URM1
null URM1 (ubiquitin-related modifier 1) is among the most ancient ubiquitin-like proteins, sharing a beta-grasp fold with ubiquitin and functioning at the interface of sulfur metabolism and protein modification. Activated by the dedicated E1-like enzyme UBA4 through its C-terminal glycine, URM1 is conjugated (urmylated) onto target proteins including peroxiredoxins, modulating their antioxidant activity and redox signaling. The same pathway donates sulfur for thiolation of wobble uridines in tRNA, linking URM1 to translational fidelity. Yeast lacking URM1 show hypersensitivity to oxidative stress, and the urmylation system is dysregulated in some cancers. Unlike ubiquitin chains, URM1 is not known to target proteins for proteasomal degradation, acting instead in redox and stress biology.
