Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q9P2J5

- SYLC_HUMAN

UniProt

Q9P2J5 - SYLC_HUMAN

Protein

Leucine--tRNA ligase, cytoplasmic

Gene

LARS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (07 Jun 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs.1 Publication

    Catalytic activityi

    ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu).

    Enzyme regulationi

    (5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole) inhibits LARS by forming a covalent adduct with the 3' adenosine of tRNA(Leu) at the editing site, thus locking the enzyme in an inactive conformation.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei719 – 7191ATPBy similarity

    GO - Molecular functioni

    1. aminoacyl-tRNA editing activity Source: InterPro
    2. ATP binding Source: UniProtKB-KW
    3. leucine-tRNA ligase activity Source: Reactome
    4. protein binding Source: IntAct

    GO - Biological processi

    1. gene expression Source: Reactome
    2. leucyl-tRNA aminoacylation Source: InterPro
    3. tRNA aminoacylation for protein translation Source: Reactome

    Keywords - Molecular functioni

    Aminoacyl-tRNA synthetase, Ligase

    Keywords - Biological processi

    Protein biosynthesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_15306. Cytosolic tRNA aminoacylation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Leucine--tRNA ligase, cytoplasmic (EC:6.1.1.4)
    Alternative name(s):
    Leucyl-tRNA synthetase
    Short name:
    LeuRS
    Gene namesi
    Name:LARS
    Synonyms:KIAA1352
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:6512. LARS.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. nucleus Source: HPA

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Infantile liver failure syndrome 1 (ILFS1) [MIM:615438]: A life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti373 – 3731Y → C in ILFS1. 1 Publication
    VAR_070438

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi615438. phenotype.
    Orphaneti370088. Acute infantile liver failure-multisystemic involvement syndrome.
    PharmGKBiPA30297.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11761176Leucine--tRNA ligase, cytoplasmicPRO_0000152150Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei970 – 9701N6-acetyllysineBy similarity
    Modified residuei1047 – 10471N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ9P2J5.
    PaxDbiQ9P2J5.
    PeptideAtlasiQ9P2J5.
    PRIDEiQ9P2J5.

    PTM databases

    PhosphoSiteiQ9P2J5.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9P2J5.
    BgeeiQ9P2J5.
    CleanExiHS_LARS.
    GenevestigatoriQ9P2J5.

    Organism-specific databases

    HPAiHPA036424.
    HPA040881.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RARSP541363EBI-356077,EBI-355482
    RPTORQ8N1223EBI-356077,EBI-1567928
    RRAGDQ9NQL213EBI-356077,EBI-992949

    Protein-protein interaction databases

    BioGridi119584. 39 interactions.
    IntActiQ9P2J5. 14 interactions.
    MINTiMINT-1158952.
    STRINGi9606.ENSP00000377954.

    Structurei

    Secondary structure

    1
    1176
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi263 – 27412
    Helixi277 – 2826
    Beta strandi287 – 2948
    Helixi296 – 3016
    Beta strandi304 – 3074
    Beta strandi309 – 3113
    Beta strandi314 – 3174
    Beta strandi323 – 3264
    Helixi328 – 3358
    Turni336 – 3383
    Beta strandi339 – 3424
    Beta strandi348 – 3514
    Helixi354 – 3574
    Beta strandi361 – 3633
    Beta strandi368 – 3703
    Beta strandi372 – 3765
    Beta strandi382 – 3854
    Beta strandi387 – 3915
    Turni393 – 3953
    Helixi397 – 40812
    Helixi411 – 4144
    Turni415 – 4173
    Helixi420 – 4223
    Turni423 – 4253
    Beta strandi432 – 4343
    Turni435 – 4373
    Beta strandi438 – 4403
    Helixi441 – 4488
    Helixi457 – 47418
    Helixi487 – 50014
    Beta strandi503 – 5086

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2WFDX-ray3.25A/B260-509[»]
    ProteinModelPortaliQ9P2J5.
    SMRiQ9P2J5. Positions 13-910.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9P2J5.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni260 – 509250Editing domainAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi53 – 6311"HIGH" regionAdd
    BLAST
    Motifi716 – 7205"KMSKS" region

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0495.
    HOGENOMiHOG000216621.
    HOVERGENiHBG055325.
    InParanoidiQ9P2J5.
    KOiK01869.
    OMAiYEGVMLV.
    OrthoDBiEOG7VB2DJ.
    PhylomeDBiQ9P2J5.
    TreeFamiTF105718.

