Isoleucine–tRNA ligase, cytoplasmic, also called isoleucyl-tRNA synthetase, cytoplasmic, is an enzyme that in humans is encoded by the IARS1gene (previously IARS). Like the related enzyme, IARS2, this enzyme functions as an isoleucine–tRNA ligase, meaning it attaches the amino acid isoleucine to its corresponding transfer RNA (tRNAIle) as part of protein synthesis.
Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Isoleucine-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family and has been identified as a target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Two alternatively spliced variants have been isolated that represent alternate 5' UTRs.
Pathogenic mutations in IARS1 (compound heterozygous) are the cause of a disorder associated with impaired physical and intellectual development, and sometimes liver disfunction, called GRIDHH (growth retardation, impaired intellectual development, hypotonia, and hepatopathy).
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