AARS1 alanyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AARS1provided by HGNC
Official Full Name: alanyl-tRNA synthetase 1provided by HGNC
Primary source: HGNC:HGNC:20
See related: Ensembl:ENSG00000090861 MIM:601065; AllianceGenome:HGNC:20
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: AARS; TTD8; CMT2N; DEE29; HDLS2; EIEE29
Summary: The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 59.4), thyroid (RPKM 56.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (70252298..70289506, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (76063291..76100495, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (70286201..70323409, complement)

Chromosome 16 - NC_000016.10 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?

A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations.
Title: A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations.
Clinical characteristics and proteome modifications in two Charcot-Marie-Tooth families with the AARS1 Arg326Trp mutation.
Title: Clinical characteristics and proteome modifications in two Charcot-Marie-Tooth families with the AARS1 Arg326Trp mutation.
Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy.
Title: Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy.
CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.
Title: CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS.
Alanyl-tRNA synthetase 1 (AARS1) gene mutation in a family with intermediate Charcot-Marie-Tooth neuropathy.
Title: Alanyl-tRNA synthetase 1 (AARS1) gene mutation in a family with intermediate Charcot-Marie-Tooth neuropathy.
we investigated the effects of the severe infantile-onset cardiomyopathy-associated R592W mutation of hmtAlaRS on the canonical enzymatic activities of hmtAlaRS. Overall, our results provide fundamental information about tRNA recognition and deepen our understanding of translational quality control mechanisms by hmtAlaRS.
Title: The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase.
all three mutations caused a pathological phenotype of neural abnormalities when expressed in zebrafish, while expression of the human wild-type messenger RNA (mRNA) did not. Our data indicate that not only functional null or hypomorphic alleles, but also hypermorphic AARS alleles can cause dominantly inherited axonal Charcot-Marie-Tooth (CMT) disease .
Title: Hypermorphic and hypomorphic AARS alleles in patients with CMT2N expand clinical and molecular heterogeneities.
A large sequence divergence of the C-terminal domain (C-Ala) reshaped C-Ala in a way that changed the global architecture of alanyl-tRNA synthetase (AlaRS). This reshaping removed the role of C-Ala in prokaryotes for docking tRNA and instead repurposed it to form a dimer interface presenting a DNA-binding groove.
Title: Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS.
Number of missense mutations in AARS expand the clinical spectrum and provide pheno-genotypic correlations in AARS-related neuropathies.
Title: Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland.
A novel mutation in alanyl-tRNA synthetase causes a mild myeloneuropathy, a novel phenotype for patients with mutations in one of the tRNA synthetase genes.
Title: A novel AARS mutation in a family with dominant myeloneuropathy.

Submit: New GeneRIF Correction See all GeneRIFs (16)

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
Charcot-Marie-Tooth disease axonal type 2N MedGen: C2750090 OMIM: 613287 GeneReviews: Not available	Compare labs
Developmental and epileptic encephalopathy, 29 MedGen: C4225361 OMIM: 616339 GeneReviews: Not available	Compare labs
Leukoencephalopathy, hereditary diffuse, with spheroids 2 MedGen: C5562044 OMIM: 619661 GeneReviews: Not available	Compare labs
Trichothiodystrophy 8, nonphotosensitive MedGen: C5562057 OMIM: 619691 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2018-01-11) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2018-01-11) ClinGen Genome Curation Page

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

RH66606 (e-PCR)
- UniSTS:19748

D16S2972 (e-PCR)
- UniSTS:14661

AARS__4231 (e-PCR)
- UniSTS:462704

A002L29 (e-PCR)
- UniSTS:35285

RH65736 (e-PCR)
- UniSTS:75263

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables Ser-tRNA(Ala) hydrolase activity	ISS Inferred from Sequence or Structural Similarity more info
enables alanine-tRNA ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables alanine-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables alanine-tRNA ligase activity	TAS Traceable Author Statement more info
enables amino acid binding	IEA Inferred from Electronic Annotation more info
enables aminoacyl-tRNA editing activity	IBA Inferred from Biological aspect of Ancestor more info
enables aminoacyl-tRNA editing activity	IDA Inferred from Direct Assay more info	PubMed
enables tRNA binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in alanyl-tRNA aminoacylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in alanyl-tRNA aminoacylation	IDA Inferred from Direct Assay more info	PubMed
involved_in alanyl-tRNA aminoacylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aminoacyl-tRNA metabolism involved in translational fidelity	IEA Inferred from Electronic Annotation more info
involved_in cerebellar Purkinje cell layer development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytoplasmic translational fidelity	IEA Inferred from Electronic Annotation more info
involved_in tRNA aminoacylation for protein translation	TAS Traceable Author Statement more info
involved_in tRNA modification	ISS Inferred from Sequence or Structural Similarity more info
involved_in tRNA processing	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: alanine--tRNA ligase, cytoplasmic

Names: alaRS; alanine tRNA ligase 1, cytoplasmic; alanyl-tRNA synthetase, cytoplasmic; renal carcinoma antigen NY-REN-42

NP_001596.2

EC 6.1.1.7

XP_047289622.1

EC 6.1.1.7

XP_054235677.1

EC 6.1.1.7

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_023191.1 RefSeqGene

Range

5001..42116

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_359

mRNA and Protein(s)

NM_001605.3 → NP_001596.2 alanine--tRNA ligase, cytoplasmic

See identical proteins and their annotated locations for NP_001596.2

Status: REVIEWED

Source sequence(s)

AC009060, BC011451, BG764123, BU178772, D32050

Consensus CDS

CCDS32474.1

UniProtKB/Swiss-Prot

A6NF14, B4DR45, P49588, Q53GV7, Q96FA0

UniProtKB/TrEMBL

A0A6Q8PF33

Related

ENSP00000261772.8, ENST00000261772.13

Conserved Domains (5) summary

PLN02900
Location:6 → 961

PLN02900; alanyl-tRNA synthetase

cd00673
Location:7 → 254

AlaRS_core; Alanyl-tRNA synthetase (AlaRS) class II core catalytic domain. AlaRS is a homodimer. It is responsible for the attachment of alanine to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent formation of ...

pfam02272
Location:886 → 955

DHHA1; DHHA1 domain

cl02787
Location:495 → 531

Translation_Factor_II_like; Domain II of Elongation factor Tu (EF-Tu)-like proteins

cl08469
Location:525 → 753

tRNA_SAD; Threonyl and Alanyl tRNA synthetase second additional domain