Tryptophan–tRNA ligase, cytoplasmic, also called Tryptophanyl-tRNA synthetase 1, is an enzyme that in humans is encoded by the WARS1 gene (previously WARS). As a tryptophan–tRNA ligase, it attaches the amino acid tryptophan to its cognate tRNA.
Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS1, and a mitochondrial form, named WARS2. WARS1 catalyzes the aminoacylation of tRNATrp with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene.
Phenylalanine incorporation Although WARS1 classically aminoacylates tryptophan, but during states of tryptophan depletion, it has been observed activating both tryptophan and phenylalanine.
Medical significance Pathogenic (heterozygous) mutations in WARS1 are associated with dysfunction of the motor neurons leading to progressive muscle weakness and atrophy of the arms and legs, called autosomal dominant distal hereditary motor neuronopathy-9 (HMND9).
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