these conditions.
