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Protein

Leucine--tRNA ligase, cytoplasmic

Gene

LARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei719ATPBy similarity1

GO - Molecular functioni

GO - Biological processi

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

BioCyciZFISH:HS05781-MONOMER.
BRENDAi6.1.1.4. 2681.
ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
R-HSA-379716. Cytosolic tRNA aminoacylation.

Protein family/group databases

MoonProtiQ9P2J5.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6512. LARS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Infantile liver failure syndrome 1 (ILFS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615438
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070438373Y → C in ILFS1. 1 PublicationCorresponds to variant rs201861847dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi51520.
MalaCardsiLARS.
MIMi615438. phenotype.
OpenTargetsiENSG00000133706.
Orphaneti370088. Acute infantile liver failure-multisystemic involvement syndrome.
PharmGKBiPA30297.

Chemistry databases

ChEMBLiCHEMBL3258.
DrugBankiDB00149. L-Leucine.

Polymorphism and mutation databases

BioMutaiLARS.
DMDMi48428689.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001521501 – 1176Leucine--tRNA ligase, cytoplasmicAdd BLAST1176

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei167PhosphoserineCombined sources1
Modified residuei720PhosphoserineCombined sources1
Modified residuei970N6-acetyllysineBy similarity1
Modified residuei1047N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9P2J5.
MaxQBiQ9P2J5.
PaxDbiQ9P2J5.
PeptideAtlasiQ9P2J5.
PRIDEiQ9P2J5.

PTM databases

iPTMnetiQ9P2J5.
PhosphoSitePlusiQ9P2J5.
SwissPalmiQ9P2J5.

Expressioni

Gene expression databases

BgeeiENSG00000133706.
CleanExiHS_LARS.
ExpressionAtlasiQ9P2J5. baseline and differential.
GenevisibleiQ9P2J5. HS.

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. 70 interactors.
IntActiQ9P2J5. 25 interactors.
MINTiMINT-1158952.
STRINGi9606.ENSP00000377954.

Chemistry databases

BindingDBiQ9P2J5.

Structurei

Secondary structure

11176
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi263 – 274Combined sources12
Helixi277 – 282Combined sources6
Beta strandi287 – 294Combined sources8
Helixi296 – 301Combined sources6
Beta strandi304 – 307Combined sources4
Beta strandi309 – 311Combined sources3
Beta strandi314 – 317Combined sources4
Beta strandi323 – 326Combined sources4
Helixi328 – 335Combined sources8
Turni336 – 338Combined sources3
Beta strandi339 – 342Combined sources4
Beta strandi348 – 351Combined sources4
Helixi354 – 357Combined sources4
Beta strandi361 – 363Combined sources3
Beta strandi368 – 370Combined sources3
Beta strandi372 – 376Combined sources5
Beta strandi382 – 385Combined sources4
Beta strandi387 – 391Combined sources5
Turni393 – 395Combined sources3
Helixi397 – 408Combined sources12
Helixi411 – 414Combined sources4
Turni415 – 417Combined sources3
Helixi420 – 422Combined sources3
Turni423 – 425Combined sources3
Beta strandi432 – 434Combined sources3
Turni435 – 437Combined sources3
Beta strandi438 – 440Combined sources3
Helixi441 – 448Combined sources8
Helixi457 – 474Combined sources18
Helixi487 – 500Combined sources14
Beta strandi503 – 508Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WFDX-ray3.25A/B260-509[»]
ProteinModelPortaliQ9P2J5.
SMRiQ9P2J5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9P2J5.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni260 – 509Editing domainAdd BLAST250

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi53 – 63"HIGH" regionAdd BLAST11
Motifi716 – 720"KMSKS" region5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0437. Eukaryota.
COG0495. LUCA.
GeneTreeiENSGT00390000012163.
HOGENOMiHOG000216621.
HOVERGENiHBG055325.
InParanoidiQ9P2J5.
KOiK01869.
OMAiFYITTCA.
OrthoDBiEOG091G01VH.
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.
IPR013155. M/V/L/I-tRNA-synth_anticd-bd.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_Ia_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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9P2J5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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
Isoform 2 (identifier: Q9P2J5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.

Note: No experimental confirmation available.
Show »
Length:1,122
Mass (Da):128,038
Checksum:i87D1D1210F7A2252
GO
Isoform 3 (identifier: Q9P2J5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-691: Missing.

Note: No experimental confirmation available.
Show »
Length:485
Mass (Da):55,295
Checksum:iE4C99F943B951653
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti271V → A in BAA95667 (Ref. 1) Curated1
Sequence conflicti892N → D in BAA95667 (Ref. 1) Curated1
Sequence conflicti1026Y → C in AAI31799 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07043782K → R.1 PublicationCorresponds to variant rs112954500dbSNPEnsembl.1
Natural variantiVAR_070438373Y → C in ILFS1. 1 PublicationCorresponds to variant rs201861847dbSNPEnsembl.1
Natural variantiVAR_0526371088R → K.1 PublicationCorresponds to variant rs10988dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0572041 – 691Missing in isoform 3. 2 PublicationsAdd BLAST691
Alternative sequenceiVSP_0572051 – 54Missing in isoform 2. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84223 mRNA. Translation: BAA95667.1.
AB037773 mRNA. Translation: BAA92590.1. Different initiation.
AY513284 mRNA. Translation: AAT08037.1.
AY926480 mRNA. Translation: AAX10025.1.
AK295874 mRNA. Translation: BAG58672.1.
AC091887 Genomic DNA. No translation available.
AC091959 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61848.1.
BC131798 mRNA. Translation: AAI31799.1.
BC150213 mRNA. Translation: AAI50214.1.
BC151214 mRNA. Translation: AAI51215.1.
BC152422 mRNA. Translation: AAI52423.1.
CCDSiCCDS34265.1. [Q9P2J5-1]
CCDS83029.1. [Q9P2J5-2]
RefSeqiNP_001304893.1. NM_001317964.1.
NP_001304894.1. NM_001317965.1. [Q9P2J5-2]
NP_057544.2. NM_016460.3.
NP_064502.9. NM_020117.10. [Q9P2J5-1]
XP_011535958.1. XM_011537656.2. [Q9P2J5-2]
UniGeneiHs.432674.

