Full text data of LARS
LARS
(KIAA1352)
[Confidence: low (only semi-automatic identification from reviews)]
Leucine--tRNA ligase, cytoplasmic; 6.1.1.4 (Leucyl-tRNA synthetase; LeuRS)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Leucine--tRNA ligase, cytoplasmic; 6.1.1.4 (Leucyl-tRNA synthetase; LeuRS)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9P2J5
ID SYLC_HUMAN Reviewed; 1176 AA.
AC Q9P2J5; A7E266; Q9NSE1;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2004, sequence version 2.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Leucine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.4;
DE AltName: Full=Leucyl-tRNA synthetase;
DE Short=LeuRS;
GN Name=LARS; Synonyms=KIAA1352;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-1088.
RC TISSUE=Brain;
RA Motegi H., Noda T., Shiba K.;
RT "Cloning and sequence determination of a human cytoplasmic leucyl-tRNA
RT synthetase gene.";
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 260-509 IN COMPLEX WITH
RP (6-(ETHYLAMINO)-5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL) AND AMP, AND
RP FUNCTION.
RX PubMed=19426743; DOI=10.1016/j.jmb.2009.04.073;
RA Seiradake E., Mao W., Hernandez V., Baker S.J., Plattner J.J.,
RA Alley M.R.K., Cusack S.;
RT "Crystal structures of the human and fungal cytosolic Leucyl-tRNA
RT synthetase editing domains: A structural basis for the rational design
RT of antifungal benzoxaboroles.";
RL J. Mol. Biol. 390:196-207(2009).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to
CC its cognate tRNA in a two step reaction: the amino acid (AA) is
CC first activated by ATP to form AA-AMP and then transferred to the
CC acceptor end of the tRNA. Exhibits a post-transfer editing
CC activity to hydrolyze mischarged tRNAs.
CC -!- CATALYTIC ACTIVITY: ATP + L-leucine + tRNA(Leu) = AMP +
CC diphosphate + L-leucyl-tRNA(Leu).
CC -!- ENZYME REGULATION: (5-fluoro-1,3-dihydro-1-hydroxy-1,2-
CC benzoxaborole) inhibits LARS by forming a covalent adduct with the
CC 3' adenosine of tRNA(Leu) at the editing site, thus locking the
CC enzyme in an inactive conformation.
CC -!- INTERACTION:
CC P54136:RARS; NbExp=3; IntAct=EBI-356077, EBI-355482;
CC Q8N122:RPTOR; NbExp=3; IntAct=EBI-356077, EBI-1567928;
CC Q9NQL2:RRAGD; NbExp=13; IntAct=EBI-356077, EBI-992949;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92590.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D84223; BAA95667.1; -; mRNA.
DR EMBL; AB037773; BAA92590.1; ALT_INIT; mRNA.
DR EMBL; CH471062; EAW61848.1; -; Genomic_DNA.
DR EMBL; BC150213; AAI50214.1; -; mRNA.
DR EMBL; BC151214; AAI51215.1; -; mRNA.
DR EMBL; BC152422; AAI52423.1; -; mRNA.
DR RefSeq; NP_064502.9; NM_020117.9.
DR UniGene; Hs.432674; -.
DR PDB; 2WFD; X-ray; 3.25 A; A/B=260-509.
DR PDBsum; 2WFD; -.
DR ProteinModelPortal; Q9P2J5; -.
DR SMR; Q9P2J5; 13-910.
DR IntAct; Q9P2J5; 14.
DR MINT; MINT-1158952; -.
DR STRING; 9606.ENSP00000377954; -.
DR BindingDB; Q9P2J5; -.
DR ChEMBL; CHEMBL3258; -.
DR DrugBank; DB00149; L-Leucine.
DR PhosphoSite; Q9P2J5; -.
DR DMDM; 48428689; -.
DR PaxDb; Q9P2J5; -.
DR PeptideAtlas; Q9P2J5; -.
DR PRIDE; Q9P2J5; -.
DR Ensembl; ENST00000394434; ENSP00000377954; ENSG00000133706.
DR GeneID; 51520; -.
DR KEGG; hsa:51520; -.
DR UCSC; uc003lnx.1; human.
DR CTD; 51520; -.
