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

Summary

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: mouse all
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Genomic context

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_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[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].
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.
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.
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.
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
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.

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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	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S2381 (e-PCR)
- UniSTS:23051

G20504 (e-PCR)
- UniSTS:40551

A005U15 (e-PCR)
- UniSTS:40552

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	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 more info	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

EC 6.1.1.21

NP_001265661.1

EC 6.1.1.21

NP_001350464.1

EC 6.1.1.21

NP_001350465.1

EC 6.1.1.21

NP_036340.1

EC 6.1.1.21

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

NG_021415.1 RefSeqGene

Range

5023..12873

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1376

mRNA and Protein(s)

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
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 ...
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]
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]
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]