DARS1 aspartyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DARS1provided by HGNC
Official Full Name: aspartyl-tRNA synthetase 1provided by HGNC
Primary source: HGNC:HGNC:2678
See related: Ensembl:ENSG00000115866 MIM:603084; AllianceGenome:HGNC:2678
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: DARS; HBSL; aspRS
Summary: This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyelination with brainstem and spinal cord involvement and leg spasticity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
Expression: Ubiquitous expression in thyroid (RPKM 24.7), lymph node (RPKM 20.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q21.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (135905881..135985684, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (136350305..136430110, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (136663451..136743254, complement)

Chromosome 2 - NC_000002.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment.
Title: DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment.
Functional genomics screening identifies aspartyl-tRNA synthetase as a novel prognostic marker and a therapeutic target for gastric cancers.
Title: Functional genomics screening identifies aspartyl-tRNA synthetase as a novel prognostic marker and a therapeutic target for gastric cancers.
Developmental delay and late onset HBSL pathology in hypomorphic Dars1(M256L) mice.
Title: Developmental delay and late onset HBSL pathology in hypomorphic Dars1(M256L) mice.
This study demonstrates that human mitochondrial AspRS, ArgRS, and LysRS, each have a specific sub-mitochondrial distribution, with ArgRS being exclusively localized in the membrane, LysRS exclusively in the soluble fraction, and AspRS being present in both.
Title: Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations.
Genetic variants of the DARS gene may influence individual susceptibility to isolated VSD in Chinese Han population. Risk of VSD was significantly associated with rs2164331 [G/A; odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.69-0.91; P = 3.17 x 10(-3)], rs6738266 [G/A; OR = 1.17, 95% CI = 1.05-1.29, P = 1.83 x 10(-3)], and rs309143 [G/A; OR = 1.09, 95% CI = 1.01-1.17; P = 3.12 x 10(-2)].
Title: Association of DARS gene polymorphisms with the risk of isolated ventricular septal defects in the Chinese Han population.
Report on the crystal structure of human cytosolic aspartyl-tRNA synthetase (DRS) at a resolution of 2.25 A.
Title: Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex.
Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity.
Title: Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity.
the N-terminus shows a less-ordered structure with flexible beta-turn, suggesting that when tRNA is stretched, the dissociation rate of Asp-tRNA from aspartyl-tRNA synthetase is reduced, giving time for elongation factor 1alpha to interact with Asp-tRNA.
Title: Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function.

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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
Hypomyelination with brain stem and spinal cord involvement and leg spasticity MedGen: C4755254 OMIM: 615281 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify aspartyl-tRNA synthetase (DARS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify aspartyl-tRNA synthetase (DARS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify aspartyl-tRNA synthetase (DARS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify aspartyl-tRNA synthetase (DARS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
matrix	gag	HIV-1 MA is identified to have a physical interaction with aspartyl-tRNA synthetase (DARS) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

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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

D2S2723 (e-PCR)
- UniSTS:79741

STS-AA018181 (e-PCR)
- UniSTS:18883

RH17849 (e-PCR)
- UniSTS:50884

SHGC-3975 (e-PCR)
- UniSTS:30671

Dars (e-PCR), detects polymorphism
- UniSTS:506835

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 aminoacylase activity	TAS Traceable Author Statement more info	PubMed
enables aspartate-tRNA ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in aspartyl-tRNA aminoacylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in translation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of aminoacyl-tRNA synthetase multienzyme complex	IBA Inferred from Biological aspect of Ancestor more info
part_of aminoacyl-tRNA synthetase multienzyme complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement 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	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: aspartate--tRNA ligase, cytoplasmic

Names: aspartate tRNA ligase 1, cytoplasmic; aspartyl-tRNA synthetase, cytoplasmic; cell proliferation-inducing gene 40 protein; testicular tissue protein Li 192

NP_001280241.1

EC 6.1.1.12

NP_001340.2

EC 6.1.1.12

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_034149.1 RefSeqGene

Range

5059..84804

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001293312.1 → NP_001280241.1 aspartate--tRNA ligase, cytoplasmic isoform 2

See identical proteins and their annotated locations for NP_001280241.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.

Source sequence(s)

AC011999, BC000629, BU615302, BX101357, CR749809, DA597505

Conserved Domains (3) summary

cd00776
Location:74 → 397

AsxRS_core; Asx tRNA synthetase (AspRS/AsnRS) class II core domain. Assignment to class II aminoacyl-tRNA synthetases (aaRS) based upon its structure and the presence of three characteristic sequence motifs in the core domain. This family includes AsnRS as well as ...

cd04320
Location:1 → 58

AspRS_cyto_N; AspRS_cyto_N: N-terminal, anticodon recognition domain of the type found in Saccharomyces cerevisiae and human cytoplasmic aspartyl-tRNA synthetase (AspRS). This domain is a beta-barrel domain (OB fold) involved in binding the tRNA anticodon stem-loop. ...

pfam00152
Location:75 → 395

tRNA-synt_2; tRNA synthetases class II (D, K and N)
NM_001349.4 → NP_001340.2 aspartate--tRNA ligase, cytoplasmic isoform 1

See identical proteins and their annotated locations for NP_001340.2

Status: REVIEWED

Description

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

Source sequence(s)

AC011999, BC000629, BU615302, BX101357, DA597505

Consensus CDS

CCDS2180.1

UniProtKB/Swiss-Prot

A8K3J2, D3DP77, P14868, Q2TNI3, Q32Q69, Q53HV4, Q53YC5, Q68CR9, Q9BW52

UniProtKB/TrEMBL

A0A140VJW5

Related

ENSP00000264161.4, ENST00000264161.9

Conserved Domains (1) summary

cl27743
Location:3 → 501

tRNA-synt_2; tRNA synthetases class II (D, K and N)