Alanine–tRNA ligase, mitochondrial

AARS2
Identifiers
Aliases	AARS2, AARSL, COXPD8, LKENP, MT-ALARS, MTALARS, alanyl-tRNA synthetase 2, mitochondrial
External IDs	OMIM: 612035; MGI: 2681839; GeneCards: AARS2
Enzyme activity
Gene location (Human)
Chr.	Chromosome 6 (human)
End	44,313,347 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	45,831,769 bp
RNA expression pattern
	Top expressed in
	tendon of biceps brachii; ; pancreatic ductal cell; ; nipple; ; skin of arm; ; cerebellar vermis; ; vena cava; ; mucosa of ileum; ; endothelial cell; ; vulva; ; pylorus;
	Top expressed in
	otolith organ; ; utricle; ; hand; ; seminiferous tubule; ; spermatocyte; ; epiblast; ; foot; ; quadriceps femoris muscle; ; right kidney; ; knee joint;
	More reference expression data
	n/a
Gene ontology
Molecular function	aminoacyl-tRNA ligase activity; nucleotide binding; amino acid binding; tRNA binding; metal ion binding; ligase activity; RNA binding; nucleic acid binding; alanine-tRNA ligase activity; ATP binding; zinc ion binding; aminoacyl-tRNA editing activity;
Cellular component	cytoplasm; mitochondrion;
Biological process	tRNA aminoacylation; protein biosynthesis; alanyl-tRNA aminoacylation; tRNA modification; mitochondrial alanyl-tRNA aminoacylation; mitochondrial respiratory chain complex assembly; aminoacyl-tRNA metabolism involved in translational fidelity;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	57505
	224805
	ENSG00000124608
	ENSMUSG00000023938
	Q5JTZ9
	Q14CH7
	NM_020745
	NM_198608; NM_001358000
	NP_065796
	NP_941010; NP_001344929
	Wikidata
View/Edit Human	View/Edit Mouse

Alanine–tRNA ligase, mitochondrial, also known as alanyl-tRNA synthetase 2 (AARS2), is an enzyme that in humans is encoded by the AARS2 gene. Like the cytosolic variety, AARS2, this enzyme functions as an alanine–tRNA ligase, which means it attaches the amino acid alanine to the corresponding transfer RNA (tRNA^Ala) in preparation of RNA-to-protein translation.

Clinical relevance

Mutations in the AARS2 gene result in infantile mitochondrial cardiomyopathies. Progressive leukoencephalopathy with Ovarian Failure (LKENP).

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000124608 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023938 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: alanyl-tRNA synthetase 2".
↑ Bonnefond L, Fender A, Rudinger-Thirion J, Giegé R, Florentz C, Sissler M (March 2005). "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS". Biochemistry. 44 (12): 4805–16. doi:10.1021/bi047527z. PMID 15779907.
↑ EC 6.1.1.7
↑ Götz A, Tyynismaa H, Euro L, Ellonen P, Hyötyläinen T, Ojala T, Hämäläinen RH, Tommiska J, Raivio T, Oresic M, Karikoski R, Tammela O, Simola KO, Paetau A, Tyni T, Suomalainen A (May 2011). "Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy". American Journal of Human Genetics. 88 (5): 635–42. doi:10.1016/j.ajhg.2011.04.006. PMC 3146718. PMID 21549344.

Nakayama M, Kikuno R, Ohara O (November 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Research. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (October 1999). "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 6 (5): 337–45. doi:10.1093/dnares/6.5.337. PMID 10574462.
Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ (2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE. 5 (9) e12862. Bibcode:2010PLoSO...512862H. doi:10.1371/journal.pone.0012862. PMC 2943476. PMID 20877624.
Bonnefond L, Fender A, Rudinger-Thirion J, Giegé R, Florentz C, Sissler M (March 2005). "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS". Biochemistry. 44 (12): 4805–16. doi:10.1021/bi047527z. PMID 15779907.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
Fan Y, Han J, Yang Y (2022). "Novel mitochondrial alanyl-tRNA synthetase 2 (AARS2) heterozygous mutations in a Chinese patient with adult-onset leukoencephalopathy". BMC Neurology. 22 (1) 214. doi:10.1186/s12883-022-02720-3. PMC 9175470. PMID 35676634.

Lynch DS, Zhang WJ, Lakshmanan R, Kinsella JA, Uzun GA, Karbay M, Tufekcioglu Z, Hanagasi H, Burke G, Foulds N, et al. (2016). "Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia". JAMA Neurology. 73 (12): 1433–1439. doi:10.1001/jamaneurol.2016.2229. PMID 27749956.

Götz A, Tyynismaa H, Euro L, Ellonen P, Hyötyläinen T, Ojala T, Hämäläinen RH, Tommiska J, Raivio T, Oresic M, et al. (2011). "Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy". American Journal of Human Genetics. 88 (5): 635–642. doi:10.1016/j.ajhg.2011.04.006. PMC 3146718. PMID 21549344.

Wang X, Wang Q, Tang H, Chen B, Dong X, Niu S, Li S, Shi Y, Shan W, Zhang Z (2019). "Novel Alanyl-tRNA Synthetase 2 Pathogenic Variants in Leukodystrophies". Frontiers in Neurology. 10 1321. doi:10.3389/fneur.2019.01321. PMC 6928200. PMID 31920941.

