Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438). (updated: July 18, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 55%
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The reference OMIM entry for this protein is 601065
Alanyl-trna synthetase; aars
Alars
DESCRIPTION
The AARS gene encodes alanyl-tRNA synthetase. Each of the amino acid synthetases catalyzes the attachment of their respective amino acids to the appropriate tRNA. The class II Escherichia coli and human alanyl-tRNA synthetases cross-acylate their respective tRNAs and require, for aminoacylation, an acceptor helix G3:U70 basepair that is conserved in evolution (Shiba et al., 1995). Some of the amino acid synthetases are targets for autoantibodies in the autoimmune disease polymyositis/dermatomyositis (Nichols et al., 1995) including histidyl-RS (
142810), threonyl-RS (
187790), isoleucyl-RS (
600709), glycyl-RS (
600287) and alanyl-RS.
CLONING
Shiba et al. (1995) reported the primary structure and expression of an active human alanyl-tRNA synthetase. The N-terminal 498 amino acids of the 968-residue polypeptide showed 41% identity with the E. coli protein. The human protein contains the class-defining domain of the E. coli enzyme, which includes the part needed for recognition of the acceptor helix G3:U70 basepair as an RNA signal for alanine. The authors concluded that mutagenesis, modeling, domain organization, and biochemical characterization of the E. coli protein are valid as a template for the human protein. Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 2 catalytic-null splice variants for AlaRS.
MAPPING
Nichols et al. (1995) mapped the alanyl-RS gene by fluorescence in situ hybridization to chromosome 16q22. By radiation hybrid panel analysis, Maas et al. (2001) mapped the AARS gene centromeric to the KARS gene (
601421) and the ADAT1 gene (
604230) in region 16q22.2-q22.3.
GENE FUNCTION
The folding of mRNA influences a diverse range of biologic events such as mRNA splicing and processing, and translational control and regulation. Because the structure of mRNA is determined by its nucleotide sequence and its environment, Shen et al. (1999) examined whether the folding of mRNA could be influenced by the presence of single-nucleotide polymorphisms (SNPs). They reported marked differences in mRNA secondary structure associated with SNPs in the coding region of 2 human mRNAs: alanyl-tRNA synthetase and replication protein A, 70-kD subunit (RPA70;
179835). Enzymatic probing of SNP-containing fragments of the mRNAs revealed pronounced allelic differences in cleavage pattern at sites 14 or 18 nucleotides away from the SNP, suggesting that a single-nucleotide variation can give rise to different mRNA folds. By using oligodeoxyribonucleotides complementary to the region of different allelic structures in the RPA70 mRNA, but not extending to the SNP itself, they found that the SNP exerted an allele ...
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Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601065 was added.