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Q9P2J5

- SYLC_HUMAN

UniProt

Q9P2J5 - SYLC_HUMAN

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Protein

Leucine--tRNA ligase, cytoplasmic

Gene

LARS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

GO - Biological processi

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

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
Complete GO annotation...

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

BgeeiQ9P2J5.
CleanExiHS_LARS.
ExpressionAtlasiQ9P2J5. baseline and differential.
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. 43 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 – 27412Combined sources
Helixi277 – 2826Combined sources
Beta strandi287 – 2948Combined sources
Helixi296 – 3016Combined sources
Beta strandi304 – 3074Combined sources
Beta strandi309 – 3113Combined sources
Beta strandi314 – 3174Combined sources
Beta strandi323 – 3264Combined sources
Helixi328 – 3358Combined sources
Turni336 – 3383Combined sources
Beta strandi339 – 3424Combined sources
Beta strandi348 – 3514Combined sources
Helixi354 – 3574Combined sources
Beta strandi361 – 3633Combined sources
Beta strandi368 – 3703Combined sources
Beta strandi372 – 3765Combined sources
Beta strandi382 – 3854Combined sources
Beta strandi387 – 3915Combined sources
Turni393 – 3953Combined sources
Helixi397 – 40812Combined sources
Helixi411 – 4144Combined sources
Turni415 – 4173Combined sources
Helixi420 – 4223Combined sources
Turni423 – 4253Combined sources
Beta strandi432 – 4343Combined sources
Turni435 – 4373Combined sources
Beta strandi438 – 4403Combined sources
Helixi441 – 4488Combined sources
Helixi457 – 47418Combined sources
Helixi487 – 50014Combined sources
Beta strandi503 – 5086Combined sources

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.
GeneTreeiENSGT00390000012163.
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

        10         20         30         40         50
MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF
60 70 80 90 100
PYPYMNGRLH LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC
110 120 130 140 150
ADKLKREIEL YGCPPDFPDE EEEEEETSVK TEDIIIKDKA KGKKSKAAAK
160 170 180 190 200
AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW LDYFPPLAIQ DLKRMGLKVD
210 220 230 240 250
WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY SPKDGQPCMD
260 270 280 290 300
HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF
310 320 330 340 350
GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK
360 370 380 390 400
ELMGEEILGA SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI
410 420 430 440 450
AALRDLKKKQ ALRAKYGIRD DMVLPFEPVP VIEIPGFGNL SAVTICDELK
460 470 480 490 500
IQSQNDREKL AEAKEKIYLK GFYEGIMLVD GFKGQKVQDV KKTIQKKMID
510 520 530 540 550
AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK KQTSQCLKNL
560 570 580 590 600
ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY
610 620 630 640 650
MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI
660 670 680 690 700
AKEKLDQLKQ EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW
710 720 730 740 750
PTAVRANGHL LLNSEKMSKS TGNFLTLTQA IDKFSADGMR LALADAGDTV
760 770 780 790 800
EDANFVEAMA DAGILRLYTW VEWVKEMVAN WDSLRSGPAS TFNDRVFASE
810 820 830 840 850
LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV EGMHRELVFR
860 870 880 890 900
FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ
910 920 930 940 950
YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT
960 970 980 990 1000
TLSVLRKHFE ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL
1010 1020 1030 1040 1050
EKMGPRILDL QLEFDEKAVL MENIVYLTNS LELEHIEVKF ASEAEDKIRE
1060 1070 1080 1090 1100
DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH FSTKIEIRQG DNCDSIIRRL
1110 1120 1130 1140 1150
MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP ISEHAVFNVD
1160 1170
LMSKKIHLTE NGIRVDIGDT IIYLVH
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. 43 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.
GeneTreei ENSGT00390000012163.
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

Bgeei Q9P2J5.
CleanExi HS_LARS.
ExpressionAtlasi Q9P2J5. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 121 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