ArticleJournal of molecular biology2019
An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 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
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- UFMylation in lipid metabolism disorders-associated diseases.Molecular biology reports · 2026Review
- Mechanistic basis for protein conjugation in a diverged bacterial ubiquitination pathway.Nature structural & molecular biology · 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
- Studies on the functional role of UFMylation in cells (Review).Molecular medicine reports · 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
- Allelic strengths of encephalopathy-associatedeLife · 2023Article
- Structural study of UFL1-UFC1 interaction uncovers the role of UFL1 N-terminal helix in ufmylation.EMBO reports · 2023Article
- Review
- Computed Protein-Protein Enthalpy Signatures as a Tool for Identifying Conformation Sampling Problems.Journal of chemical information and modeling · 2023Article
- Mechanistic insights into the roles of the UFM1 E3 ligase complex in ufmylation and ribosome-associated protein quality control.Science advances · 2023Article
- Genetic model of UBA5 deficiency highlights the involvement of both peripheral and central nervous systems and identifies widespread mitochondrial abnormalities.Brain communications · 2023Article
- A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation.The EMBO journal · 2022Article
- UFMylation System: An Emerging Player in Tumorigenesis.Cancers · 2022Review
- Overexpression of UBA5 in Cells Mimics the Phenotype of Cells Lacking UBA5.International journal of molecular sciences · 2022Article
- Structural basis for UFM1 transfer from UBA5 to UFC1.Nature communications · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.
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Registered trials
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.