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Seryl-tRNA synthetase 2, mitochondrial (SARS2)
- Target
- SARS2
- Molecular classification
- Enzyme, Aminoacyl-tRNA synthetase, Class II tRNA synthetase
01
Overview
Seryl-tRNA synthetase 2, mitochondrial (SARS2) is a class II aminoacyl-tRNA synthetase enzyme localized in mitochondria, responsible for charging mitochondrial tRNAs with serine—specifically tRNA Ser(AGY) and tRNA Ser(UCN)—as part of the mitochondrial translation machinery[2][4]. The enzyme works as a homodimer; it consists of an N-terminal tRNA binding domain and a catalytic core domain[4]. Variants in the SARS2 gene impair tRNA binding and aminoacylation, leading to selective degradation of mitochondrial tRNA Ser(AGY), and causing profound translation defects and cellular energy imbalance[1][2]. SARS2 dysfunction is linked to mitochondrial diseases such as HUPRA syndrome and progressive spastic paresis, with clinical presentations ranging from early embryonic lethality to multisystem disorders[1][2]. There are multiple transcript variants, and its gene regulation is linked to nearby mitochondrial ribosomal protein genes[4]. SARS2 is not a known direct drug target, but its mutations serve as biomarkers for disease diagnosis.
- Other names
- Serine--tRNA ligase, mitochondrialSARS2SARSMSerRSFLJ20450mtSerRSSerRSmtSARSSERSSYSSeryl-tRNA synthetaseSeryl-tRNA(Ser/Sec) synthetaseserine tRNA ligase 2, mitochondrialmitochondrial seryl-tRNA synthetase
02
Biological functions
Protein synthesis/translationAminoacylation of tRNAMitochondrial translationCellular energy homeostasis
03
Disease associations
Multisystem mitochondrial diseaseHUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure, and alkalosis)Progressive spastic paresisMitochondrial dysfunction
04
Safety considerations
Genetic variants can cause severe mitochondrial dysfunction and multi-organ disease[1][2].Mutations can result in early embryonic fatality and tissue-specific mitochondrial deficits[2].
05
Biomarkers
Mutations in SARS2 gene (e.g., c.1169A > G, c.667G > A, c.1031G > A, c.1205G > A, c.1347G > A, c.1343A > T, c.654-14T > A, c.1519dupC)[2].tRNA charging levels and abundance of mitochondrial tRNA Ser(AGY)[1][2]
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