HARS1 histidyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HARS1provided by HGNC
Official Full Name: histidyl-tRNA synthetase 1provided by HGNC
Primary source: HGNC:HGNC:4816
See related: Ensembl:ENSG00000170445 MIM:142810; AllianceGenome:HGNC:4816
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: HRS; HARS; CMT2W; USH3B
Summary: Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Expression: Ubiquitous expression in brain (RPKM 24.1), skin (RPKM 18.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q31.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (140673905..140691370, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (141199302..141216757, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (140053490..140070955, complement)

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
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?

Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses.
Title: Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses.
Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome.
Title: Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome.
Serological risk factors for concomitant interstitial lung disease in patients with idiopathic inflammatory myopathy.
Title: Serological risk factors for concomitant interstitial lung disease in patients with idiopathic inflammatory myopathy.
the first biochemical analysis of Charcot-Marie-Tooth-associated HARS mutations and underscores how loss of the primary aminoacylation function can contribute to disease pathology.
Title: Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy.
This study suggests that the human HisRS genes, while descending from a common ancestor with dual function for both types of tRNA(His), have acquired highly specialized tRNA recognition properties through evolution.
Title: Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase.
Despite the similar kinetics, differential scanning fluorimetry revealed that Y454S is less thermally stable than Wild Type HARS, and cells from Y454S patients grown at elevated temperatures demonstrate diminished levels of protein synthesis compared to those of Wild Type cells. The thermal sensitivity associated with the Y454S mutation represents a biochemical basis for understanding Usher Syndrome Type IIIB.
Title: The Usher Syndrome Type IIIB Histidyl-tRNA Synthetase Mutation Confers Temperature Sensitivity.
Loss of function mutations in histidyl-tRNA synthetase cause a spectrum of inherited peripheral neuropathies
Title: Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies.
Data suggest that by comparing human and trypanosomatid histidyl-tRNA synthetases (HisRS) may provide opportunities for developing specific inhibitors of Trypanosoma brucei HisRS.
Title: Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases.
Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis.
Title: Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis.
Data indicate that higher anti-Jo1 levels were associated with disease severity in antisynthetase syndrome (ASS) patients.
Title: Functional outcome and prognostic factors in anti-Jo1 patients with antisynthetase syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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
Autosomal dominant Charcot-Marie-Tooth disease type 2W MedGen: C5567486 OMIM: 616625 GeneReviews: Not available	Compare labs
Usher syndrome type 3B MedGen: C3281066 OMIM: 614504 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S1658E (e-PCR)
- UniSTS:151047

WI-19187 (e-PCR)
- UniSTS:32540

D5S1691E (e-PCR)
- UniSTS:151079

D8S2278 (e-PCR)
- UniSTS:473906

PMC156606P4 (e-PCR)
- UniSTS:271411

D8S2279 (e-PCR)
- UniSTS:473907

RH67434 (e-PCR)
- UniSTS:90173

SHGC-17214 (e-PCR)
- UniSTS:13455

D11S3114 (e-PCR)
- UniSTS:152207

PMC55343P6 (e-PCR)
- UniSTS:273329

Hars (e-PCR), detects polymorphism
- UniSTS:143316

RH70258 (e-PCR)
- UniSTS:72933

D5S2775 (e-PCR)
- UniSTS:473843

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay 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 homodimerization activity	IDA Inferred from Direct Assay 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 mitochondrial translation	IBA Inferred from Biological aspect of Ancestor more info
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
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: histidine--tRNA ligase, cytoplasmic

Names: HisRS; Jo-1 antigen; histidine translase

NP_001244969.1

EC 6.1.1.21

NP_001244970.1

EC 6.1.1.21

NP_001244971.1

EC 6.1.1.21

NP_001276021.1

EC 6.1.1.21

NP_001276022.1

EC 6.1.1.21

NP_001276023.1

EC 6.1.1.21

NP_002100.2

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_032158.1 RefSeqGene

Range

5017..22482

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1374

mRNA and Protein(s)

NM_001258040.3 → NP_001244969.1 histidine--tRNA ligase, cytoplasmic isoform 2

See identical proteins and their annotated locations for NP_001244969.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK225776, AK302295, DC394573

