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Details on Person UniProt:Q5JTZ9 AARS2

Class:IdReferenceGeneProduct:250002
_chainChangeLogtransit peptide:1-23 added on Fri February 6 2015;chain:24-985 added on Fri February 6 2015
_displayNameUniProt:Q5JTZ9 AARS2
_timestamp2025-02-21 20:15:05
chaintransit peptide:1-23
chain:24-985
checksum721368BD05474F86
commentFUNCTION 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). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:21549344). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as CGAS (PubMed:39322678). Acts as an inhibitor of cGAS/STING signaling by catalyzing lactylation of CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (PubMed:39322678).CATALYTIC ACTIVITY tRNA(Ala) + L-alanine + ATP = L-alanyl-tRNA(Ala) + AMP + diphosphateCATALYTIC ACTIVITY (S)-lactate + ATP + H(+) = (S)-lactoyl-AMP + diphosphateCATALYTIC ACTIVITY (S)-lactoyl-AMP + L-lysyl-[protein] = N(6)-[(S)-lactoyl]-L-lysyl-[protein] + AMP + 2 H(+)COFACTOR Binds 1 zinc ion per subunit.SUBUNIT Monomer.INTERACTION Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the class-II aminoacyl-tRNA synthetase family.CAUTION Given that AARS2 is a mitochondrial protein, it is unclear how it can mediate lactylation of CGAS, which localizes in the cytosol and nucleus.SEQUENCE CAUTION Extended N-terminus.
created[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
descriptionrecommendedName: fullName evidence="2"Alanine--tRNA ligase, mitochondrial ecNumber evidence="2"6.1.1.7 alternativeName: fullName evidence="2"Alanyl-tRNA synthetase shortName evidence="2"AlaRS alternativeName: fullName evidence="9"Protein lactyltransferase AARS2 ecNumber evidence="8"6.-.-.-
geneNameAARS2
AARSL
KIAA1270
identifierQ5JTZ9
isSequenceChangedFALSE
keyword3D-structure
Aminoacyl-tRNA synthetase
ATP-binding
Cardiomyopathy
Disease variant
Ligase
Metal-binding
Mitochondrion
Neurodegeneration
Nucleotide-binding
Premature ovarian failure
Primary mitochondrial disease
Protein biosynthesis
Proteomics identification
Reference proteome
RNA-binding
Transit peptide
tRNA-binding
Zinc
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameAARS2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8990434] ENSEMBL:ENSG00000124608 AARS2 [Homo sapiens]
secondaryIdentifierSYAM_HUMAN
A2RRN5
Q8N198
Q96D02
Q9ULF0
sequenceLength985
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:379653] AARS2 [mitochondrial matrix] [Homo sapiens]
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