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LARS1 leucyl-tRNA synthetase 1 [ Homo sapiens (human) ]

Gene ID: 51520, updated on 11-Apr-2024

Summary

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Official Symbol
LARS1provided by HGNC
Official Full Name
leucyl-tRNA synthetase 1provided by HGNC
Primary source
HGNC:HGNC:6512
See related
Ensembl:ENSG00000133706 MIM:151350; AllianceGenome:HGNC:6512
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
LRS; LARS; LEUS; LFIS; cLRS; ILFS1; LEURS; PIG44; RNTLS; HSPC192; hr025Cl
Summary
This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]
Expression
Ubiquitous expression in thyroid (RPKM 24.0), brain (RPKM 19.6) and 25 other tissues See more
Orthologs
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Genomic context

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See LARS1 in Genome Data Viewer
Location:
5q32
Exon count:
32
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (146113034..146182650, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (146647338..146718197, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (145492597..145562213, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986458 Neighboring gene SH3 domain containing ring finger 2 Neighboring gene uncharacterized LOC107986459 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:145428236-145428736 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23358 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr5:145452250-145453204 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr5:145453205-145454157 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81045 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81119 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:145481092-145481650 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81180 Neighboring gene MPRA-validated peak5518 silencer Neighboring gene PLAC8 like 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81226 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81266 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81335 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81447 Neighboring gene ribosomal protein L35a pseudogene 16 Neighboring gene ribosomal protein L35a pseudogene 17 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81571 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81576 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81597 Neighboring gene MPRA-validated peak5520 silencer Neighboring gene MPRA-validated peak5521 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23359 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:145562805-145563651 Neighboring gene Sharpr-MPRA regulatory region 14811 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23360 Neighboring gene RBM27-POU4F3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23361 Neighboring gene Sharpr-MPRA regulatory region 15600 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81701 Neighboring gene RNA binding motif protein 27 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81715 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81725 Neighboring gene RNA, U7 small nuclear 180 pseudogene Neighboring gene MPRA-validated peak5522 silencer Neighboring gene POU class 4 homeobox 3

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
  • 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. Identification of LARS as an essential gene for osteosarcoma proliferation through large-Scale CRISPR-Cas9 screening database and experimental verification. Chen W, et al. J Transl Med, 2022 Aug 12. PMID 35962451, Free PMC Article
  2. O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine. Kim K, et al. Nat Commun, 2022 May 25. PMID 35614056, Free PMC Article
  3. Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization. Tabolacci E, et al. Clin Genet, 2021 Apr. PMID 33314043
  4. Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations. Hirata K, et al. Am J Med Genet A, 2021 Mar. PMID 33300650
  5. Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1. Lenz D, et al. Genet Med, 2020 Nov. PMID 32699352

See all (166) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identification of LARS as an essential gene for osteosarcoma proliferation through large-Scale CRISPR-Cas9 screening database and experimental verification.
    Title: Identification of LARS as an essential gene for osteosarcoma proliferation through large-Scale CRISPR-Cas9 screening database and experimental verification.
  2. O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine.
    Title: O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine.
  3. Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization.
    Title: Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization.
  4. Leucyl-tRNA synthetase 1 is required for proliferation of TSC-null cells.
    Title: Leucyl-tRNA synthetase 1 is required for proliferation of TSC-null cells.
  5. Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
    Title: Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations.
  6. Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
    Title: Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
  7. Molecular basis of the multifaceted functions of human leucyl-tRNA synthetase in protein synthesis and beyond.
    Title: Molecular basis of the multifaceted functions of human leucyl-tRNA synthetase in protein synthesis and beyond.
  8. this study provides evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage.
    Title: Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1.
  9. Leucyl-tRNA synthetase (LRS) is a leucine sensor of the mTORC1 pathway.
    Title: Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction.
  10. The results showed a decrease in autophagy on addition of leucine, demonstrating crosstalk between leucine sensing, LRS translocation, RagD interaction, and mTORC1 activation.
    Title: Leucine-induced localization of Leucyl-tRNA synthetase in lysosome membrane.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Infantile liver failure syndrome 1
MedGen: C3809522 OMIM: 615438 GeneReviews: Not available
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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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Replication interactions

Interaction Pubs
Knockdown of leucyl-tRNA synthetase (LARS) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify leucyl-Trna synthetase (LARS), 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 leucyl-Trna synthetase (LARS), 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 leucyl-Trna synthetase (LARS), 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 leucyl-Trna synthetase (LARS), 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 leucyl-tRNA synthetase (LARS) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses 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

Clone Names

  • FLJ10595, FLJ21788, KIAA1352

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables GTPase activator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables aminoacyl-tRNA editing activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables glutamine-tRNA ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables leucine-tRNA ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables leucine-tRNA ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables leucine-tRNA ligase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in aminoacyl-tRNA metabolism involved in translational fidelity IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to L-leucine IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to amino acid stimulus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to leucine starvation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in glutaminyl-tRNA aminoacylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in leucyl-tRNA aminoacylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in leucyl-tRNA aminoacylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of GTPase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of TOR signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of TORC1 signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of cell size IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in tRNA aminoacylation for protein translation TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
part_of aminoacyl-tRNA synthetase multienzyme complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endomembrane system IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lysosome IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
leucine--tRNA ligase, cytoplasmic
Names
cytoplasmic leucyl-tRNA synthetase
cytosolic leucyl-tRNA synthetase
leucine tRNA ligase 1, cytoplasmic
leucine translase
proliferation-inducing gene 44
NP_001304893.1
NP_001304894.1
NP_057544.2
NP_064502.9
XP_011535958.1
XP_054208781.1

