Alanyl-tRNA synthetase 1 (AARS1)

Alanyl-tRNA synthetase 1 (AARS1) is a highly conserved, essential enzyme responsible for ligating L-alanine to its cognate tRNA\(_{Ala}\) as a crucial step in cytoplasmic protein synthesis[1][5]. In addition to its canonical aminoacylation activity, AARS1 functions as a protein lactyltransferase: in the presence of high intracellular lactate, it can translocate to the nucleus and catalyze lysine lactylation on histone and non-histone proteins, thereby influencing processes such as cell proliferation, epigenetic regulation, and tumorigenesis by activating transcriptional complexes such as YAP-TEAD[3][5]. Pathogenic mutations in AARS1 gene are causally associated with Charcot-Marie-Tooth disease type 2N and, less commonly, trichothiodystrophy[1][4]. Elevated AARS1 expression has been implicated in poor prognosis in gastric cancer due to its role as a metabolic sensor and pro-proliferative factor[3][5]. There are currently no approved drugs directly targeting AARS1.

Other names

Alanine--tRNA ligase, cytoplasmicAARSAlaRSCMT2NProtein lactyltransferase AARS1Renal carcinoma antigen NY-REN-42DEE29EIEE29HDLS2TTD8alaRSalanine tRNA ligase 1, cytoplasmicalanyl-tRNA synthetasealanyl-tRNA synthetase, cytoplasmic

For protein synthesis: Catalyzes charging of tRNA with alanine using ATP. For lactyltransferase activity: Uses lactate and ATP to lactylate lysine residues on target proteins, altering their function (for example, activation of YAP-TEAD in cancer).