DR GeneCards; GC05M145473; -.
DR HGNC; HGNC:6512; LARS.
DR HPA; HPA036424; -.
DR MIM; 151350; gene.
DR neXtProt; NX_Q9P2J5; -.
DR PharmGKB; PA30297; -.
DR eggNOG; COG0495; -.
DR HOGENOM; HOG000216621; -.
DR HOVERGEN; HBG055325; -.
DR InParanoid; Q9P2J5; -.
DR KO; K01869; -.
DR OMA; GFYEGVM; -.
DR OrthoDB; EOG7VB2DJ; -.
DR PhylomeDB; Q9P2J5; -.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; LARS; human.
DR EvolutionaryTrace; Q9P2J5; -.
DR GeneWiki; Leucyl-tRNA_synthetase; -.
DR GenomeRNAi; 51520; -.
DR NextBio; 55220; -.
DR PRO; PR:Q9P2J5; -.
DR ArrayExpress; Q9P2J5; -.
DR Bgee; Q9P2J5; -.
DR CleanEx; HS_LARS; -.
DR Genevestigator; Q9P2J5; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004823; F:leucine-tRNA ligase activity; TAS:Reactome.
DR GO; GO:0006429; P:leucyl-tRNA aminoacylation; IEA:InterPro.
DR GO; GO:0006450; P:regulation of translational fidelity; IEA:GOC.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 3.40.50.620; -; 3.
DR Gene3D; 3.90.740.10; -; 1.
DR InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR InterPro; IPR002300; aa-tRNA-synth_Ia.
DR InterPro; IPR004493; Leu-tRNA-synth_Ia_arc/euk.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009080; tRNAsynth_1a_anticodon-bd.
DR InterPro; IPR013155; V/L/I-tRNA-synth_anticodon-bd.
DR InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR Pfam; PF08264; Anticodon_1; 1.
DR Pfam; PF00133; tRNA-synt_1; 2.
DR SUPFAM; SSF47323; SSF47323; 1.
DR SUPFAM; SSF50677; SSF50677; 2.
DR TIGRFAMs; TIGR00395; leuS_arch; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminoacyl-tRNA synthetase; ATP-binding;
KW Complete proteome; Cytoplasm; Ligase; Nucleotide-binding;
KW Polymorphism; Protein biosynthesis; Reference proteome.
FT CHAIN 1 1176 Leucine--tRNA ligase, cytoplasmic.
FT /FTId=PRO_0000152150.
FT REGION 260 509 Editing domain.
FT MOTIF 53 63 "HIGH" region.
FT MOTIF 716 720 "KMSKS" region.
FT BINDING 719 719 ATP (By similarity).
FT VARIANT 1088 1088 R -> K (in dbSNP:rs10988).
FT /FTId=VAR_052637.
FT CONFLICT 271 271 V -> A (in Ref. 1; BAA95667).
FT CONFLICT 892 892 N -> D (in Ref. 1; BAA95667).
FT STRAND 263 274
FT HELIX 277 282
FT STRAND 287 294
FT HELIX 296 301
FT STRAND 304 307
FT STRAND 309 311
FT STRAND 314 317
FT STRAND 323 326
FT HELIX 328 335
FT TURN 336 338
FT STRAND 339 342
FT STRAND 348 351
FT HELIX 354 357
FT STRAND 361 363
FT STRAND 368 370
FT STRAND 372 376
FT STRAND 382 385
FT STRAND 387 391
FT TURN 393 395
FT HELIX 397 408
FT HELIX 411 414
FT TURN 415 417
FT HELIX 420 422
FT TURN 423 425
FT STRAND 432 434
FT TURN 435 437
FT STRAND 438 440
FT HELIX 441 448
FT HELIX 457 474
FT HELIX 487 500
FT STRAND 503 508
SQ SEQUENCE 1176 AA; 134466 MW; 44A4D1A1EF31634A CRC64;
MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF PYPYMNGRLH
LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE
EEEEEETSVK TEDIIIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW
LDYFPPLAIQ DLKRMGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY
SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF
GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK ELMGEEILGA
SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI AALRDLKKKQ ALRAKYGIRD
DMVLPFEPVP VIEIPGFGNL SAVTICDELK IQSQNDREKL AEAKEKIYLK GFYEGIMLVD
GFKGQKVQDV KKTIQKKMID AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK
KQTSQCLKNL ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY
MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI AKEKLDQLKQ
EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW PTAVRANGHL LLNSEKMSKS
TGNFLTLTQA IDKFSADGMR LALADAGDTV EDANFVEAMA DAGILRLYTW VEWVKEMVAN
WDSLRSGPAS TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV
EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ
YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE
ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL
MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH
FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP
ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH
//
ID SYLC_HUMAN Reviewed; 1176 AA.
