AARS2

Protein identityUniProt · HPA

UniProt accession

Q5JTZ9

Gene

AARS2

Ensembl

ENSG00000124608

Chromosome

6

Canonical length

985 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. Aminoacyl-tRNA synthetases play critical roles in mRNA translation by charging tRNAs with their cognate amino acids. The encoded protein is a mitochondrial enzyme that specifically aminoacylates alanyl-tRNA. Mutations in this gene are a cause of combined oxidative phosphorylation deficiency 8. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

985 residues, UniProt reviewed canonical sequence.

>Q5JTZ9|AARS2
     1  MAASVAAAAR RLRRAIRRSP AWRGLSHRPL SSEPPAAKAS AVRAAFLNFF RDRHGHRLVP
    61  SASVRPRGDP SLLFVNAGMN QFKPIFLGTV DPRSEMAGFR RVANSQKCVR AGGHHNDLED
   121  VGRDLSHHTF FEMLGNWAFG GEYFKEEACN MAWELLTQVY GIPEERLWIS YFDGDPKAGL
   181  DPDLETRDIW LSLGVPASRV LSFGPQENFW EMGDTGPCGP CTEIHYDLAG GVGAPQLVEL
   241  WNLVFMQHNR EADGSLQPLP QRHVDTGMGL ERLVAVLQGK HSTYDTDLFS PLLNAIQQGC
   301  RAPPYLGRVG VADEGRTDTA YRVVADHIRT LSVCISDGIF PGMSGPPLVL RRILRRAVRF
   361  SMEILKAPPG FLGSLVPVVV ETLGDAYPEL QRNSAQIANL VSEDEAAFLA SLERGRRIID
   421  RTLRTLGPSD MFPAEVAWSL SLCGDLGLPL DMVELMLEEK GVQLDSAGLE RLAQEEAQHR
   481  ARQAEPVQKQ GLWLDVHALG ELQRQGVPPT DDSPKYNYSL RPSGSYEFGT CEAQVLQLYT
   541  EDGTAVASVG KGQRCGLLLD RTNFYAEQGG QASDRGYLVR AGQEDVLFPV ARAQVCGGFI
   601  LHEAVAPECL RLGDQVQLHV DEAWRLGCMA KHTATHLLNW ALRQTLGPGT EQQGSHLNPE
   661  QLRLDVTTQT PLTPEQLRAV ENTVQEAVGQ DEAVYMEEVP LALTAQVPGL RSLDEVYPDP
   721  VRVVSVGVPV AHALDPASQA ALQTSVELCC GTHLLRTGAV GDLVIIGDRQ LSKGTTRLLA
   781  VTGEQAQQAR ELGQSLAQEV KAATERLSLG SRDVAEALRL SKDIGRLIEA VETAVMPQWQ
   841  RRELLATVKM LQRRANTAIR KLQMGQAAKK TQELLERHSK GPLIVDTVSA ESLSVLVKVV
   901  RQLCEQAPST SVLLLSPQPM GKVLCACQVA QGAMPTFTAE AWALAVCSHM GGKAWGSRVV
   961  AQGTGSTTDL EAALSIAQTY ALSQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AARS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

9.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AARS2.

Disease | AllUniProt

Conditions AARS2 is implicated in, by any mechanism.

• Combined oxidative phosphorylation deficiency 8 (COXPD8) MIM:614096
• Leukoencephalopathy, progressive, with ovarian failure (LKENP) MIM:615889

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 719 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined oxidative phosphorylation defect type 8
• Leukoencephalopathy, progressive, with ovarian failure
• AARS2-related disorder
• Inborn genetic diseases
• Cardiovascular phenotype

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.84

gnomAD pLI

0

gnomAD missense Z

0.07

DepMap mean gene effect

-0.46

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of cGAS/STING signaling pathway
• mitochondrial alanyl-tRNA aminoacylation

Molecular functions

• alanine-tRNA ligase activity
• aminoacyl-tRNA deacylase activity
• ATP binding
• peptide lactyltransferase (ATP-dependent) activity
• tRNA binding
• zinc ion binding

Cellular components

• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Alanine-tRNA ligase, class IIc
• Translation protein, beta-barrel domain superfamily
• Threonyl/alanyl tRNA synthetase, SAD
• Alanine-tRNA ligase, class IIc, anti-codon-binding domain superfamily
• Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily
• Alanyl-tRNA synthetase, class IIc, N-terminal
• Alanyl-tRNA synthetase, class IIc, core domain
• Alanine-tRNA ligase, eukaryota/bacteria
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Alanine--tRNA ligase
• tRNA synthetases class II (A)
• Threonyl and Alanyl tRNA synthetase second additional domain

KeywordsUniProt

• Aminoacyl-tRNA synthetase
• ATP-binding
• Cardiomyopathy
• Ligase
• Metal-binding
• Mitochondrion
• Neurodegeneration
• Nucleotide-binding
• Premature ovarian failure
• Primary mitochondrial disease
• Protein biosynthesis
• RNA-binding
• Transit peptide
• tRNA-binding
• Zinc

InteractionsUniProt · HPA

Protein binding partners of AARS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• QRSL1
• YARS2