Threonyl-tRNA synthetase 1 (TARS1)

Threonyl-tRNA synthetase 1 (TARS1) is a cytoplasmic enzyme responsible for catalyzing the attachment of threonine to its corresponding tRNA (tRNA^Thr) in two steps: activating threonine with ATP and transferring it to tRNA, a process essential for protein synthesis[1][3][6]. TARS1 is a member of the class II aminoacyl-tRNA synthetase family and additionally possesses an editing function to prevent mischarging of tRNA with serine[2][3]. Beyond its canonical role in translation, TARS1 has significant non-translational (non-canonical) functions, including regulation of gene expression, angiogenesis—by acting as a secreted signaling molecule in endothelial cells, influencing vascular development—and the modulation of myogenic differentiation via JNK signaling in muscle cells[2]. Mutations in TARS1 are associated with genetic diseases like trichothiodystrophy 7, and aberrant expression has roles in cancer and inflammation[1][2][5][7]. Borrelidin, a natural product inhibitor, blocks TARS1 activity and suppresses angiogenesis, providing a pharmacological tool to study its therapeutic targeting, though inhibition can also cause toxicity linked to global inhibition of protein synthesis[2].

Other names

Threonine--tRNA ligase 1, cytoplasmicTARSThrRSThreonyl-tRNA synthetasethreonine tRNA ligase 1, cytoplasmicTTD7

Competitive inhibition of threonine binding to TARS1 active site (borrelidin); Induction of amino acid starvation response; Modulation of angiogenic signaling.