    Family and domain databases

    Gene3Di1.10.730.10. 1 hit.
    3.40.50.620. 3 hits.
    3.90.740.10. 1 hit.
    InterProiIPR001412. aa-tRNA-synth_I_CS.
    IPR002300. aa-tRNA-synth_Ia.
    IPR004493. Leu-tRNA-synth_Ia_arc/euk.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_1a_anticodon-bd.
    IPR013155. V/L/I-tRNA-synth_anticodon-bd.
    IPR009008. Val/Leu/Ile-tRNA-synth_edit.
    [Graphical view]
    PfamiPF08264. Anticodon_1. 1 hit.
    PF00133. tRNA-synt_1. 2 hits.
    [Graphical view]
    SUPFAMiSSF47323. SSF47323. 1 hit.
    SSF50677. SSF50677. 2 hits.
    TIGRFAMsiTIGR00395. leuS_arch. 1 hit.
    PROSITEiPS00178. AA_TRNA_LIGASE_I. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9P2J5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF     50
    PYPYMNGRLH LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC 100
    ADKLKREIEL YGCPPDFPDE EEEEEETSVK TEDIIIKDKA KGKKSKAAAK 150
    AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW LDYFPPLAIQ DLKRMGLKVD 200
    WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY SPKDGQPCMD 250
    HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF 300
    GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK 350
    ELMGEEILGA SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI 400
    AALRDLKKKQ ALRAKYGIRD DMVLPFEPVP VIEIPGFGNL SAVTICDELK 450
    IQSQNDREKL AEAKEKIYLK GFYEGIMLVD GFKGQKVQDV KKTIQKKMID 500
    AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK KQTSQCLKNL 550
    ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY 600
    MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI 650
    AKEKLDQLKQ EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW 700
    PTAVRANGHL LLNSEKMSKS TGNFLTLTQA IDKFSADGMR LALADAGDTV 750
    EDANFVEAMA DAGILRLYTW VEWVKEMVAN WDSLRSGPAS TFNDRVFASE 800
    LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV EGMHRELVFR 850
    FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ 900
    YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT 950
    TLSVLRKHFE ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL 1000
    EKMGPRILDL QLEFDEKAVL MENIVYLTNS LELEHIEVKF ASEAEDKIRE 1050
    DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH FSTKIEIRQG DNCDSIIRRL 1100
    MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP ISEHAVFNVD 1150
    LMSKKIHLTE NGIRVDIGDT IIYLVH 1176
    Length:1,176
    Mass (Da):134,466
    Last modified:June 7, 2004 - v2
    Checksum:i44A4D1A1EF31634A
    GO

    Sequence cautioni

    The sequence BAA92590.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti271 – 2711V → A in BAA95667. 1 PublicationCurated
    Sequence conflicti892 – 8921N → D in BAA95667. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti82 – 821K → R.1 Publication
    Corresponds to variant rs112954500 [ dbSNP | Ensembl ].
    VAR_070437
    Natural varianti373 – 3731Y → C in ILFS1. 1 Publication
    VAR_070438
    Natural varianti1088 – 10881R → K.1 Publication
    Corresponds to variant rs10988 [ dbSNP | Ensembl ].
    VAR_052637

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D84223 mRNA. Translation: BAA95667.1.
    AB037773 mRNA. Translation: BAA92590.1. Different initiation.
    CH471062 Genomic DNA. Translation: EAW61848.1.
    BC150213 mRNA. Translation: AAI50214.1.
    BC151214 mRNA. Translation: AAI51215.1.
    BC152422 mRNA. Translation: AAI52423.1.
    CCDSiCCDS34265.1.
    RefSeqiNP_064502.9. NM_020117.9.
    UniGeneiHs.432674.

    Genome annotation databases

    EnsembliENST00000394434; ENSP00000377954; ENSG00000133706.
    GeneIDi51520.
    KEGGihsa:51520.
    UCSCiuc003lnx.1. human.

