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Q9P2J5 (SYLC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leucine--tRNA ligase, cytoplasmic

EC=6.1.1.4
Alternative name(s):
Leucyl-tRNA synthetase
Short name=LeuRS
Gene names
Name:LARS
Synonyms:KIAA1352
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1176 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Catalytic activity

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

Enzyme regulation

(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.

Subcellular location

Cytoplasm By similarity.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the class-I aminoacyl-tRNA synthetase family.

Sequence caution

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

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11761176Leucine--tRNA ligase, cytoplasmic
PRO_0000152150

Regions

Region260 – 509250Editing domain
Motif53 – 6311"HIGH" region
Motif716 – 7205"KMSKS" region

Sites

Binding site7191ATP By similarity

Amino acid modifications

Modified residue9701N6-acetyllysine By similarity
Modified residue10471N6-acetyllysine By similarity

Natural variations

Natural variant821K → R. Ref.7
Corresponds to variant rs112954500 [ dbSNP | Ensembl ].
VAR_070437
Natural variant3731Y → C in ILFS1. Ref.7
VAR_070438
Natural variant10881R → K. Ref.1
Corresponds to variant rs10988 [ dbSNP | Ensembl ].
VAR_052637

Experimental info

Sequence conflict2711V → A in BAA95667. Ref.1
Sequence conflict8921N → D in BAA95667. Ref.1

Secondary structure

........................................................ 1176
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9P2J5 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: 44A4D1A1EF31634A

FASTA1,176134,466
        10         20         30         40         50         60 
MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF PYPYMNGRLH 

        70         80         90        100        110        120 
LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE 

       130        140        150        160        170        180 
EEEEEETSVK TEDIIIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW 

       190        200        210        220        230        240 
LDYFPPLAIQ DLKRMGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY 

       250        260        270        280        290        300 
SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF 

       310        320        330        340        350        360 
GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK ELMGEEILGA 

       370        380        390        400        410        420 
SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI AALRDLKKKQ ALRAKYGIRD 

       430        440        450        460        470        480 
DMVLPFEPVP VIEIPGFGNL SAVTICDELK IQSQNDREKL AEAKEKIYLK GFYEGIMLVD 

       490        500        510        520        530        540 
GFKGQKVQDV KKTIQKKMID AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK 

       550        560        570        580        590        600 
KQTSQCLKNL ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY 

       610        620        630        640        650        660 
MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI AKEKLDQLKQ 

       670        680        690        700        710        720 
EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW PTAVRANGHL LLNSEKMSKS 

       730        740        750        760        770        780 
TGNFLTLTQA IDKFSADGMR LALADAGDTV EDANFVEAMA DAGILRLYTW VEWVKEMVAN 

       790        800        810        820        830        840 
WDSLRSGPAS TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV 

       850        860        870        880        890        900 
EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ 

       910        920        930        940        950        960 
YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE 

       970        980        990       1000       1010       1020 
ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL 

      1030       1040       1050       1060       1070       1080 
MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH 

      1090       1100       1110       1120       1130       1140 
FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP 

      1150       1160       1170 
ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"Identification of a mutation in LARS as a novel cause of infantile hepatopathy."
Casey J.P., McGettigan P., Lynam-Lennon N., McDermott M., Regan R., Conroy J., Bourke B., O'Sullivan J., Crushell E., Lynch S., Ennis S.
Mol. Genet. Metab. 106:351-358(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILFS1 CYS-373, VARIANT ARG-82.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS34265.1.
RefSeqNP_064502.9. NM_020117.9.
UniGeneHs.432674.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WFDX-ray3.25A/B260-509[»]
ProteinModelPortalQ9P2J5.
SMRQ9P2J5. Positions 13-910.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119584. 41 interactions.
IntActQ9P2J5. 14 interactions.
MINTMINT-1158952.
STRING9606.ENSP00000377954.

Chemistry

BindingDBQ9P2J5.
ChEMBLCHEMBL3258.
DrugBankDB00149. L-Leucine.

PTM databases

PhosphoSiteQ9P2J5.

Polymorphism databases

DMDM48428689.

Proteomic databases

MaxQBQ9P2J5.
PaxDbQ9P2J5.
PeptideAtlasQ9P2J5.
PRIDEQ9P2J5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394434; ENSP00000377954; ENSG00000133706.
GeneID51520.
KEGGhsa:51520.
UCSCuc003lnx.1. human.

Organism-specific databases

CTD51520.
GeneCardsGC05M145473.
HGNCHGNC:6512. LARS.
HPAHPA036424.
HPA040881.
MIM151350. gene.
615438. phenotype.
neXtProtNX_Q9P2J5.
Orphanet370088. Acute infantile liver failure-multisystemic involvement syndrome.
PharmGKBPA30297.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0495.
HOGENOMHOG000216621.
HOVERGENHBG055325.
InParanoidQ9P2J5.
KOK01869.
OMAYEGVMLV.
OrthoDBEOG7VB2DJ.
PhylomeDBQ9P2J5.
TreeFamTF105718.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9P2J5.
BgeeQ9P2J5.
CleanExHS_LARS.
GenevestigatorQ9P2J5.

Family and domain databases

Gene3D1.10.730.10. 1 hit.
3.40.50.620. 3 hits.
3.90.740.10. 1 hit.
InterProIPR001412. 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]
PfamPF08264. Anticodon_1. 1 hit.
PF00133. tRNA-synt_1. 2 hits.
[Graphical view]
SUPFAMSSF47323. SSF47323. 1 hit.
SSF50677. SSF50677. 2 hits.
TIGRFAMsTIGR00395. leuS_arch. 1 hit.
PROSITEPS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLARS. human.
EvolutionaryTraceQ9P2J5.
GeneWikiLeucyl-tRNA_synthetase.
GenomeRNAi51520.
NextBio55220.
PROQ9P2J5.
SOURCESearch...

Entry information

Entry nameSYLC_HUMAN
AccessionPrimary (citable) accession number: Q9P2J5
Secondary accession number(s): A7E266, Q9NSE1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: July 9, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries