Ask about this productRelated genes to: URM1 antibody
- Gene:
- URM1 NIH gene
- Name:
- ubiquitin related modifier 1
- Previous symbol:
- C9orf74
- Synonyms:
- MGC2668
- Chromosome:
- 9q34.11
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-06
- Date modifiied:
- 2016-10-05
Related products to: URM1 antibody
Related articles to: URM1 antibody
- Ubiquitin-like proteins (Ubls) such as SUMO, NEDD8, ISG15, URM1, UFM1, FAT10, ATG8/ATG12, and FUBI are essential regulators of cellular homeostasis, controlling processes from protein stability and trafficking to immune signaling and autophagy. Their conjugation-deconjugation cycles are mediated by cascades of E1, E2, and E3 enzymes and reversed by Ubl-specific proteases (ULPs), many of which are cysteine-dependent. Deciphering these dynamic and reversible pathways requires tools that directly capture the active forms of these enzymes. Activity-based probes (ABPs) have become indispensable for this task, providing covalent, mechanism-based snapshots of enzymatic activity in complex systems. This review highlights chemistry-centric strategies for the design and synthesis of Ubl-targeting ABPs. We summarize synthetic and semisynthetic approaches that install electrophilic warheads onto Ubl backbones, methods for C-terminal ligation (native chemical ligation, activated cysteine ligation, hydrazide chemistry), and strategies for incorporating reporter tags or bioorthogonal handles. Probe development is organized by target class, including Ubl isopeptidases, E1/E2 conjugating enzymes, and E3 ligases. Representative examples illustrate how chemical design choices are tailored for specific applications-ranging from live-cell activity profiling to proteomic mapping and inhibitor discovery. Together, these methodologies establish a versatile chemical toolkit for dissecting Ubl biology, enabling the discovery of novel enzymes, the mapping of substrate networks, and the development of potential therapeutic modulators. - Source: PubMed
Publication date: 2026/02/23
Chanda SaibalPham AlanKarnati SreeNidhiRodriguez Natalia SotoToner AlyssaLiu Wenshe Ray - 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. - Source: PubMed
Kwasna DominikaRavichandran Keerthiraju EBiela AnnaGlatt Sebastian - Ubiquitin (Ub) and ubiquitin-like proteins (Ubls) orchestrate diverse cellular processes through reversible post-translational modification of target proteins. Their conjugation is governed by a cascade of E1 activating, E2 conjugating, and E3 ligating enzymes, while deconjugation is mediated by deubiquitinases (DUBs) and Ubl-specific proteases. Profiling the catalytic activity of these enzymes is essential for understanding the dynamics and specificity of Ub/Ubl signaling. Activity-based probes (ABPs) have emerged as powerful tools to covalently label active enzymes through electrophilic warheads that target catalytic residues. Unlike conventional affinity-based approaches, ABPs capture functional states of enzymes in complex biological systems. This review provides a comprehensive analysis of ABPs designed for the Ub/Ubl signal pathways, encompassing probes for Ub, SUMO, NEDD8, ISG15, FAT10, UFM1, URM1, Atg8-family modifiers, and FUBI (MNSFβ). We discuss key elements of probe design, including recognition domains, electrophilic warheads (e.g., vinyl sulfones, vinyl methyl esters, propargylamine, azapeptide esters), and detection tags. Particular emphasis is placed on emerging azapeptide ester-based probes, which structurally mimic native enzyme-substrate intermediates and offer high selectivity and reactivity. ABPs targeting E1, E2, and HECT/RBR E3 ligases are also highlighted, expanding their utility beyond classical DUB profiling. We further compare warhead chemistries, enzyme selectivity, and labeling strategies, and examine structural insights derived from probe-enzyme complexes. Collectively, these tools have transformed our ability to interrogate Ub/Ubl-regulating enzymes in vitro and in cells. The review concludes with perspectives on next-generation probe development, including cell-permeable designs, spatiotemporal control, and applications in systems biology and drug discovery. - Source: PubMed
Publication date: 2026/02/11
Chanda SaibalLiu Wenshe Ray - Urm1 from yeast is a unique ubiquitin-like protein with dual functionality. It has been shown to operate in tRNA thiolation and protein urmylation, combining features typical of bacterial sulfur carriers and classical ubiquitin-like modifiers. Hence, in evolutionary terms, Urm1 may be placed at the crossroad of prokaryotic sulfur transfer and eukaryotic protein conjugation pathways. Prompted by Urm1-like proteins identified in Archaea, we examined Urm1 functional conservation using URM1 gene shuffle from Sulfolobus acidocaldarius to Saccharomyces cerevisiae. We find that archaeal Urm1 conjugates to peroxiredoxin Ahp1, a bona fide urmylation target in yeast, but cannot support tRNA thiolation. Ahp1 conjugation requires sulfur transfer onto the archaeal Urm1 modifier from Uba4, the E1-like urmylation activator in yeast. Thus, thioactivation of archaeal Urm1 and urmylation-like conjugation are conserved and exchangeable processes between Sulfolobus and Saccharomyces. Our survey underlines that Urm1 likely occupies a key role in the evolution of the ubiquitin-like protein family. - Source: PubMed
Publication date: 2025/11/23
Zupfer KatharinaKaduhr LarsBessler LarissaHelm MarkSchaffrath Raffael - Although homologs of the eukaryotic Urm1 (ubiquitin-related modifier-1) have been characterized in Archaea, the substrates and roles of the archaeal Urm1 remain poorly understood. Here, we report a proteomic analysis of Urm1 modification in using a highly efficient method, which involves the introduction of an H81R substitution into Urm1 encoded by the strain, treatment of the strain with the proteasome inhibitor bortezomib, and affinity enrichment of urmylated peptides with an anti-K-ε-Gly-Gly antibody following peptide fractionation. Extensive protein urmylation was observed, with a total of 783 Urm1 conjugation sites, mapped to 330 proteins, identified in the cell. Among the seven lysine residues in Urm1, six were sites of modification, of which K7 and K37 were preferentially modified. Treatment with the proteasome inhibitor bortezomib resulted in K37-linked chains being the sole major modification species, suggesting that K37 linkage served as a primary trigger of proteasomal degradation. The modified proteins were involved in a number of cellular processes, such as cell division, chromosomal organization, DNA replication, translation, proteasomal protein degradation, and sulfur relay. Protein urmylation was dynamic and influenced by growth conditions and stress treatments. Attempts to delete were unsuccessful, pointing to the essentiality of the gene. The knockdown of resulted in substantial growth delay, during which a drastic reduction in cellular concentration of cell division proteins (CdvB, CdvB1, CdvB2) occurred. Our results shed significant light on the landscape and potential roles of protein urmylation in Archaea.IMPORTANCEAlthough protein urmylation has been documented in Archaea for over a decade, the authentic substrates and functional roles of archaeal Urm1 remain largely unknown. In this study, we generated the largest Urm1 modification data set in Archaea through an efficient approach and investigated its physiological functions in . Extensive protein urmylation was observed, with modified proteins implicated in key cellular processes such as cell division, chromosomal organization, translation, and proteasomal degradation. Our findings challenge the prevailing notion that Urm1 homologs modify only a limited number of substrates. Six out of seven lysine residues in Urm1 were modified, suggesting the presence of diverse Urm1 chain structures. These results provide cellular evidence supporting the hypothesis that eukaryotic Ub/Ubl systems have an archaeal origin. We also explored how various factors affect global protein urmylation and examined the impact of knockdown on cell growth. - Source: PubMed
Publication date: 2025/10/20
Cao JingjingXiong DaijiangZheng XiaoweiYuan WanjuanHuang Li