Kiraly-Borri C, Jevon G, Ji W, Jeffries L, Ricciardi JL, Konstantino M, Ackerman KG, Lakhani SA (2019). "Siblings with lethal primary pulmonary hypoplasia and compound heterozygous variants in the AARS2 gene: further delineation of the phenotypic spectrum". Cold Spring Harbor Molecular Case Studies. 5 (3) a003699. doi:10.1101/mcs.a003699. PMC 6549552. PMID 30819764.

De Michele G, Galatolo D, Lieto M, Maione L, Cocozza S, Santorelli FM, Filla A (2020). "New AARS2 Mutations in Two Siblings With Tremor, Downbeat Nystagmus, and Primary Amenorrhea: A Benign Phenotype Without Leukoencephalopathy". Movement Disorders Clinical Practice. 7 (6): 684–687. doi:10.1002/mdc3.12958. PMC 7328423. PMID 32626814.

Euro L, Konovalova S, Asin-Cayuela J, Tulinius M, Griffin H, Horvath R, Taylor RW, Chinnery PF, Schara U, Thorburn DR, et al. (2015). "Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation". Frontiers in Genetics. 6: 21. doi:10.3389/fgene.2015.00021. PMC 4319469. PMID 25705216.

Fine AS, Nemeth CL, Kaufman ML, Fatemi A (2019). "Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination". Journal of Neurodevelopmental Disorders. 11 (1) 29. doi:10.1186/s11689-019-9292-y. PMC 6913031. PMID 31839000.

Götz A, Suomalainen A (2012). "Mitochondrial alanyl-tRNA synthetase (AARS2) mutations: adult leukoencephalopathy and infantile cardiomyopathy". Journal of Internal Medicine. 271 (6): 595–597. doi:10.1111/j.1365-2796.2012.02568.x. PMID 22759240.

Dallabona C, Diodato D, Kevelam SH, Haack TB, Wong LJ, Salomons GS, Agosta F, Mariotti C, Smits BW, Rodenburg RJ, et al. (2014). "Novel (ovario) leukodystrophy related to AARS2 mutations". Neurology. 82 (23): 2063–2071. doi:10.1212/WNL.0000000000000415. PMC 4118500. PMID 24808023.

External links

AARS2 human gene location in the UCSC Genome Browser.
AARS2 human gene details in the UCSC Genome Browser.
CureARS non profit organisation supporting families affected by ARS mutations, including AARS2.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000124608 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023938 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: alanyl-tRNA synthetase 2".

[pmid15779907-6] Bonnefond L, Fender A, Rudinger-Thirion J, Giegé R, Florentz C, Sissler M (March 2005). "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS". Biochemistry. 44 (12): 4805–16. doi:10.1021/bi047527z. PMID 15779907.

[7] EC 6.1.1.7

[pmid21549344-8] Götz A, Tyynismaa H, Euro L, Ellonen P, Hyötyläinen T, Ojala T, Hämäläinen RH, Tommiska J, Raivio T, Oresic M, Karikoski R, Tammela O, Simola KO, Paetau A, Tyni T, Suomalainen A (May 2011). "Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy". American Journal of Human Genetics. 88 (5): 635–42. doi:10.1016/j.ajhg.2011.04.006. PMC 3146718. PMID 21549344.

v t e Enzymes: CO CS and CN ligases (EC 6.1-6.3)
6.1: Carbon-Oxygen	Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-Alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine
6.2: Carbon-Sulfur	(2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA synthase 2-furoate—CoA ligase 3-alpha,7-alpha-dihydroxy-5-beta-cholestanate—CoA ligase 3-hydroxybenzoate—CoA ligase 3-hydroxypropionyl-CoA synthase 4-chlorobenzoate—CoA ligase 4-Coumarate-CoA ligase 4-hydroxybenzoate—CoA ligase 6-carboxyhexanoate—CoA ligase Acetate—ACP ligase Acetate—CoA ligase (ADP-forming) Acetoacetate—CoA ligase Acetyl—CoA synthetase Acid—CoA ligase (GDP-forming) Anthranilate—CoA ligase Arachidonate—CoA ligase Benzoate—CoA ligase Biotin—CoA ligase (butirosin acyl-carrier protein)—L-glutamate ligase Butyrate—CoA ligase Cholate—CoA ligase Citrate—CoA ligase (citrate (pro-3S)-lyase) ligase Dicarboxylate—CoA ligase Glutarate—CoA ligase Long-chain-fatty-acid—ACP ligase Long-chain-fatty-acid—CoA ligase Malate—CoA ligase Malonate—CoA ligase o-Succinylbenzoate—CoA ligase Oxalate—CoA ligase Phenylacetate—CoA ligase Phytanate—CoA ligase Propionate—CoA ligase Succinate—CoA ligase (ADP-forming) Succinate—CoA ligase (GDP-forming) Succinyl—CoA synthetase trans-Feruloyl—CoA synthase
6.3: Carbon-Nitrogen	Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Alanine–tRNA ligase, mitochondrial

Clinical relevance

References

Further reading

See also

External links