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Target intelligence / Profile preview
Histidine—tRNA ligase (HisRS)
- Target
- HisRS
- Molecular classification
- Enzyme, Aminoacyl-tRNA synthetase, Class IIa aaRS
01
Overview
Histidine—tRNA ligase, also known as histidyl-tRNA synthetase (HisRS or HARS in humans), is an essential enzyme that catalyzes the attachment of the amino acid L-histidine to its corresponding tRNA (tRNA^His). This process is a critical step in protein biosynthesis, ensuring that histidine is correctly incorporated into growing polypeptide chains during translation. In humans, this enzyme is encoded by the HARS gene located on chromosome 5; it functions primarily in the cytoplasm. The human form (HARS) can be targeted by autoantibodies associated with autoimmune diseases such as polymyositis/dermatomyositis and myositis syndromes like anti-Jo–1 syndrome. These autoantibodies recognize epitopes on HARS/Jo–1 antigen leading to clinical manifestations related to these conditions.
- Other names
- Histidyl-tRNA synthetaseJo-1 antigenHistidyl-transfer ribonucleate synthetaseHistidine translaseHARS
02
Mechanism of action
Inhibition of Histidine-tRNA ligase activity.
03
Biological functions
AminoacylationProtein biosynthesistRNA chargingHistidine metabolism
04
Disease associations
Autoimmune diseasesPolymyositisDermatomyositisAnti-Jo-1 syndrome
05
Safety considerations
Potential for off-target effects due to the enzyme's essential role in protein synthesisDevelopment of resistance to inhibitorsAutoimmune response (anti-Jo-1 antibodies)
06
Biomarkers
Anti-Jo-1 antibodies
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