ArticleThe Journal of biological chemistry2014
Mechanistic study of Uba5 enzyme and the Ufm1 conjugation pathway.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- Adjunctive nebulization of Idursulfase to intravenous treatment enhances cardiac proteome adaptations in IDS-KO mice.bioRxiv : the preprint server for biology · 2026Article
- Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression.Signal transduction and targeted therapy · 2026Article
- Review
- The coordinated action of UFMylation and the RQC pathways clears arrested polypeptides at the ER.The EMBO journal · 2026Article
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- Multifaceted roles of UFMylation in health and disease.Acta pharmacologica Sinica · 2025Review
- Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin.Medicines (Basel, Switzerland) · 2025Article
- A novel compound heterozygous mutation of UFC1 in a patient with neurodevelopmental disorder.Genes & genomics · 2024Article
- Allelic strengths of encephalopathy-associatedeLife · 2023Article
- Comparative Proteomics and Genome-Wide Druggability Analyses Prioritized Promising Therapeutic Targets against Drug-ResistantMicroorganisms · 2023Article
- UFMylation System: An Emerging Player in Tumorigenesis.Cancers · 2022Review
- Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles.Cell structure and function · 2022Review
- Structural basis for UFM1 transfer from UBA5 to UFC1.Nature communications · 2021Article
- Inhibition of UBA5 Expression and Induction of Autophagy in Breast Cancer Cells by Usenamine A.Biomolecules · 2021Article
- A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1.International journal of molecular sciences · 2021Article
- Highly Specialized Ubiquitin-Like Modifications: Shedding Light into the UFM1 Enigma.Biomolecules · 2021Review
- UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
E1 enzymes activate ubiquitin or ubiquitin-like proteins (Ubl) via an adenylate intermediate and initiate the enzymatic cascade of Ubl conjugation to target proteins or lipids. Ubiquitin-fold modifier 1 (Ufm1) is activated by the E1 enzyme Uba5, and this pathway is proposed to play an important role in the endoplasmic reticulum (ER) stress response. However, the mechanisms of Ufm1 activation by Uba5 and subsequent transfer to the conjugating enzyme (E2), Ufc1, have not been studied in detail. In this work, we found that Uba5 activated Ufm1 via a two-step mechanism and formed a binary covalent complex of Uba5∼Ufm1 thioester. This feature contrasts with the three-step mechanism and ternary complex formation in ubiquitin-activating enzyme Uba1. Uba5 displayed random ordered binding with Ufm1 and ATP, and its ATP-pyrophosphate (PPi) exchange activity was inhibited by both AMP and PPi. Ufm1 activation and Uba5∼Ufm1 thioester formation were stimulated in the presence of Ufc1. Furthermore, binding of ATP to Uba5∼Ufm1 thioester was required for efficient transfer of Ufm1 from Uba5 to Ufc1 via transthiolation. Consistent with the two-step activation mechanism, the mechanism-based pan-E1 inhibitor, adenosine 5'-sulfamate (ADS), reacted with the Uba5∼Ufm1 thioester and formed a covalent, tight-binding Ufm1-ADS adduct in the active site of Uba5, which prevented further substrate binding or catalysis. ADS was also shown to inhibit the Uba5 conjugation pathway in the HCT116 cells through formation of the Ufm1-ADS adduct. This suggests that further development of more selective Uba5 inhibitors could be useful in interrogating the roles of the Uba5 pathway in cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.