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HARS2 histidyl-tRNA synthetase 2, mitochondrial [ Homo sapiens (human) ]

Gene ID: 23438, updated on 3-Nov-2024

Summary

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Official Symbol
HARS2provided by HGNC
Official Full Name
histidyl-tRNA synthetase 2, mitochondrialprovided by HGNC
Primary source
HGNC:HGNC:4817
See related
Ensembl:ENSG00000112855 MIM:600783; AllianceGenome:HGNC:4817
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HO3; HARSL; HARSR; HisRS; PRLTS2
Summary
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]
Expression
Ubiquitous expression in colon (RPKM 9.6), endometrium (RPKM 9.1) and 25 other tissues See more
Orthologs
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Genomic context

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See HARS2 in Genome Data Viewer
Location:
5q31.3
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (140691455..140699305)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (141216842..141224701)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (140071040..140078890)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:140052035-140052830 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:140052831-140053626 Neighboring gene WD repeat domain 55 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23284 Neighboring gene DND microRNA-mediated repression inhibitor 1 Neighboring gene histidyl-tRNA synthetase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23285 Neighboring gene HARS1 and HARS2 bidirectional promoter region Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23288 Neighboring gene NANOG hESC enhancer GRCh37_chr5:140082322-140082864 Neighboring gene zinc finger matrin-type 2 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:140090124-140091323 Neighboring gene uncharacterized LOC105378198 Neighboring gene vault RNA 1-1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome. Karstensen HG, et al. Eur J Med Genet, 2020 Mar. PMID 31449985
  2. Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation. Gong S, et al. J Biol Chem, 2020 Jan 24. PMID 31819004, Free PMC Article
  3. A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families. Demain LAM, et al. J Hum Genet, 2020 Mar. PMID 31827252, Free PMC Article
  4. Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss. Yu J, et al. Hereditas, 2020 Nov 24. PMID 33228777, Free PMC Article
  5. [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes]. Lei YB, et al. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2023 Dec 7. PMID 38186093

See all (64) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].
    Title: [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].
  2. Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss.
    Title: Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss.
  3. Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome.
    Title: Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome.
  4. A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.
    Title: A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.
  5. Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation.
    Title: Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation.
  6. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome.
    Title: Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome.
  7. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  8. This protein has been found differentially expressed in the anterior cingulate cortex in men patients with schizophrenia.
    Title: Sex-specific proteome differences in the anterior cingulate cortex of schizophrenia.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Perrault syndrome 2
MedGen: C3554105 OMIM: 614926 GeneReviews: Perrault Syndrome
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
matrix gag HIV-1 MA is identified to have a physical interaction with histidyl-tRNA synthetase 2, mitochondrial (HARS2; HO3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
gag HO3 binds to the HIV-1 Matrix protein (amino acids 26 and 27) resulting in the incorporation of HO3 into virus particles and the enhancement of virus infectivity PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA binding HDA PubMed 
enables RNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables histidine-tRNA ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables histidine-tRNA ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables histidine-tRNA ligase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables histidine-tRNA ligase activity TAS
Traceable Author Statement
more info
  
enables identical protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in histidyl-tRNA aminoacylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in histidyl-tRNA aminoacylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tRNA aminoacylation for protein translation TAS
Traceable Author Statement
more info
  
involved_in translation NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
histidine--tRNA ligase, mitochondrial
Names
HARS-related
histidine tRNA ligase 2, mitochondrial (putative)
histidine translase
histidine-tRNA ligase homolog
histidyl-tRNA synthetase 2, mitochondrial (putative)
histidyl-tRNA synthetase 2, mitochondrial, hisRS
probable histidine--tRNA ligase, mitochondrial
probable histidyl-tRNA synthetase, mitochondrial
NP_001265660.1
NP_001265661.1
NP_001350464.1
NP_001350465.1
NP_036340.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_021415.1 RefSeqGene

    Range
    5023..12873
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1376

mRNA and Protein(s)

  1. NM_001278731.2 → NP_001265660.1  histidine--tRNA ligase, mitochondrial isoform 2 precursor

    See identical proteins and their annotated locations for NP_001265660.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which lacks an internal segment and is shorter than isoform 1.
    Source sequence(s)
    AK293390, BC014982, DA150729
    Consensus CDS
    CCDS64267.1
    UniProtKB/TrEMBL
    B2R7G6
    Related
    ENSP00000423616.1, ENST00000508522.5
    Conserved Domains (1) summary
    PLN02972
    Location:36 → 479
    PLN02972; Histidyl-tRNA synthetase

  2. NM_001278732.2 → NP_001265661.1  histidine--tRNA ligase, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site and lacks two alternate in-frame exons in the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1. This isoform (3) lacks the transit peptide present in isoforms 1 and 2, hence it is not likely to localize to the mitochondrion.
    Source sequence(s)
    AK293269, BC014982, BQ228600, DA150729
    UniProtKB/TrEMBL
    B4DDN8
    Conserved Domains (2) summary
    cd00773
    Location:32 → 251
    HisRS-like_core; Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain. HisRS is a homodimer. It is responsible for the attachment of histidine to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent ...
    cd00859
    Location:265 → 356
    HisRS_anticodon; HisRS Histidyl-anticodon binding domain. HisRS belongs to class II aminoacyl-tRNA synthetases (aaRS). This alignment contains the anticodon binding domain, which is responsible for specificity in tRNA-binding, so that the activated amino acid is ...

  3. NM_001363535.2 → NP_001350464.1  histidine--tRNA ligase, mitochondrial isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (4).
    Source sequence(s)
    AC116353
    Consensus CDS
    CCDS87329.1
    UniProtKB/TrEMBL
    A0A2R8Y5P7, B2R7G6
    Related
    ENSP00000494965.1, ENST00000646468.1
    Conserved Domains (1) summary
    cl28413
    Location:12 → 510
    HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  4. NM_001363536.2 → NP_001350465.1  histidine--tRNA ligase, mitochondrial isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (5) is shorter at the N-terminus compared to isoform 4.
    Source sequence(s)
    AC116353
    Consensus CDS
    CCDS87330.1
    UniProtKB/TrEMBL
    A0A2R8Y6I1, B2R7G6
    Related
    ENSP00000496011.1, ENST00000642970.1
    Conserved Domains (1) summary
    cl28413
    Location:1 → 434
    HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

  5. NM_012208.4 → NP_036340.1  histidine--tRNA ligase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_036340.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC014982, DA150729
    Consensus CDS
    CCDS4238.1
    UniProtKB/Swiss-Prot
    B4DDY8, P49590
    UniProtKB/TrEMBL
    B2R7G6
    Related
    ENSP00000230771.3, ENST00000230771.9
    Conserved Domains (1) summary
    cl28413
    Location:12 → 504
    HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    140691455..140699305
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    141216842..141224701
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49590.1 GenPept UniProtKB/Swiss-Prot:P49590

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