HARS2

Protein identityUniProt · HPA

UniProt accession

P49590

Gene

HARS2

Ensembl

ENSG00000112855

Chromosome

5

Canonical length

506 aa

Protein class

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

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is an enzyme belonging to the class II family of aminoacyl-tRNA synthetases. Functioning in the synthesis of histidyl-transfer RNA, the enzyme plays an accessory role in the regulation of protein biosynthesis. The gene is located in a head-to-head orientation with HARS on chromosome five, where the homologous genes likely share a bidirectional promoter. Mutations in this gene are associated with the pathogenesis of Perrault syndrome, which involves ovarian dysgenesis and sensorineural hearing loss. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

Canonical amino-acid sequenceUniProt

506 residues, UniProt reviewed canonical sequence.

>P49590|HARS2
     1  MPLLGLLPRR AWASLLSQLL RPPCASCTGA VRCQSQVAEA VLTSQLKAHQ EKPNFIIKTP
    61  KGTRDLSPQH MVVREKILDL VISCFKRHGA KGMDTPAFEL KETLTEKYGE DSGLMYDLKD
   121  QGGELLSLRY DLTVPFARYL AMNKVKKMKR YHVGKVWRRE SPTIVQGRYR EFCQCDFDIA
   181  GQFDPMIPDA ECLKIMCEIL SGLQLGDFLI KVNDRRIVDG MFAVCGVPES KFRAICSSID
   241  KLDKMAWKDV RHEMVVKKGL APEVADRIGD YVQCHGGVSL VEQMFQDPRL SQNKQALEGL
   301  GDLKLLFEYL TLFGIADKIS FDLSLARGLD YYTGVIYEAV LLQTPTQAGE EPLNVGSVAA
   361  GGRYDGLVGM FDPKGHKVPC VGLSIGVERI FYIVEQRMKT KGEKVRTTET QVFVATPQKN
   421  FLQERLKLIA ELWDSGIKAE MLYKNNPKLL TQLHYCESTG IPLVVIIGEQ ELKEGVIKIR
   481  SVASREEVAI KRENFVAEIQ KRLSES

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HARS2 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)

0.3

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HARS2.

Disease | AllUniProt

Conditions HARS2 is implicated in, by any mechanism.

• Perrault syndrome 2 (PRLTS2) MIM:614926

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 295 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Perrault syndrome 2
• Perrault syndrome
• Sensorineural hearing loss disorder
• Gastric cancer

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)

0.74

gnomAD pLI

0

gnomAD missense Z

0.04

DepMap mean gene effect

-0.31

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

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

Molecular functions

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

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Anticodon-binding
• Histidine-tRNA ligase/ATP phosphoribosyltransferase regulatory subunit
• Aminoacyl-tRNA synthetase, class II
• Histidine-tRNA ligase
• Histidyl-anticodon-binding
• Anticodon-binding domain superfamily
• Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Anticodon binding domain
• Histidyl-tRNA synthetase

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Deafness
• Ligase
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of HARS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HSPD1
• MTG2
• RPUSD4