A guide to UFMylation, an emerging posttranslational modification

David Millrine (Lead / Corresponding author), Joshua J. Peter (Lead / Corresponding author), Yogesh Kulathu (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)
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Ubiquitin Fold Modifier-1 (UFM1) is a ubiquitin-like modifier (UBL) that is posttranslationally attached to lysine residues on substrates via a dedicated system of enzymes conserved in most eukaryotes. Despite the structural similarity between UFM1 and ubiquitin, the UFMylation machinery employs unique mechanisms that ensure fidelity. While physiological triggers and consequences of UFMylation are not entirely clear, its biological importance is epitomized by mutations in the UFMylation pathway in human pathophysiology including musculoskeletal and neurodevelopmental diseases. Some of these diseases can be explained by the increased endoplasmic reticulum (ER) stress and disrupted translational homeostasis observed upon loss of UFMylation. The roles of UFM1 in these processes likely stem from its function at the ER where ribosomes are UFMylated in response to translational stalling. In addition, UFMylation has been implicated in other cellular processes including DNA damage response and telomere maintenance. Hence, the study of UFM1 pathway mechanics and its biological function will reveal insights into fundamental cell biology and is likely to afford new therapeutic opportunities for the benefit of human health. To this end, we herein provide a comprehensive guide to the current state of knowledge of UFM1 biogenesis, conjugation, and function with an emphasis on the underlying mechanisms.

Original languageEnglish
Pages (from-to)5040-5056
Number of pages17
JournalFEBS Journal
Issue number21
Early online date20 Jan 2023
Publication statusPublished - Nov 2023


  • Ubiquitin-like modifier
  • Endoplasmic reticulum
  • Proteostasis
  • protease
  • Ligase
  • UFM1
  • ligase
  • proteostasis
  • ubiquitin-like modifier
  • endoplasmic reticulum

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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