UBE2D1

Last update 08 May 2025

Basic Info

Synonyms

(E3-independent) E2 ubiquitin-conjugating enzyme D1, E2 ubiquitin-conjugating enzyme D1, E2(17)KB1

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Introduction

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:22496338). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:20061386). Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1 (PubMed:18042044, PubMed:18359941). Ubiquitinates STUB1-associated HSP90AB1 in vitro (PubMed:18042044). Lacks inherent specificity for any particular lysine residue of ubiquitin (PubMed:18042044). Essential for viral activation of IRF3 (PubMed:19854139). Mediates polyubiquitination of CYP3A4 (PubMed:19103148).

100 Clinical Results associated with UBE2D1

100 Translational Medicine associated with UBE2D1

0 Patents (Medical) associated with UBE2D1

323

Literatures (Medical) associated with UBE2D1

22 Apr 2025·Current Computer-Aided Drug Design

Targeting the Ubiquitin-conjugating Enzyme for Oral Squamous Cell Carcinoma Therapy: Discovering Natural Inhibitors

Article

Author: Misra, Krishna ; Soni, Unnati ; Varadwaj, Pritish Kumar

Background:Oral Squamous Cell Carcinoma (OSCC) is a multiple-phase carcinogenic disease that concurrently involves malignant lesions, invasion, and metastasis. It has been reported that Ubiquitin-conjugating enzymes play a significant role in the progression of OSCC and other fatal cancers through the process of ubiquitination. Among them, UBE2D1 represents a promising target for therapeutic intervention. Strategies aimed at inhibiting UBE2D1 could restore the function of tumor suppressors, such as p53, and potentially enhance the effectiveness of existing cancer therapies.Objective:This study aims to discover the potential natural inhibitors of UBE2D1 from an extensive chemical library through computational techniques.Methods:This study utilized in silico methods, such as virtual screening, molecular docking, analysis of pharmacokinetic parameters, and molecular dynamics simulation, to discover the most effective inhibitors for the ubiquitin-conjugating enzyme.Results:Based on binding affinity, the top six compounds, ZINC15113777, ZINC225461658, ZINC107430641, ZINC259440, ZINC4025306, and ZINC107283931, were found to be the best for the selected target. Also, molecular dynamic simulation results showed that all these compounds form stable complexes with UBE2D1.Conclusion:Based on our analysis of the results, we have determined that natural products, specifically ZINC15113777, ZINC4025306, and ZINC107283931, have the ability to inhibit UBE2D1 efficiently and could be utilized as potential drugs for the treatment of OSCC and other cancers. Such approaches may help to reinstate normal apoptotic pathways and improve overall treatment outcomes in patients with cancers characterized by UBE2D1 dysregulation. Additionally, conducting in-vitro/vivo studies on these molecules could be a prospective avenue in the realm of pharmaceutical research.

01 Feb 2025·Archives of Biochemistry and Biophysics

Molecular characterization of the E2 conjugating enzyme LinfUbc13 in Leishmania infantum

Article

Author: Teixeira, Felipe Roberti ; Zanchetta Venancio, Mayla Gabriela ; Torres, Caroline ; Santana Travaglini Berti de Correia, Camila Rolemberg ; de Oliveira de Castro, Taissa ; Rodrigues da Silva, Eduardo Vagner ; Nemamiah Escolarique Ribeiro, Hariel ; Abdel Baqui, Munira Muhammad ; da Costa Mancin, Giovanna ; Gomes, Marcelo Damário

UBC13 is an orthologue of Homo sapiens ubiquitin-conjugation E2 enzymes described in Leishmania mexicana, a null mutant lacking this gene cannot be produced, suggesting essential functions in this parasite. Leishmania infantum is an etiological agent of visceral leishmaniasis, the most severe type of disease that is potentially fatal if untreated. The ubiquitination process has been targeted for leishmanicidal compounds, indicating its essential function in parasite homeostasis. Therefore, the molecular characterization of the ubiquitination process may provide a better understanding of the molecular and cellular basis of leishmaniasis. Here, we characterized the gene LINF_350017900 in Leishmania infantum, which was named LinfUBC13, an E2 orthologue of UBC13 in Leishmania mexicana and the UBE2D family in Homo sapiens, sharing 72-74 % identity with UBE2D1, UBE2D2, and UBE2D3. LinfUbc13 contains conserved catalytic residues, including Cys86 and the HPN motif, which are essential for ubiquitin-conjugating activity. Structural analysis revealed a high similarity between LinfUbc13 and human UBE2D proteins, with a root-mean-square deviation (RMSD) of 0.4 Å, suggesting conserved functions. Recombinant LinfUbc13 was expressed and shown to accept ubiquitin from E1, forming a thioester intermediate. Functional assays demonstrated that LinfUbc13 transfers ubiquitin to p53 through human HDM2 E3 ligase, confirming its role in ubiquitination. Subcellular localization showed that LinfUbc13 was distributed throughout the parasite cytoplasm. These findings highlight the conserved nature of the ubiquitin-proteasome system between Leishmania infantum and Homo sapiens, showing that LinfUbc13 is an E2 enzyme that plays a crucial role in parasitic development.

07 Jan 2025·Proceedings of the National Academy of Sciences

Tsg101 mimicry of canonical E2 enzymes underlies its role in ubiquitin signaling

Article

Author: Carter, Carol A. ; Watanabe, Susan M. ; Nyenhuis, David A. ; Tjandra, Nico

Tsg101 is a highly conserved protein best known as an early-functioning component of cellular ESCRT machinery participating in recognition, sorting, and trafficking of cellular cargo to various intracellular destinations. It shares sequence and structural homology to canonical ubiquitin-conjugating (E2) enzymes and is linked to diverse events regulated by Ub signaling. How it might fulfill these roles is unclear. Here, we show that Tsg101 E2 mimicry permits interactions with diverse ubiquitin ligating (E3) enzymes and underlies its multifunctional capabilities. Coexpression of Tsg101 with the E3 ligase NNedd4-2s protected the enzyme from degradation and, remarkably, other widely divergent ligases as well. Structural alignment with UbcH5, a canonical E2 enzyme, revealed that recognition at the E2-E3 interface, a region broadly conserved despite sequence and structural differences in both E2 and E3 enzymes, was critical for protection. Nevertheless, UbcH5 failed to protect NNedd4-2s, indicating that the UEV chaperone function is unique to the variant. Studies using Cy5-Ub-VME showed that Tsg101-mediated protection reduced accessibility to Cys residues in the ligase. Access to Tsg101 Ub-binding sites was critical: Rabeprazole, which interferes with Tsg101 Ub-binding, diminished E3 ligase protection. Thus, E2 mimicry permitting control of E3 ligase ubiquitin signaling underlies Tsg101’s broad ability to participate in multiple cellular functions. The study provides mechanistic insight into how Tsg101, by partnering with diverse E3 ligases, can contribute to a broad range of cellular activities.

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UBE2D1

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