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_042294.1 RefSeqGene

    Range
    5082..74698
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001317964.2 → NP_001304893.1  leucine--tRNA ligase, cytoplasmic isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AB037773, AC091887, AK304134, CK902545, DB091795
    Consensus CDS
    CCDS93798.1
    UniProtKB/TrEMBL
    A0A6I8PL42, B4E266
    Related
    ENSP00000501365.1, ENST00000674270.1
    Conserved Domains (5) summary
    cd07959
    Location:709 → 828
    Anticodon_Ia_Leu_AEc; Anticodon-binding domain of archaeal and eukaryotic cytoplasmic leucyl tRNA synthetases
    cd00812
    Location:479 → 711
    LeuRS_core; catalytic core domain of leucyl-tRNA synthetases
    PLN02959
    Location:5 → 1016
    PLN02959; aminoacyl-tRNA ligase
    cl00015
    Location:45 → 183
    nt_trans; nucleotidyl transferase superfamily
    cl12020
    Location:810 → 859
    Anticodon_Ia_like; Anticodon-binding domain of class Ia aminoacyl tRNA synthetases and similar domains

  2. NM_001317965.2 → NP_001304894.1  leucine--tRNA ligase, cytoplasmic isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate exon in the 5' region and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (4) has a shorter N-terminus than isoform 1.
    Source sequence(s)
    AB037773, AC091887, AK295874, CK902545, DB091795
    Consensus CDS
    CCDS83029.1
    UniProtKB/TrEMBL
    A0A6I8PRS0
    Related
    ENSP00000426005.1, ENST00000510191.5
    Conserved Domains (5) summary
    cd07959
    Location:701 → 820
    Anticodon_Ia_Leu_AEc; Anticodon-binding domain of archaeal and eukaryotic cytoplasmic leucyl tRNA synthetases
    cd00812
    Location:471 → 703
    LeuRS_core; catalytic core domain of leucyl-tRNA synthetases
    PLN02959
    Location:1 → 1008
    PLN02959; aminoacyl-tRNA ligase
    cl00015
    Location:1 → 175
    nt_trans; nucleotidyl transferase superfamily
    cl12020
    Location:802 → 851
    Anticodon_Ia_like; Anticodon-binding domain of class Ia aminoacyl tRNA synthetases and similar domains

  3. NM_016460.4 → NP_057544.2  leucine--tRNA ligase, cytoplasmic isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AB037773, AC091887, AK293750, CK902545, DB091795
    Consensus CDS
    CCDS93797.1
    UniProtKB/TrEMBL
    A0A6I8PIV1, B4DER1
    Related
    ENSP00000501376.1, ENST00000674447.1
    Conserved Domains (5) summary
    cd07959
    Location:728 → 847
    Anticodon_Ia_Leu_AEc; Anticodon-binding domain of archaeal and eukaryotic cytoplasmic leucyl tRNA synthetases
    cd00812
    Location:498 → 730
    LeuRS_core; catalytic core domain of leucyl-tRNA synthetases
    PLN02959
    Location:5 → 1035
    PLN02959; aminoacyl-tRNA ligase
    cl00015
    Location:45 → 202
    nt_trans; nucleotidyl transferase superfamily
    cl12020
    Location:829 → 878
    Anticodon_Ia_like; Anticodon-binding domain of class Ia aminoacyl tRNA synthetases and similar domains

  4. NM_020117.11 → NP_064502.9  leucine--tRNA ligase, cytoplasmic isoform 1

    See identical proteins and their annotated locations for NP_064502.9

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB037773, AC091887, CK902545
    Consensus CDS
    CCDS34265.1
    UniProtKB/Swiss-Prot
    A2RRR4, A7E266, B4DJ10, Q2TU79, Q9NSE1, Q9P2J5
    UniProtKB/TrEMBL
    A0A6I8PIV1
    Related
    ENSP00000377954.2, ENST00000394434.7
    Conserved Domains (1) summary
    cl26128
    Location:5 → 1062
    tRNA-synt_1g; tRNA synthetases class I (M)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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
    146113034..146182650 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011537656.4 → XP_011535958.1  leucine--tRNA ligase, cytoplasmic isoform X1

    See identical proteins and their annotated locations for XP_011535958.1

    UniProtKB/TrEMBL
    A0A6I8PRS0
    Related
    ENSP00000501434.1, ENST00000674174.1
    Conserved Domains (5) summary
    cd07959
    Location:701 → 820
    Anticodon_Ia_Leu_AEc; Anticodon-binding domain of archaeal and eukaryotic cytoplasmic leucyl tRNA synthetases
    cd00812
    Location:471 → 703
    LeuRS_core; catalytic core domain of leucyl-tRNA synthetases
    PLN02959
    Location:1 → 1008
    PLN02959; aminoacyl-tRNA ligase
    cl00015
    Location:1 → 175
    nt_trans; nucleotidyl transferase superfamily
    cl12020
    Location:802 → 851
    Anticodon_Ia_like; Anticodon-binding domain of class Ia aminoacyl tRNA synthetases and similar domains

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    146647338..146718197 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352806.1 → XP_054208781.1  leucine--tRNA ligase, cytoplasmic isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9P2J5.2 GenPept UniProtKB/Swiss-Prot:Q9P2J5

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