AARS1

Alanyl—tRNA synthetase 1 (AARS1) is an enzyme that is encoded by the AARS1 gene in humans and is a member of the aminoacyl-tRNA synthetases (ARSs) family of enzymes.^[5]

AARS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4XEO, 4XEM
Identifiers
Aliases	AARS1, CMT2N, EIEE29, alanyl-tRNA synthetase, AARS, alanyl-tRNA synthetase 1, DEE29, TTD8, HDLS2
External IDs	OMIM: 601065; MGI: 2384560; HomoloGene: 1213; GeneCards: AARS1; OMA:AARS1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q22.1 Start 70,251,983 bp[1] End 70,289,707 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E1 Start 111,759,776 bp[2] End 111,784,296 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in beta cell frontal pole Brodmann area 10 right frontal lobe middle frontal gyrus paraflocculus of cerebellum Brodmann area 9 stromal cell of endometrium cingulate gyrus cerebellar vermis Top expressed in calvaria left lobe of liver facial motor nucleus lacrimal gland stroma of bone marrow anterior horn of spinal cord endothelial cell of lymphatic vessel somite primitive streak crypt of lieberkuhn of small intestine More reference expression data BioGPS n/a
Gene ontology Molecular function aminoacyl-tRNA ligase activity nucleotide binding amino acid binding metal ion binding ligase activity RNA binding nucleic acid binding ATP binding tRNA binding alanine-tRNA ligase activity aminoacyl-tRNA editing activity Ser-tRNA(Ala) hydrolase activity zinc ion binding translation regulator activity Cellular component membrane mitochondrion extracellular exosome cytoplasm cytosol Biological process negative regulation of neuron apoptotic process tRNA aminoacylation protein biosynthesis neuromuscular process controlling balance tRNA processing tRNA aminoacylation for protein translation tRNA modification neuromuscular process cerebellar Purkinje cell layer development regulation of translational fidelity alanyl-tRNA aminoacylation aminoacyl-tRNA metabolism involved in translational fidelity regulation of cytoplasmic translational fidelity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 16 234734 Ensembl ENSG00000090861 ENSMUSG00000031960 UniProt P49588 Q8BGQ7 RefSeq (mRNA) NM_001605 NM_146217 RefSeq (protein) NP_001596 NP_666329 Location (UCSC) Chr 16: 70.25 – 70.29 Mb Chr 8: 111.76 – 111.78 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth Disease type 2 (CMT2) and other peripheral neuropathies have been linked to mutations in the AARS1, GARS1, HARS1, WARS1, and YARS1 genes.^[6] Mutations in these genes can encode for faulty aminoacyl-tRNA synthetases, which affects a highly conserved amino acid in the helical domain of cytoplasmic AARS1.^[7] This disrupts the ability to charge tRNA with its corresponding amino acids, which leads to impaired protein synthesis. In AARS1, mutations are associated with both autosomal dominant and recessive forms of CMT2.^[8]

Trichothiodystrophy

In addition to its role in CMT2, mutations in the AARS1 gene have also been implicated in non-photosensitive trichothiodystrophy (NPS-TTD),^[9] a rare hereditary neurodevelopmental disorder. Trichothiodystrophy (TTD) is defined by sulfur-deficient brittle hair, nails, and scaly skin,^[9] but presents with variable clinical features. Unlike the photosensitive form of TTD (PS-TTD), which exhibits features of progressive neuropathy and accelerated aging, NPS-TTD is not associated with premature aging.^[9]

Research has identified AARS1, along with methionyl-tRNA synthetase 1 as genes in which variants can contribute to the development NPS-TTD.^[9] These variants lead to the instability of the respective enzymes which they encode, affecting the rate of tRNA charging,^[9] which is the first step in protein translation.