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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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URM1
ubiquitin related modifier 1
Chromosome 9 · 9q34.11
NCBI Gene: 81605Ensembl: ENSG00000167118.12HGNC: HGNC:28378UniProt: Q9BTM9
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsulfur carrier activitytRNA wobble uridine modificationtRNA thio-modificationneurodegenerative diseasespinal cord injurytype 2 diabetes mellitusobesity
✦AI Summary

URM1 (ubiquitin related modifier 1) functions as both a sulfur carrier protein and an ubiquitin-like modifier, representing an evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins 1. As a sulfur carrier, URM1 is essential for 2-thiolation of mcm(5)S(2)U at wobble positions of cytosolic tRNAs (tRNA-Lys, tRNA-Glu, and tRNA-Gln) through thiocarboxylation at its C-terminus by MOCS3, followed by sulfur transfer to tRNA 2. Additionally, URM1 acts as an ubiquitin-like protein that undergoes covalent conjugation to lysine residues of target proteins including MOCS3, ATPBD3, CTU2, USP15, and CAS through a process called urmylation 1. This dual functionality is mediated by the E1-like enzyme Uba4, which activates URM1 through sequential adenylation, thioesterification, and thiocarboxylation 3. Urmylation is enhanced by oxidative stress and involves coupling UBL-conjugation with persulfidation of cysteine residues in target proteins, highlighting URM1's central role in redox regulation and cellular stress responses 3. The thiocarboxylated form serves as substrate for both tRNA thiolation and protein conjugation, making URM1 unique among ubiquitin-like proteins in its ability to participate in both RNA and protein modification pathways 4.

Sources cited
1
URM1 has dual role as protein modifier and sulfur carrier, evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins
PMID: 21904977
2
URM1 functions as sulfur carrier in tRNA thiolation and can be conjugated to proteins like Ahp1p
PMID: 19047990
3
URM1 activation by Uba4 involves adenylation, thioesterification, and thiocarboxylation; urmylation couples with persulfidation for redox regulation
PMID: 41700452
4
URM1 targets multiple proteins and participates in both RNA and protein modification pathways
PMID: 33548388
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
spinal cord injuryOpen Targets
0.16Weak
type 2 diabetes mellitusOpen Targets
0.13Weak
obesityOpen Targets
0.10Weak
MODYOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.07Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
type 1 diabetes mellitusOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.05Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
diabetes mellitus, permanent neonatal 4Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 2Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
maturity-onset diabetes of the young type 13Open Targets
0.04Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.04Suggestive
permanent neonatal diabetes mellitus 1Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KTI12Shared pathway100%MPSTProtein interaction100%TSTProtein interaction100%NFS1Protein interaction100%ELP3Protein interaction100%GABARAPL1Protein interaction95%
Tissue Expression6 tissues
Heart
100%
Liver
83%
Bone Marrow
80%
Lung
77%
Ovary
69%
Brain
64%
Gene Interaction Network
Click a node to explore
URM1KTI12MPSTTSTNFS1ELP3GABARAPL1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BTM9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.99LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.58 [0.36–0.99]
RankingsWhere URM1 stands among ~20K protein-coding genes
  • #12,913of 20,598
    Most Researched26
  • #9,446of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedURM1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Ubiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism.
PMID: 28234446
Chem Rev · 2018
1.00
2
The emerging roles of ubiquitin-like protein Urm1 in eukaryotes.
PMID: 33548388
Cell Signal · 2021
0.90
3
Structural insights into the Urm1-Uba4 pathway and its biological roles.
PMID: 41700452
Essays Biochem · 2025
0.80
4
HYPK coordinates degradation of polyneddylated proteins by autophagy.
PMID: 34836490
Autophagy · 2022
0.70
5
The dual role of ubiquitin-like protein Urm1 as a protein modifier and sulfur carrier.
PMID: 21904977
Protein Cell · 2011
0.60