Genome annotation databases

EnsembliENST00000274562; ENSP00000274562; ENSG00000133706. [Q9P2J5-3]
ENST00000394434; ENSP00000377954; ENSG00000133706. [Q9P2J5-1]
ENST00000510191; ENSP00000426005; ENSG00000133706. [Q9P2J5-2]
GeneIDi51520.
KEGGihsa:51520.
UCSCiuc003lnx.2. human. [Q9P2J5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84223 mRNA. Translation: BAA95667.1.
AB037773 mRNA. Translation: BAA92590.1. Different initiation.
AY513284 mRNA. Translation: AAT08037.1.
AY926480 mRNA. Translation: AAX10025.1.
AK295874 mRNA. Translation: BAG58672.1.
AC091887 Genomic DNA. No translation available.
AC091959 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61848.1.
BC131798 mRNA. Translation: AAI31799.1.
BC150213 mRNA. Translation: AAI50214.1.
BC151214 mRNA. Translation: AAI51215.1.
BC152422 mRNA. Translation: AAI52423.1.
CCDSiCCDS34265.1. [Q9P2J5-1]
CCDS83029.1. [Q9P2J5-2]
RefSeqiNP_001304893.1. NM_001317964.1.
NP_001304894.1. NM_001317965.1. [Q9P2J5-2]
NP_057544.2. NM_016460.3.
NP_064502.9. NM_020117.10. [Q9P2J5-1]
XP_011535958.1. XM_011537656.2. [Q9P2J5-2]
UniGeneiHs.432674.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WFDX-ray3.25A/B260-509[»]
ProteinModelPortaliQ9P2J5.
SMRiQ9P2J5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119584. 70 interactors.
IntActiQ9P2J5. 25 interactors.
MINTiMINT-1158952.
STRINGi9606.ENSP00000377954.

Chemistry databases

BindingDBiQ9P2J5.
ChEMBLiCHEMBL3258.
DrugBankiDB00149. L-Leucine.

Protein family/group databases

MoonProtiQ9P2J5.

PTM databases

iPTMnetiQ9P2J5.
PhosphoSitePlusiQ9P2J5.
SwissPalmiQ9P2J5.

Polymorphism and mutation databases

BioMutaiLARS.
DMDMi48428689.

Proteomic databases

EPDiQ9P2J5.
MaxQBiQ9P2J5.
PaxDbiQ9P2J5.
PeptideAtlasiQ9P2J5.
PRIDEiQ9P2J5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274562; ENSP00000274562; ENSG00000133706. [Q9P2J5-3]
ENST00000394434; ENSP00000377954; ENSG00000133706. [Q9P2J5-1]
ENST00000510191; ENSP00000426005; ENSG00000133706. [Q9P2J5-2]
GeneIDi51520.
KEGGihsa:51520.
UCSCiuc003lnx.2. human. [Q9P2J5-1]

Organism-specific databases

CTDi51520.
DisGeNETi51520.
GeneCardsiLARS.
HGNCiHGNC:6512. LARS.
HPAiHPA036424.
HPA040881.
MalaCardsiLARS.
MIMi151350. gene.
615438. phenotype.
neXtProtiNX_Q9P2J5.
OpenTargetsiENSG00000133706.
Orphaneti370088. Acute infantile liver failure-multisystemic involvement syndrome.
PharmGKBiPA30297.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0437. Eukaryota.
COG0495. LUCA.
GeneTreeiENSGT00390000012163.
HOGENOMiHOG000216621.
HOVERGENiHBG055325.
InParanoidiQ9P2J5.
KOiK01869.
OMAiFYITTCA.
OrthoDBiEOG091G01VH.
PhylomeDBiQ9P2J5.
TreeFamiTF105718.

Enzyme and pathway databases

BioCyciZFISH:HS05781-MONOMER.
BRENDAi6.1.1.4. 2681.
ReactomeiR-HSA-2408517. SeMet incorporation into proteins.
R-HSA-379716. Cytosolic tRNA aminoacylation.

Miscellaneous databases

ChiTaRSiLARS. human.
EvolutionaryTraceiQ9P2J5.
GeneWikiiLeucyl-tRNA_synthetase.
GenomeRNAii51520.
PROiQ9P2J5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133706.
CleanExiHS_LARS.
ExpressionAtlasiQ9P2J5. baseline and differential.
GenevisibleiQ9P2J5. HS.

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.
IPR013155. M/V/L/I-tRNA-synth_anticd-bd.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_Ia_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]
ProtoNetiSearch...

Entry informationi

Entry nameiSYLC_HUMAN
AccessioniPrimary (citable) accession number: Q9P2J5
Secondary accession number(s): A2RRR4
, A7E266, B4DJ10, Q2TU79, Q9NSE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 30, 2016
This is version 145 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.