NARS2

Protein identityUniProt · HPA

UniProt accession

Q96I59

Gene

NARS2

Ensembl

ENSG00000137513

Chromosome

11

Canonical length

477 aa

Protein class

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

Subcellular location

Nucleoplasm,Mitochondria,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]

Canonical amino-acid sequenceUniProt

477 residues, UniProt reviewed canonical sequence.

>Q96I59|NARS2
     1  MLGVRCLLRS VRFCSSAPFP KHKPSAKLSV RDALGAQNAS GERIKIQGWI RSVRSQKEVL
    61  FLHVNDGSSL ESLQVVADSG LDSRELNFGS SVEVQGQLIK SPSKRQNVEL KAEKIKVIGN
   121  CDAKDFPIKY KERHPLEYLR QYPHFRCRTN VLGSILRIRS EATAAIHSFF KDSGFVHIHT
   181  PIITSNDSEG AGELFQLEPS GKLKVPEENF FNVPAFLTVS GQLHLEVMSG AFTQVFTFGP
   241  TFRAENSQSR RHLAEFYMIE AEISFVDSLQ DLMQVIEELF KATTMMVLSK CPEDVELCHK
   301  FIAPGQKDRL EHMLKNNFLI ISYTEAVEIL KQASQNFTFT PEWGADLRTE HEKYLVKHCG
   361  NIPVFVINYP LTLKPFYMRD NEDGPQHTVA AVDLLVPGVG ELFGGGLREE RYHFLEERLA
   421  RSGLTEVYQW YLDLRRFGSV PHGGFGMGFE RYLQCILGVD NIKDVIPFPR FPHSCLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NARS2 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)

0.28

Highest tissue expression

23 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NARS2.

Disease | AllUniProt

Conditions NARS2 is implicated in, by any mechanism.

• Combined oxidative phosphorylation deficiency 24 (COXPD24) MIM:616239
• Deafness, autosomal recessive, 94 (DFNB94) MIM:618434

Disease | GeneticClinVar

34 pathogenic / likely-pathogenic of 424 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined oxidative phosphorylation defect type 24
• Hearing loss, autosomal recessive 94
• Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1
• NARS2-related disorder
• Mitochondrial disease

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)

0.86

gnomAD pLI

0

gnomAD missense Z

-0.76

DepMap mean gene effect

-0.24

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

• asparaginyl-tRNA aminoacylation

Molecular functions

• asparagine-tRNA ligase activity
• ATP binding
• nucleic acid binding

Cellular components

• cytosol
• mitochondrial matrix
• mitochondrion
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Aspartyl/Asparaginyl-tRNA synthetase, class IIb
• Aminoacyl-tRNA synthetase, class II (D/K/N)
• OB-fold nucleic acid binding domain, AA-tRNA synthetase-type
• Asparagine-tRNA ligase
• Aminoacyl-tRNA synthetase, class II
• Nucleic acid-binding, OB-fold
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• tRNA synthetases class II (D, K and N)
• OB-fold nucleic acid binding domain

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Deafness
• Leigh syndrome
• Ligase
• Mitochondrion
• Non-syndromic deafness
• Nucleotide-binding
• Primary mitochondrial disease
• Protein biosynthesis
• Transit peptide