Consensus CDS

CCDS58976.1

UniProtKB/TrEMBL

A0A6Q8PF07

Related

ENSP00000411511.2, ENST00000438307.6

Conserved Domains (2) summary

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...

cl28413
Location:56 → 461

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
NM_001258041.3 → NP_001244970.1 histidine--tRNA ligase, cytoplasmic isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK225776

Consensus CDS

CCDS58978.1

UniProtKB/TrEMBL

E7ETE2

Related

ENSP00000387893.2, ENST00000457527.6

Conserved Domains (4) summary

COG0124
Location:56 → 481

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

cd00773
Location:69 → 374

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:388 → 479

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 ...

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...
NM_001258042.3 → NP_001244971.1 histidine--tRNA ligase, cytoplasmic isoform 4

See identical proteins and their annotated locations for NP_001244971.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon and uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC116353, AK225776, AK295219

Consensus CDS

CCDS58977.1

UniProtKB/TrEMBL

A0A6Q8PF07

Related

ENSP00000304668.3, ENST00000307633.7

Conserved Domains (2) summary

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...

cl28413
Location:56 → 441

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
NM_001289092.2 → NP_001276021.1 histidine--tRNA ligase, cytoplasmic isoform 5

See identical proteins and their annotated locations for NP_001276021.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks two alternate in-frame exons in the 5' coding region, compared to variant 1. The encoded protein (isoform 5) is shorter, compared to isoform 1.

Source sequence(s)

AK225776, AK293154, DC394573

Consensus CDS

CCDS75324.1

UniProtKB/TrEMBL

A0A6Q8PHE3, B4DDD8

Related

ENSP00000411085.2, ENST00000415192.6

Conserved Domains (4) summary

COG0124
Location:56 → 427

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

cd00773
Location:69 → 320

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:334 → 425

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 ...

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...
NM_001289093.2 → NP_001276022.1 histidine--tRNA ligase, cytoplasmic isoform 6

See identical proteins and their annotated locations for NP_001276022.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks three alternate in-frame exons in the 5' coding region, compared to variant 1. The encoded protein (isoform 6) is shorter, compared to isoform 1.

Source sequence(s)

AK303778

Consensus CDS

CCDS75323.1

UniProtKB/TrEMBL

A0A6Q8PHE3, B4E1C5

Related

ENSP00000393244.2, ENST00000431330.7

Conserved Domains (2) summary

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...

cl28413
Location:61 → 387

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
NM_001289094.2 → NP_001276023.1 histidine--tRNA ligase, cytoplasmic isoform 7

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The encoded protein (isoform 7) lacks an internal region and is shorter, compared to isoform 1.

Source sequence(s)

AC116353, AK307669

UniProtKB/TrEMBL

Q52NV4

Conserved Domains (4) summary

COG0124
Location:27 → 472

HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

cd00773
Location:40 → 365

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:379 → 470

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 ...

cl00349
Location:2 → 20

S15_NS1_EPRS_RNA-bind; S15/NS1/EPRS_RNA-binding domain. This short domain consists of a helix-turn-helix structure, which can bind to several types of RNA. It is found in the ribosomal protein S15, the influenza A viral nonstructural protein (NSA) and in several eukaryotic ...
NM_002109.6 → NP_002100.2 histidine--tRNA ligase, cytoplasmic isoform 1

See identical proteins and their annotated locations for NP_002100.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK225776, Z11518

Consensus CDS

CCDS4237.1

UniProtKB/Swiss-Prot

B4DHQ1, B4DY73, D6REN6, J3KNE5, P12081

UniProtKB/TrEMBL

E7ETE2, Q52NV4

Related

ENSP00000425634.1, ENST00000504156.7

Conserved Domains (2) summary

PLN02972
Location:57 → 501

PLN02972; Histidyl-tRNA synthetase

cd00938
Location:5 → 49

HisRS_RNA; HisRS_RNA binding domain. This short RNA-binding domain is found at the N-terminus of HisRS in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). This domain consists of a helix- turn- helix structure, which is similar to other RNA-binding ...