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Protein

Leucine--tRNA ligase, cytoplasmic

Gene

LARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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).

Activity 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

  • aminoacyl-tRNA editing activity Source: InterPro
  • ATP binding Source: UniProtKB-KW
  • glutamine-tRNA ligase activity Source: UniProtKB
  • GTPase activator activity Source: CAFA
  • leucine-tRNA ligase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, Ligase
Biological processProtein biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000133706.17
HGNCiHGNC:6512 LARS
MIMi151350 gene
neXtProtiNX_Q9P2J5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs201861847EnsemblClinVar.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
ProteomicsDBi83822

PTM databases

iPTMnetiQ9P2J5
PhosphoSitePlusiQ9P2J5
SwissPalmiQ9P2J5

Expressioni

Gene expression databases

BgeeiENSG00000133706 Expressed in 225 organ(s), highest expression level in kidney
CleanExiHS_LARS
ExpressionAtlasiQ9P2J5 baseline and differential
GenevisibleiQ9P2J5 HS

Organism-specific databases

HPAiHPA036424
HPA040881

Interactioni

Binary interactionsi

Protein-protein interaction databases

BioGridi119584, 146 interactors
CORUMiQ9P2J5
IntActiQ9P2J5, 32 interactors
MINTiQ9P2J5
STRINGi9606.ENSP00000377954

Chemistry databases

BindingDBiQ9P2J5

Structurei

Secondary structure

11176
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
HOVERGENiHBG075313
InParanoidiQ9P2J5
KOiK01869
OMAiHVTGTPI
OrthoDBiEOG091G01VH
PhylomeDBiQ9P2J5
TreeFamiTF105718

Family and domain databases

InterProiView protein in InterPro
IPR001412 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
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR009008 Val/Leu/Ile-tRNA-synth_edit
PANTHERiPTHR11946:SF51 PTHR11946:SF51, 1 hit
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00133 tRNA-synt_1, 2 hits
SUPFAMiSSF47323 SSF47323, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00395 leuS_arch, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WXY1A0A087WXY1_HUMAN
Leucine--tRNA ligase, cytoplasmic
LARS
160Annotation score:

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 → R1 PublicationCorresponds to variant dbSNP:rs112954500EnsemblClinVar.1
Natural variantiVAR_070438373Y → C in ILFS1. 1 PublicationCorresponds to variant dbSNP:rs201861847EnsemblClinVar.1
Natural variantiVAR_0526371088R → K1 PublicationCorresponds to variant dbSNP:rs10988EnsemblClinVar.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

Similar proteinsi

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, 146 interactors
CORUMiQ9P2J5
IntActiQ9P2J5, 32 interactors
MINTiQ9P2J5
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
ProteomicsDBi83822

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
EuPathDBiHostDB:ENSG00000133706.17
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
HOVERGENiHBG075313
InParanoidiQ9P2J5
KOiK01869
OMAiHVTGTPI
OrthoDBiEOG091G01VH
PhylomeDBiQ9P2J5
TreeFamiTF105718

Enzyme and pathway databases

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
PROiPR:Q9P2J5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133706 Expressed in 225 organ(s), highest expression level in kidney
CleanExiHS_LARS
ExpressionAtlasiQ9P2J5 baseline and differential
GenevisibleiQ9P2J5 HS

Family and domain databases

InterProiView protein in InterPro
IPR001412 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
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR009008 Val/Leu/Ile-tRNA-synth_edit
PANTHERiPTHR11946:SF51 PTHR11946:SF51, 1 hit
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00133 tRNA-synt_1, 2 hits
SUPFAMiSSF47323 SSF47323, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00395 leuS_arch, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSYLC_HUMAN
AccessioniPrimary (citable) accession number: Q9P2J5
Secondary accession number(s): A2RRR4
, A7E266, B4DJ10, Q2TU79, Q9NSE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 7, 2018
This is version 165 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  7. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
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