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Target intelligence / Profile preview
Isoleucyl-tRNA synthetase 1 (IARS1)
- Target
- IARS1
- Molecular classification
- Enzyme, Aminoacyl-tRNA synthetase (Class I family)
01
Overview
Isoleucyl-tRNA synthetase 1 (IARS1) is a cytoplasmic class I aminoacyl-tRNA synthetase that catalyzes the ATP-dependent ligation of isoleucine to its corresponding tRNA, ensuring accurate protein synthesis. IARS1 contains catalytic, tRNA-binding, CP2 and zinc finger domains, as well as editing and regulatory regions. Its non-translational roles include regulating DNA repair via nuclear interaction with BRCA1 and stabilization of multi-synthetase complexes. Mutations in IARS1 are linked to metabolic, growth, and neurological disorders, and the protein serves as a target for antibacterial agents (such as mupirocin). It is also implicated as an autoantigen in certain immune-mediated diseases.
- Other names
- Isoleucine--tRNA ligase, cytoplasmicIARSIRSIleRSILRSIsoleucyl-tRNA synthetaseIsoleucine tRNA ligase 1, cytoplasmicGRIDHHILERSPRO07852510016L12RIKE430001P04RIKIarslOJLOC103690033
02
Mechanism of action
Inhibition of aminoacyl-tRNA synthetase activity, blocking protein synthesis (mupirocin, reveromycin A)
03
Biological functions
Protein synthesis (attachment of isoleucine to tRNA)Regulation of DNA repair (interaction with BRCA1)Protects multi-synthetase complex proteins from degradationNon-translational signaling via protein-protein interactions
04
Disease associations
Autoimmune diseases (e.g., polymyositis/dermatomyositis)Growth retardation, impaired intellectual development, hypotonia, and hepatopathyCombined oxidative phosphorylation deficiency
05
Safety considerations
Mutations can cause mitochondrial dysfunction, growth impairment, intellectual disability, hypotonia, hepatopathyOff-target effects of inhibitors may impact protein synthesis in non-bacterial cells
06
Interacting drugs
Mupirocin (antibiotic targeting bacterial IleRS)
1 more in the full profile.
07
Biomarkers
Autoantibodies against IARS1 in autoimmune myositis/dermatomyositisGenetic mutations in IARS1 are diagnostic for specific metabolic and neurodevelopmental syndromes
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