AC Q9P2J5; A7E266; Q9NSE1;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2004, sequence version 2.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Leucine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.4;
DE AltName: Full=Leucyl-tRNA synthetase;
DE Short=LeuRS;
GN Name=LARS; Synonyms=KIAA1352;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-1088.
RC TISSUE=Brain;
RA Motegi H., Noda T., Shiba K.;
RT "Cloning and sequence determination of a human cytoplasmic leucyl-tRNA
RT synthetase gene.";
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 260-509 IN COMPLEX WITH
RP (6-(ETHYLAMINO)-5-FLUOROBENZO[C][1,2]OXABOROL-1(3H)-OL) AND AMP, AND
RP FUNCTION.
RX PubMed=19426743; DOI=10.1016/j.jmb.2009.04.073;
RA Seiradake E., Mao W., Hernandez V., Baker S.J., Plattner J.J.,
RA Alley M.R.K., Cusack S.;
RT "Crystal structures of the human and fungal cytosolic Leucyl-tRNA
RT synthetase editing domains: A structural basis for the rational design
RT of antifungal benzoxaboroles.";
RL J. Mol. Biol. 390:196-207(2009).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to
CC its cognate tRNA in a two step reaction: the amino acid (AA) is
CC first activated by ATP to form AA-AMP and then transferred to the
CC acceptor end of the tRNA. Exhibits a post-transfer editing
CC activity to hydrolyze mischarged tRNAs.
CC -!- CATALYTIC ACTIVITY: ATP + L-leucine + tRNA(Leu) = AMP +
CC diphosphate + L-leucyl-tRNA(Leu).
CC -!- ENZYME REGULATION: (5-fluoro-1,3-dihydro-1-hydroxy-1,2-
CC benzoxaborole) inhibits LARS by forming a covalent adduct with the
CC 3' adenosine of tRNA(Leu) at the editing site, thus locking the
CC enzyme in an inactive conformation.
CC -!- INTERACTION:
CC P54136:RARS; NbExp=3; IntAct=EBI-356077, EBI-355482;
CC Q8N122:RPTOR; NbExp=3; IntAct=EBI-356077, EBI-1567928;
CC Q9NQL2:RRAGD; NbExp=13; IntAct=EBI-356077, EBI-992949;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92590.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D84223; BAA95667.1; -; mRNA.
DR EMBL; AB037773; BAA92590.1; ALT_INIT; mRNA.
DR EMBL; CH471062; EAW61848.1; -; Genomic_DNA.
DR EMBL; BC150213; AAI50214.1; -; mRNA.
DR EMBL; BC151214; AAI51215.1; -; mRNA.
DR EMBL; BC152422; AAI52423.1; -; mRNA.
DR RefSeq; NP_064502.9; NM_020117.9.
DR UniGene; Hs.432674; -.
DR PDB; 2WFD; X-ray; 3.25 A; A/B=260-509.
DR PDBsum; 2WFD; -.
DR ProteinModelPortal; Q9P2J5; -.
DR SMR; Q9P2J5; 13-910.
DR IntAct; Q9P2J5; 14.
DR MINT; MINT-1158952; -.
DR STRING; 9606.ENSP00000377954; -.
DR BindingDB; Q9P2J5; -.
DR ChEMBL; CHEMBL3258; -.
DR DrugBank; DB00149; L-Leucine.
DR PhosphoSite; Q9P2J5; -.
DR DMDM; 48428689; -.
DR PaxDb; Q9P2J5; -.
DR PeptideAtlas; Q9P2J5; -.
DR PRIDE; Q9P2J5; -.
DR Ensembl; ENST00000394434; ENSP00000377954; ENSG00000133706.
