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

    Gene ID: 51520, updated on 3-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (146113034..146182650, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (146647338..146718197, complement)
    RS_2024_09 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 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. 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
    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. A novel mutation in the mitochondrial DNA tRNA Leu (UUR) gene associated with late-onset ocular myopathy. Maeso E, et al. Neuromuscul Disord, 2007 May. PMID 17363246
    4. 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
    5. Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis. Shin SH, et al. Exp Mol Med, 2008 Apr 30. PMID 18446061, Free PMC Article

    See all (191) 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
    		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)

    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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    NEW Try the new Transcript table

    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_2024_08

    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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