{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUFM1 is a recently discovered ubiquitin‐like modifier that is conjugated to target proteins via a dedicated “ufmylation” cascade. This pathway is initiated by the E1‐activating enzyme UBA5, relays through the E2 enzyme UFC1, and is executed in part by novel E3 ligases such as UFL1. Detailed biochemical and structural studies—including trans‐binding mechanisms that require UBA5 dimerization, specific interactions mediated by key residues (e.g., a defined UFM1 interacting sequence), and regulated ATP binding—reveal that the UFM1 system diverges from canonical ubiquitination. NMR and crystallographic analyses have further shown that the conformational plasticity of UFM1 and the oligomeric transitions of UBA5 underpin the efficiency and specificity of target modification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core enzymatic role, the UFM1 system is integral to maintaining cellular homeostasis. Ufmylation has been shown to regulate the function and structure of the endoplasmic reticulum (ER), ensuring proper protein quality control and efficient vesicle trafficking. Disruption of this pathway triggers ER stress and an enhanced unfolded protein response. In addition, ufmylation of proteins such as MRE11 is critical for the DNA damage response—facilitating efficient activation of ATM kinase, homologous recombination repair, and ultimately genome stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeregulation of ufmylation is increasingly implicated in human disease. Mutations in UBA5 and other components of the UFM1 cascade have been linked to severe neurological phenotypes and early‐onset encephalopathies, underscoring its importance in central nervous system development and neuronal function. In parallel, altered ufmylation contributes to tumorigenesis in various cancers—including breast, gastric, and oral squamous cell carcinomas—by modulating receptor coactivator stability, transcriptional activity, and downstream signaling pathways. Together, these findings emphasize the multifaceted role of UFM1 in ensuring cellular proteostasis and genome integrity while also delineating its involvement in disease pathogenesis, which may offer new avenues for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kanako Tatsumi, Yu-shin Sou, Norihiro Tada, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22147390"}], "href": "https://doi.org/10.3390/ijms22147390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34299007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34299007"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sebastian Fuchs, Alexey G Kikhney, Robin Schubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure and dynamics of UBA5-UFM1 complex formation showing new insights in the UBA5 activation mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Struct Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jsb.2021.107796"}], "href": "https://doi.org/10.1016/j.jsb.2021.107796"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34508858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34508858"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Manoj Kumar, Prasanth Padala, Jamal Fahoum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for UFM1 transfer from UBA5 to UFC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-25994-6"}], "href": "https://doi.org/10.1038/s41467-021-25994-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34588452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34588452"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Janine van Loon, Abbas Dehghan, Tang Weihong, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MRE11 UFMylation promotes ATM activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz110"}], "href": "https://doi.org/10.1093/nar/gkz110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30783677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30783677"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Zhi Fang, Zezheng Pan "}, {"type": "b", "children": [{"type": "t", "text": "Essential Role of Ubiquitin-Fold Modifier 1 Conjugation in DNA Damage Response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2019.4861"}], "href": "https://doi.org/10.1089/dna.2019.4861"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31368785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31368785"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Hee Min Yoo, Jong Ho Park, Jae Yeon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2022.0029"}], "href": "https://doi.org/10.14348/molcells.2022.0029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35680375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35680375"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Mikko Muona, Ryosuke Ishimura, Anni Laari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.06.020"}], "href": "https://doi.org/10.1016/j.ajhg.2016.06.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27545674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27545674"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Estelle Colin, Jens Daniel, Alban Ziegler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.06.030"}], "href": "https://doi.org/10.1016/j.ajhg.2016.06.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27545681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27545681"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ryosuke Ishimura, Miki Obata, Shun Kageyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel approach to assess the ubiquitin-fold modifier 1-system in cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.12518"}], "href": "https://doi.org/10.1002/1873-3468.12518"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27926783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27926783"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Macarena Cabrera-Serrano, David Joseph Coote, Dimitar Azmanov, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2022.111168"}], "href": "https://doi.org/10.1016/j.celrep.2022.111168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35926457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35926457"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Chin Ha Chung, Hee Min Yoo "}, {"type": "b", "children": [{"type": "t", "text": "Emerging role of protein modification by UFM1 in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.08.093"}], "href": "https://doi.org/10.1016/j.bbrc.2022.08.093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36344165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36344165"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Misha Mao, Yongxia Chen, Jingjing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunother Cancer (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jitc-2022-005668"}], "href": "https://doi.org/10.1136/jitc-2022-005668"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36543379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36543379"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Di Ke, Hao-Han Guo, Ni Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.205219"}], "href": "https://doi.org/10.18632/aging.205219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37980168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37980168"}]}]}]}