DR GeneID; 51520; -.
DR KEGG; hsa:51520; -.
DR UCSC; uc003lnx.1; human.
DR CTD; 51520; -.
DR GeneCards; GC05M145473; -.
DR HGNC; HGNC:6512; LARS.
DR HPA; HPA036424; -.
DR MIM; 151350; gene.
DR neXtProt; NX_Q9P2J5; -.
DR PharmGKB; PA30297; -.
DR eggNOG; COG0495; -.
DR HOGENOM; HOG000216621; -.
DR HOVERGEN; HBG055325; -.
DR InParanoid; Q9P2J5; -.
DR KO; K01869; -.
DR OMA; GFYEGVM; -.
DR OrthoDB; EOG7VB2DJ; -.
DR PhylomeDB; Q9P2J5; -.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; LARS; human.
DR EvolutionaryTrace; Q9P2J5; -.
DR GeneWiki; Leucyl-tRNA_synthetase; -.
DR GenomeRNAi; 51520; -.
DR NextBio; 55220; -.
DR PRO; PR:Q9P2J5; -.
DR ArrayExpress; Q9P2J5; -.
DR Bgee; Q9P2J5; -.
DR CleanEx; HS_LARS; -.
DR Genevestigator; Q9P2J5; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004823; F:leucine-tRNA ligase activity; TAS:Reactome.
DR GO; GO:0006429; P:leucyl-tRNA aminoacylation; IEA:InterPro.
DR GO; GO:0006450; P:regulation of translational fidelity; IEA:GOC.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 3.40.50.620; -; 3.
DR Gene3D; 3.90.740.10; -; 1.
DR InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR InterPro; IPR002300; aa-tRNA-synth_Ia.
DR InterPro; IPR004493; Leu-tRNA-synth_Ia_arc/euk.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009080; tRNAsynth_1a_anticodon-bd.
DR InterPro; IPR013155; V/L/I-tRNA-synth_anticodon-bd.
DR InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR Pfam; PF08264; Anticodon_1; 1.
DR Pfam; PF00133; tRNA-synt_1; 2.
DR SUPFAM; SSF47323; SSF47323; 1.
DR SUPFAM; SSF50677; SSF50677; 2.
DR TIGRFAMs; TIGR00395; leuS_arch; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminoacyl-tRNA synthetase; ATP-binding;
KW Complete proteome; Cytoplasm; Ligase; Nucleotide-binding;
KW Polymorphism; Protein biosynthesis; Reference proteome.
FT CHAIN 1 1176 Leucine--tRNA ligase, cytoplasmic.
FT /FTId=PRO_0000152150.
FT REGION 260 509 Editing domain.
FT MOTIF 53 63 "HIGH" region.
FT MOTIF 716 720 "KMSKS" region.
FT BINDING 719 719 ATP (By similarity).
FT VARIANT 1088 1088 R -> K (in dbSNP:rs10988).
FT /FTId=VAR_052637.
FT CONFLICT 271 271 V -> A (in Ref. 1; BAA95667).
FT CONFLICT 892 892 N -> D (in Ref. 1; BAA95667).
FT STRAND 263 274
FT HELIX 277 282
FT STRAND 287 294
FT HELIX 296 301
FT STRAND 304 307
FT STRAND 309 311
FT STRAND 314 317
FT STRAND 323 326
FT HELIX 328 335
FT TURN 336 338
FT STRAND 339 342
FT STRAND 348 351
FT HELIX 354 357
FT STRAND 361 363
FT STRAND 368 370
FT STRAND 372 376
FT STRAND 382 385
FT STRAND 387 391
FT TURN 393 395
FT HELIX 397 408
FT HELIX 411 414
FT TURN 415 417
FT HELIX 420 422
FT TURN 423 425
FT STRAND 432 434
FT TURN 435 437
FT STRAND 438 440
FT HELIX 441 448
FT HELIX 457 474
FT HELIX 487 500
FT STRAND 503 508
SQ SEQUENCE 1176 AA; 134466 MW; 44A4D1A1EF31634A CRC64;
MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF PYPYMNGRLH
LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE
EEEEEETSVK TEDIIIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW
LDYFPPLAIQ DLKRMGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY
SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF
GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK ELMGEEILGA
SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI AALRDLKKKQ ALRAKYGIRD
DMVLPFEPVP VIEIPGFGNL SAVTICDELK IQSQNDREKL AEAKEKIYLK GFYEGIMLVD
GFKGQKVQDV KKTIQKKMID AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK
KQTSQCLKNL ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY
MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI AKEKLDQLKQ
EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW PTAVRANGHL LLNSEKMSKS
TGNFLTLTQA IDKFSADGMR LALADAGDTV EDANFVEAMA DAGILRLYTW VEWVKEMVAN
WDSLRSGPAS TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV
EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ
YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE
ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL
MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH
FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP
ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH
//
MIM
151350
*RECORD*
*FIELD* NO
151350
*FIELD* TI
*151350 LEUCYL-tRNA SYNTHETASE; LARS
;;LRS;;
LARS1;;
LEUS;;
RNTLS
*FIELD* TX
CLONING
read more
By study of hybrids of Chinese hamster and human cells, Giles et al.
