Ubiquitin-related modifier 1 (Urm1) is a unique and evolutionarily conserved member of the ubiquitin-like protein (UBL) family that represents a molecular link between ancestral sulfur carrier proteins (SCPs) and canonical eukaryotic UBLs. Urm1 is required for the thiolation of tRNAs and a non-canonical post-translational modification, called 'urmylation'. Activation of Urm1 by its E1-like enzyme, ubiquitin-like protein activator 4 (Uba4), involves the sequential adenylation, thioesterification, and thiocarboxylation of Urm1's C-terminus. Thereby, Urm1 can provide sulfur for the tRNA modification reaction or catalyze its conjugation to target proteins through a mechanism that is independent of E2-conjugating enzymes and E3 ligases. Recent structural studies have resolved several key intermediates of the fungal Uba4-Urm1 system, shedding light onto its two distinct subdomains and their dynamical interplay. Notably, Urm1 also interacts with several additional up- or downstream partners of the two pathways. Foremost, urmylation couples an UBL-conjugation reaction with the persulfidation of a cysteine residue in the target proteins. This protective oxidative post-translational modification underscores Urm1's central role in redox regulation and cellular stress responses. Here, we aim to summarize the most recent mechanistic insights and structural advances in the eukaryotic Urm1-Uba4 pathway.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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