    Polymorphism databases

    DMDMi48428689.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D84223 mRNA. Translation: BAA95667.1 .
    AB037773 mRNA. Translation: BAA92590.1 . Different initiation.
    CH471062 Genomic DNA. Translation: EAW61848.1 .
    BC150213 mRNA. Translation: AAI50214.1 .
    BC151214 mRNA. Translation: AAI51215.1 .
    BC152422 mRNA. Translation: AAI52423.1 .
    CCDSi CCDS34265.1.
    RefSeqi NP_064502.9. NM_020117.9.
    UniGenei Hs.432674.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2WFD X-ray 3.25 A/B 260-509 [» ]
    ProteinModelPortali Q9P2J5.
    SMRi Q9P2J5. Positions 13-910.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119584. 39 interactions.
    IntActi Q9P2J5. 14 interactions.
    MINTi MINT-1158952.
    STRINGi 9606.ENSP00000377954.

    Chemistry

    BindingDBi Q9P2J5.
    ChEMBLi CHEMBL3258.
    DrugBanki DB00149. L-Leucine.

    PTM databases

    PhosphoSitei Q9P2J5.

    Polymorphism databases

    DMDMi 48428689.

    Proteomic databases

    MaxQBi Q9P2J5.
    PaxDbi Q9P2J5.
    PeptideAtlasi Q9P2J5.
    PRIDEi Q9P2J5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000394434 ; ENSP00000377954 ; ENSG00000133706 .
    GeneIDi 51520.
    KEGGi hsa:51520.
    UCSCi uc003lnx.1. human.

    Organism-specific databases

    CTDi 51520.
    GeneCardsi GC05M145473.
    HGNCi HGNC:6512. LARS.
    HPAi HPA036424.
    HPA040881.
    MIMi 151350. gene.
    615438. phenotype.
    neXtProti NX_Q9P2J5.
    Orphaneti 370088. Acute infantile liver failure-multisystemic involvement syndrome.
    PharmGKBi PA30297.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0495.
    HOGENOMi HOG000216621.
    HOVERGENi HBG055325.
    InParanoidi Q9P2J5.
    KOi K01869.
    OMAi YEGVMLV.
    OrthoDBi EOG7VB2DJ.
    PhylomeDBi Q9P2J5.
    TreeFami TF105718.

    Enzyme and pathway databases

    Reactomei REACT_15306. Cytosolic tRNA aminoacylation.

    Miscellaneous databases

    ChiTaRSi LARS. human.
    EvolutionaryTracei Q9P2J5.
    GeneWikii Leucyl-tRNA_synthetase.
    GenomeRNAii 51520.
    NextBioi 55220.
    PROi Q9P2J5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9P2J5.
    Bgeei Q9P2J5.
    CleanExi HS_LARS.
    Genevestigatori Q9P2J5.

    Family and domain databases

    Gene3Di 1.10.730.10. 1 hit.
    3.40.50.620. 3 hits.
    3.90.740.10. 1 hit.
    InterProi IPR001412. aa-tRNA-synth_I_CS.
    IPR002300. aa-tRNA-synth_Ia.
    IPR004493. Leu-tRNA-synth_Ia_arc/euk.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_1a_anticodon-bd.
    IPR013155. V/L/I-tRNA-synth_anticodon-bd.
    IPR009008. Val/Leu/Ile-tRNA-synth_edit.
    [Graphical view ]
    Pfami PF08264. Anticodon_1. 1 hit.
    PF00133. tRNA-synt_1. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47323. SSF47323. 1 hit.
    SSF50677. SSF50677. 2 hits.
    TIGRFAMsi TIGR00395. leuS_arch. 1 hit.
    PROSITEi PS00178. AA_TRNA_LIGASE_I. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and sequence determination of a human cytoplasmic leucyl-tRNA synthetase gene."
      Motegi H., Noda T., Shiba K.
      Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-1088.
      Tissue: Brain.
    2. "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
      DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    6. "Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles."
      Seiradake E., Mao W., Hernandez V., Baker S.J., Plattner J.J., Alley M.R.K., Cusack S.
      J. Mol. Biol. 390:196-207(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 260-509 IN COMPLEX WITH (6-(ETHYLAMINO)-5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL) AND AMP, FUNCTION.
    7. Cited for: VARIANT ILFS1 CYS-373, VARIANT ARG-82.

    Entry informationi

    Entry nameiSYLC_HUMAN
    AccessioniPrimary (citable) accession number: Q9P2J5
    Secondary accession number(s): A7E266, Q9NSE1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2004
    Last sequence update: June 7, 2004
    Last modified: October 1, 2014
    This is version 120 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Aminoacyl-tRNA synthetases
      List of aminoacyl-tRNA synthetase entries
    2. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3