(1980) found evidence that a structural gene for leucyl-tRNA synthetase
is on chromosome 5.
GENE FUNCTION
The aminoacyl-tRNA synthases catalyze ligation of amino acids to their
respective transfer RNAs. Han et al. (2012) showed that LRS senses
intracellular leucine concentration and interacts directly with Rag
GTPase (RRAGD; 608268). RRAGD then activates MTORC1 (601231), a key
regulator of growth. When the authors modified the LRS protein to
inhibit leucine binding, they observed a loss of amino acid regulation
signaling to mTORC1.
MAPPING
Dana and Wasmuth (1982) did cytogenetic and biochemical analyses of
spontaneous segregants from Chinese hamster-human interspecific hybrid
cells that contained human chromosome 5 and expressed the 4 syntenic
genes LEUS, HEXB (606873), EMTB (130620), and CHR (118840), the hybrid
cells being subjected to selective conditions requiring them to retain
the LEUS gene. From these analyses, Dana and Wasmuth (1982) concluded
that the order is as listed above and that the specific locations are:
LEUS, 5pter-5q1; HEXB, 5q13; EMTB, 5q23-5q35; CHR, 5q35. Gerken et al.
(1986) stated that LARS is located in 5cen-q11 and that threonyl-tRNA
synthetase (187790) is closely linked, at 5p13-cen.
NOMENCLATURE
Following the system used for isoenzymes encoded by nuclear genes, in
which 1 is used to designate the cytoplasmic or soluble form and 2 is
used to designate the mitochondrial form (e.g., SOD1 (147450) and SOD2
(147460)), cytoplasmic LARS might be referred to as LARS1, and the
mitochondrial form as LARS2 (604544).
MOLECULAR GENETICS
In a 4-generation family of Irish Travellers segregating infantile liver
failure (615438), Casey et al. (2012) identified homozygosity for 2
missense mutations in the LARS gene. One (Y373C; 151350.0001) was a
mutation at a conserved residue in the connective peptide-1 (CP1)
domain. The other was predicted to be a rare nonpathogenic variant.
*FIELD* AV
.0001
INFANTILE LIVER FAILURE SYNDROME 1 (1 family)
LARS, TYR373CYS
In 6 affected individuals from a consanguineous Irish Traveller family
with infantile syndromic liver failure (615438), Casey et al (2012)
identified homozygosity for an A-to-G transversion at nucleotide 1118
(c.1118A-G) in exon 11 of the LARS gene, leading to a
tyrosine-to-cysteine substitution at codon 373 (Y373C). The Y373C
mutation was predicted to be highly deleterious, was highly conserved
across eukaryotic species (89%), and was not present in 186 control
chromosomes nor had been reported as a common polymorphic variant in
dbSNP or the 1000 Genomes project. All affected individuals were also
homozygous for a second mutation in cis, an A-to-G transition at
nucleotide 245 in exon 4 resulting in a lysine-to-arginine substitution
at codon 82 (K82R; dbSNP rs112954500), which was predicted to be a rare
nonpathogenic variant and was seen in in 2.1 percent (1/48 alleles) of
Irish controls but in no (0/138 alleles) Irish Travellers. All
unaffected individuals of the family were either homozygous wildtype or
heterozygous for the mutations. The Y373C mutation is located within the
editing domain of LARS, known as connective peptide-1 (CP1), and was
predicted to destabilize the protein structure. LARS knockdown achieved
by siRNA in HEK293 cells had no effect on mitochondrial function even
when cells were under physiologic stress.
