Protein Variants | Comment | Organism |
---|---|---|
A77V | naturally occuring mutation of a catalytic residue. the mutant likely affects alanine binding resulting in either totally inactive enzyme or with little aminoacylation activity due to decreased affinity to alanine | Homo sapiens |
E405K | naturally occuring mutation of a structural residue within the tRNA recognition subdomain of the aminoacylation domain, the mutation leads to a partly reduced rate of tRNA aminoacylation due to structural instability in the tRNA recognition fold | Homo sapiens |
F50C | naturally occuring mutation, leads to reduced rate of aminoacylation due to instability of alanine- and ATP-binding sites and impaired alanyl-adenylate formation | Homo sapiens |
G965R | naturally occuring mutation predicted to impair protein folding and stability resulting in loss of aminoacylation activity | Homo sapiens |
additional information | patient haplotypes around the AARS2 mutation, some patients show heterozygous mutations R592W/L155R, R592W/R329H, R592W/A961V, R592W/C218L, or R592W/Y539C, but the same pehnotype as homozygous R592W mutants. Mapping and function predictions of AARS2 mutations associated with cardiomyopathy and leukodystrophy | Homo sapiens |
R199C | naturally occuring mutation of a catalytic residue involved in ATP binding, the mutantion leads to reduced rate of tRNA aminoacylation due to affected ATP-binding and impaired alanyl-adenylate formation | Homo sapiens |
R592W | a naturally occuring lethal mutation in the editing domain of AARS2 causing a cardiomyopathy phenotype, homology modeling of the AARS2 missense mutant, overview. The AARS2 cardiomyopathy mutation R592W is a common founder mutation and carried by all the identified patients with the severe infantile-onset phenotype | Homo sapiens |
R592W/A961V | naturally occuring lethal mutation R592W in gene AARS2 causing infantile cardiomyopathy, mutation A961V is predicted to impair protein folding and stability resulting in loss of aminoacylation activity | Homo sapiens |
R592W/C218L | naturally occuring lethal mutation R592W in gene AARS2 causing infantile cardiomyopathy, truncated mutant | Homo sapiens |
R592W/L155R | naturally occuring lethal mutation R592W in gene AARS2 causing infantile cardiomyopathy, mutation L155R is predicted to impair protein folding and stability resulting in loss of aminoacylation activity | Homo sapiens |
R592W/R329H | naturally occuring lethal mutation R592W in gene AARS2 causing infantile cardiomyopathy, mutation R329H is predicted to impair protein folding and stability resulting in loss of aminoacylation activity | Homo sapiens |
R592W/Y539C | naturally occuring lethal mutation R592W in gene AARS2 causing infantile cardiomyopathy. The Y539C mutation causes a dramatic decrease of aminoacylation rate due to impaired tRNA binding and positioning of the 3'-end within the active site | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Homo sapiens | 5739 | - |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q5JTZ9 | - |
- |
Synonyms | Comment | Organism |
---|---|---|
AARS2 | - |
Homo sapiens |
mitochondrial alanyl-tRNA synthetase | - |
Homo sapiens |
mtAlaRS | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is recognized as a disease gene for mitochondrial disease. Mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) is observed both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. The cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. All mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. The cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. Molecular basis of the distinct tissue-specific phenotypic outcomes of enzyme mutantions, structure analysis and homology modeling, overview | Homo sapiens |
additional information | enzyme structure modeling, analysis of the contact surface between linker safety belt, and beta-barrel of the editing domain in modeled human mitochondrial AlaRS, overview | Homo sapiens |
physiological function | the accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The mitochondrial alanyl-tRNA synthetase (mtAlaRS) differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged within correct amino acids | Homo sapiens |