ArticleNature communications2022
The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 84 citations in OpenAlex.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- Divergence of the CYB5R3-mARC1 Redox Axis Across the Human MASLD-to-Hepatocellular-Carcinoma Continuum: An Exploratory Analysis of Liver-Biopsy and Tumor Cohorts.International journal of molecular sciences · 2026Article
- 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
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- UFL1-Mediated UFMylation of ENO1 Restrains Aerobic Glycolysis and Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systematic discovery of UFM1 receptors reveals a regulatory module in DNA repair directing non-homologous end-joining.Nature communications · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- The UFSP2-C1orf27 complex positions nascent GPCRs to the ufmylation system for ER export control.iScience · 2026Article
- Btg2 inhibits Fmo1 UFMylation thus exacerbating ferroptosis and apoptosis in hepatic ischemia-reperfusion injury.Nature communications · 2026Article
- The ubiquitin-like protein FAT10 enhances the autophagy-mediated degradation of ZO-1 by stabilizing ATG3 to promote the lung metastasis of colon cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A severe neurodevelopmental syndrome linked to a South Asian founder variant in the UFMylation adaptor CDK5RAP3.Acta neuropathologica · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- Optimization of protein UFMylation modification method and its application in substrate identification in human cells.The Journal of biological chemistry · 2026Article
- Ufmylation-Deficient DDRGK1 Ameliorates Obesity by Inhibiting FASN-Mediated Adipocyte Lipogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026Article
- A genus-wide interaction atlas across NS4B orthologues identifies a conserved role for UFMylation in orthoflavivirus replication.Nature communications · 2026Article
- Core principles of autophagy initiation mechanisms.Nature structural & molecular biology · 2026Review
- Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026Review
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein modification by ubiquitin-like proteins (UBLs) amplifies limited genome information and regulates diverse cellular processes, including translation, autophagy and antiviral pathways. Ubiquitin-fold modifier 1 (UFM1) is a UBL covalently conjugated with intracellular proteins through ufmylation, a reaction analogous to ubiquitylation. Ufmylation is involved in processes such as endoplasmic reticulum (ER)-associated protein degradation, ribosome-associated protein quality control at the ER and ER-phagy. However, it remains unclear how ufmylation regulates such distinct ER-related functions. Here we identify a UFM1 substrate, NADH-cytochrome b5 reductase 3 (CYB5R3), that localizes on the ER membrane. Ufmylation of CYB5R3 depends on the E3 components UFL1 and UFBP1 on the ER, and converts CYB5R3 into its inactive form. Ufmylated CYB5R3 is recognized by UFBP1 through the UFM1-interacting motif, which plays an important role in the further uyfmylation of CYB5R3. Ufmylated CYB5R3 is degraded in lysosomes, which depends on the autophagy-related protein Atg7- and the autophagy-adaptor protein CDK5RAP3. Mutations of CYB5R3 and genes involved in the UFM1 system cause hereditary developmental disorders, and ufmylation-defective Cyb5r3 knock-in mice exhibit microcephaly. Our results indicate that CYB5R3 ufmylation induces ER-phagy, which is indispensable for brain development.
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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.