*FIELD* SA
Giles et al. (1977)
*FIELD* RF
1. 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.: Identification of a mutation in LARS as a novel cause
of infantile hepatopathy. Molec. Genet. Metab. 106: 351-358, 2012.
2. Dana, S.; Wasmuth, J. J.: Selective linkage disruption in human-Chinese
hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and
chr genes on human chromosome 5. Molec. Cell. Biol. 2: 1220-1228,
1982.
3. Gerken, S. C.; Wasmuth, J. J.; Arfin, S. M.: Threonyl-rRNA synthetase
gene maps close to leucyl-tRNA synthetase gene on human chromosome
5. Somat. Cell Molec. Genet. 12: 519-522, 1986.
4. Giles, R. E.; Shimizu, N.; Nichols, E.; Lawrence, J.; Ruddle, F.
H.: Correction of a heat sensitive lesion associated with reduced
leucyl-tRNA activity in Chinese hamster cells by fusion with human
leucocytes. (Abstract) J. Cell Biol. 75: 387A only, 1977.
5. Giles, R. E.; Shimizu, N.; Ruddle, F. H.: Assignment of a human
genetic locus to chromosome 5 which corrects the heat sensitive lesion
associated with reduced leucyl-tRNA synthetase activity in ts025/Cl
Chinese hamster cells. Somat. Cell Genet. 6: 667-687, 1980.
6. Han, J. M.; Jeong, S. J.; Park, M. C.; Kim, G.; Kwon, N. H.; Kim,
H. K.; Ha, S. H.; Ryu, S. H.; Kim, S.: Leucyl-tRNA synthetase is
an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149:
410-424, 2012.
*FIELD* CN
Alan F. Scott - updated: 11/8/2013
Ada Hamosh - updated: 9/27/2013
Victor A. McKusick - updated: 1/13/2000
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 11/11/2013
carol: 11/8/2013
mcolton: 11/8/2013
alopez: 10/21/2013
alopez: 9/27/2013
mgross: 2/21/2000
terry: 1/13/2000
alopez: 8/25/1998
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
marie: 12/15/1986
reenie: 6/25/1986
*RECORD*
*FIELD* NO
151350
*FIELD* TI
*151350 LEUCYL-tRNA SYNTHETASE; LARS
;;LRS;;
LARS1;;
LEUS;;
RNTLS
*FIELD* TX
CLONING
read more
By study of hybrids of Chinese hamster and human cells, Giles et al.
(1980) found evidence that a structural gene for leucyl-tRNA synthetase
is on chromosome 5.
GENE FUNCTION
The aminoacyl-tRNA synthases catalyze ligation of amino acids to their
respective transfer RNAs. Han et al. (2012) showed that LRS senses
intracellular leucine concentration and interacts directly with Rag
GTPase (RRAGD; 608268). RRAGD then activates MTORC1 (601231), a key
regulator of growth. When the authors modified the LRS protein to
inhibit leucine binding, they observed a loss of amino acid regulation
signaling to mTORC1.
MAPPING
Dana and Wasmuth (1982) did cytogenetic and biochemical analyses of
spontaneous segregants from Chinese hamster-human interspecific hybrid
cells that contained human chromosome 5 and expressed the 4 syntenic
genes LEUS, HEXB (606873), EMTB (130620), and CHR (118840), the hybrid
cells being subjected to selective conditions requiring them to retain
the LEUS gene. From these analyses, Dana and Wasmuth (1982) concluded
that the order is as listed above and that the specific locations are:
LEUS, 5pter-5q1; HEXB, 5q13; EMTB, 5q23-5q35; CHR, 5q35. Gerken et al.
(1986) stated that LARS is located in 5cen-q11 and that threonyl-tRNA
synthetase (187790) is closely linked, at 5p13-cen.
