RARS2

Protein identityUniProt · HPA

UniProt accession

Q5T160

Gene

RARS2

Ensembl

ENSG00000146282

Chromosome

6

Canonical length

578 aa

Protein class

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

Subcellular location

Mitochondria

OverviewNCBI Gene

This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

578 residues, UniProt reviewed canonical sequence.

>Q5T160|RARS2
     1  MACGFRRAIA CQLSRVLNLP PENLITSISA VPISQKEEVA DFQLSVDSLL EKDNDHSRPD
    61  IQVQAKRLAE KLRCDTVVSE ISTGQRTVNF KINRELLTKT VLQQVIEDGS KYGLKSELFS
   121  GLPQKKIVVE FSSPNVAKKF HVGHLRSTII GNFIANLKEA LGHQVIRINY LGDWGMQFGL
   181  LGTGFQLFGY EEKLQSNPLQ HLFEVYVQVN KEAADDKSVA KAAQEFFQRL ELGDVQALSL
   241  WQKFRDLSIE EYIRVYKRLG VYFDEYSGES FYREKSQEVL KLLESKGLLL KTIKGTAVVD
   301  LSGNGDPSSI CTVMRSDGTS LYATRDLAAA IDRMDKYNFD TMIYVTDKGQ KKHFQQVFQM
   361  LKIMGYDWAE RCQHVPFGVV QGMKTRRGDV TFLEDVLNEI QLRMLQNMAS IKTTKELKNP
   421  QETAERVGLA ALIIQDFKGL LLSDYKFSWD RVFQSRGDTG VFLQYTHARL HSLEETFGCG
   481  YLNDFNTACL QEPQSVSILQ HLLRFDEVLY KSSQDFQPRH IVSYLLTLSH LAAVAHKTLQ
   541  IKDSPPEVAG ARLHLFKAVR SVLANGMKLL GITPVCRM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RARS2 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

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RARS2.

Disease | AllUniProt

Conditions RARS2 is implicated in, by any mechanism.

• Pontocerebellar hypoplasia 6 (PCH6) MIM:611523

Disease | GeneticClinVar

241 pathogenic / likely-pathogenic of 1,075 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pontocerebellar hypoplasia type 6
• Pontoneocerebellar hypoplasia
• Inborn genetic diseases
• RARS2-related disorder
• Lennox-Gastaut syndrome

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)

0.92

gnomAD pLI

0

gnomAD missense Z

-0.06

DepMap mean gene effect

-0.49

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• arginyl-tRNA aminoacylation
• mitochondrial translation
• tRNA aminoacylation for protein translation

Molecular functions

• arginine-tRNA ligase activity
• ATP binding
• RNA binding

Cellular components

• mitochondrial matrix
• mitochondrial membrane
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Arginine-tRNA ligase
• Aminoacyl-tRNA synthetase, class I, conserved site
• DALR anticodon binding
• Aminoacyl-tRNA synthetase, class Ia, anticodon-binding
• Rossmann-like alpha/beta/alpha sandwich fold
• Arginyl-tRNA synthetase, catalytic core domain
• Arginyl tRNA synthetase N-terminal domain superfamily
• tRNA synthetases class I (R), catalytic domain
• DALR anticodon binding domain

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Ligase
• Membrane
• Mitochondrion
• Neurodegeneration
• Nucleotide-binding
• Pontocerebellar hypoplasia
• Protein biosynthesis
• Transit peptide