NOMENCLATURE
Following the system used for isoenzymes encoded by nuclear genes, in
which 1 is used to designate the cytoplasmic or soluble form and 2 is
used to designate the mitochondrial form (e.g., SOD1 (147450) and SOD2
(147460)), cytoplasmic LARS might be referred to as LARS1, and the
mitochondrial form as LARS2 (604544).
MOLECULAR GENETICS
In a 4-generation family of Irish Travellers segregating infantile liver
failure (615438), Casey et al. (2012) identified homozygosity for 2
missense mutations in the LARS gene. One (Y373C; 151350.0001) was a
mutation at a conserved residue in the connective peptide-1 (CP1)
domain. The other was predicted to be a rare nonpathogenic variant.
*FIELD* AV
.0001
INFANTILE LIVER FAILURE SYNDROME 1 (1 family)
LARS, TYR373CYS
In 6 affected individuals from a consanguineous Irish Traveller family
with infantile syndromic liver failure (615438), Casey et al (2012)
identified homozygosity for an A-to-G transversion at nucleotide 1118
(c.1118A-G) in exon 11 of the LARS gene, leading to a
tyrosine-to-cysteine substitution at codon 373 (Y373C). The Y373C
mutation was predicted to be highly deleterious, was highly conserved
across eukaryotic species (89%), and was not present in 186 control
chromosomes nor had been reported as a common polymorphic variant in
dbSNP or the 1000 Genomes project. All affected individuals were also
homozygous for a second mutation in cis, an A-to-G transition at
nucleotide 245 in exon 4 resulting in a lysine-to-arginine substitution
at codon 82 (K82R; dbSNP rs112954500), which was predicted to be a rare
nonpathogenic variant and was seen in in 2.1 percent (1/48 alleles) of
Irish controls but in no (0/138 alleles) Irish Travellers. All
unaffected individuals of the family were either homozygous wildtype or
heterozygous for the mutations. The Y373C mutation is located within the
editing domain of LARS, known as connective peptide-1 (CP1), and was
predicted to destabilize the protein structure. LARS knockdown achieved
by siRNA in HEK293 cells had no effect on mitochondrial function even
when cells were under physiologic stress.
*FIELD* SA
Giles et al. (1977)
*FIELD* RF
1. 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.: Identification of a mutation in LARS as a novel cause
of infantile hepatopathy. Molec. Genet. Metab. 106: 351-358, 2012.
2. Dana, S.; Wasmuth, J. J.: Selective linkage disruption in human-Chinese
hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and
chr genes on human chromosome 5. Molec. Cell. Biol. 2: 1220-1228,
1982.
3. Gerken, S. C.; Wasmuth, J. J.; Arfin, S. M.: Threonyl-rRNA synthetase
gene maps close to leucyl-tRNA synthetase gene on human chromosome
5. Somat. Cell Molec. Genet. 12: 519-522, 1986.
4. Giles, R. E.; Shimizu, N.; Nichols, E.; Lawrence, J.; Ruddle, F.
H.: Correction of a heat sensitive lesion associated with reduced
leucyl-tRNA activity in Chinese hamster cells by fusion with human
leucocytes. (Abstract) J. Cell Biol. 75: 387A only, 1977.
5. Giles, R. E.; Shimizu, N.; Ruddle, F. H.: Assignment of a human
genetic locus to chromosome 5 which corrects the heat sensitive lesion
associated with reduced leucyl-tRNA synthetase activity in ts025/Cl
Chinese hamster cells. Somat. Cell Genet. 6: 667-687, 1980.
6. Han, J. M.; Jeong, S. J.; Park, M. C.; Kim, G.; Kwon, N. H.; Kim,
H. K.; Ha, S. H.; Ryu, S. H.; Kim, S.: Leucyl-tRNA synthetase is
an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149:
410-424, 2012.
*FIELD* CN
Alan F. Scott - updated: 11/8/2013
Ada Hamosh - updated: 9/27/2013
Victor A. McKusick - updated: 1/13/2000
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 11/11/2013
carol: 11/8/2013
mcolton: 11/8/2013
alopez: 10/21/2013
alopez: 9/27/2013
mgross: 2/21/2000
terry: 1/13/2000
alopez: 8/25/1998
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
marie: 12/15/1986
reenie: 6/25/1986