SYLC_MOUSE
ID SYLC_MOUSE Reviewed; 1178 AA.
AC Q8BMJ2; Q8BKW9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Leucine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.4;
DE AltName: Full=Leucyl-tRNA synthetase;
DE Short=LeuRS;
GN Name=Lars1; Synonyms=Lars;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-972 AND LYS-1049, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to its
CC cognate tRNA in a two step reaction: the amino acid (AA) is first
CC activated by ATP to form AA-AMP and then transferred to the acceptor
CC end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze
CC mischarged tRNAs. {ECO:0000250|UniProtKB:Q9P2J5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-
CC tRNA(Leu); Xref=Rhea:RHEA:11688, Rhea:RHEA-COMP:9613, Rhea:RHEA-
CC COMP:9622, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78494, ChEBI:CHEBI:456215; EC=6.1.1.4;
CC -!- ACTIVITY REGULATION: 5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole
CC inhibits LARS1 by forming a covalent adduct with the 3' adenosine of
CC tRNA(Leu) at the editing site, thus locking the enzyme in an inactive
CC conformation. {ECO:0000250|UniProtKB:Q9P2J5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
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DR EMBL; AK030778; BAC27133.1; -; mRNA.
DR EMBL; AK049472; BAC33766.1; -; mRNA.
DR CCDS; CCDS37796.1; -.
DR RefSeq; NP_598898.2; NM_134137.2.
DR AlphaFoldDB; Q8BMJ2; -.
DR SMR; Q8BMJ2; -.
DR BioGRID; 223191; 32.
DR IntAct; Q8BMJ2; 2.
DR STRING; 10090.ENSMUSP00000095197; -.
DR iPTMnet; Q8BMJ2; -.
DR PhosphoSitePlus; Q8BMJ2; -.
DR SwissPalm; Q8BMJ2; -.
DR EPD; Q8BMJ2; -.
DR jPOST; Q8BMJ2; -.
DR MaxQB; Q8BMJ2; -.
DR PaxDb; Q8BMJ2; -.
DR PRIDE; Q8BMJ2; -.
DR ProteomicsDB; 253439; -.
DR Antibodypedia; 45640; 123 antibodies from 31 providers.
DR DNASU; 107045; -.
DR Ensembl; ENSMUST00000097590; ENSMUSP00000095197; ENSMUSG00000024493.
DR GeneID; 107045; -.
DR KEGG; mmu:107045; -.
DR UCSC; uc008etp.1; mouse.
DR CTD; 107045; -.
DR MGI; MGI:1913808; Lars.
DR VEuPathDB; HostDB:ENSMUSG00000024493; -.
DR eggNOG; KOG0437; Eukaryota.
DR GeneTree; ENSGT00390000012163; -.
DR HOGENOM; CLU_004174_1_0_1; -.
DR InParanoid; Q8BMJ2; -.
DR OMA; AWNMAFQ; -.
DR OrthoDB; 75155at2759; -.
DR PhylomeDB; Q8BMJ2; -.
DR TreeFam; TF105718; -.
DR BioGRID-ORCS; 107045; 32 hits in 111 CRISPR screens.
DR ChiTaRS; Lars; mouse.
DR PRO; PR:Q8BMJ2; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BMJ2; protein.
DR Bgee; ENSMUSG00000024493; Expressed in floor plate of midbrain and 290 other tissues.
DR ExpressionAtlas; Q8BMJ2; baseline and differential.
DR Genevisible; Q8BMJ2; MM.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:CAFA.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0012505; C:endomembrane system; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004819; F:glutamine-tRNA ligase activity; ISO:MGI.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0004823; F:leucine-tRNA ligase activity; IMP:CAFA.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:MGI.
DR GO; GO:0071233; P:cellular response to leucine; ISO:MGI.
DR GO; GO:1990253; P:cellular response to leucine starvation; ISO:MGI.
DR GO; GO:0006425; P:glutaminyl-tRNA aminoacylation; ISO:MGI.
DR GO; GO:0006429; P:leucyl-tRNA aminoacylation; IDA:CAFA.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:MGI.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISO:MGI.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:0008361; P:regulation of cell size; ISO:MGI.
DR Gene3D; 3.40.50.620; -; 1.
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; IPR013155; M/V/L/I-tRNA-synth_anticd-bd.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd.
DR InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR PANTHER; PTHR45794; PTHR45794; 1.
DR Pfam; PF08264; Anticodon_1; 1.
DR Pfam; PF00133; tRNA-synt_1; 2.
DR SUPFAM; SSF47323; SSF47323; 1.
DR SUPFAM; SSF50677; SSF50677; 1.
DR TIGRFAMs; TIGR00395; leuS_arch; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome.
FT CHAIN 1..1178
FT /note="Leucine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000152151"
FT MOTIF 55..65
FT /note="'HIGH' region"
FT MOTIF 718..722
FT /note="'KMSKS' region"
FT BINDING 721
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT MOD_RES 972
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 1049
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 218
FT /note="S -> P (in Ref. 1; BAC33766)"
FT /evidence="ECO:0000305"
FT CONFLICT 869
FT /note="C -> S (in Ref. 1; BAC33766)"
FT /evidence="ECO:0000305"
FT CONFLICT 954
FT /note="L -> Q (in Ref. 1; BAC27133)"
FT /evidence="ECO:0000305"
FT CONFLICT 1127
FT /note="P -> H (in Ref. 1; BAC27133)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1178 AA; 134192 MW; 1186583D5237FFC1 CRC64;
MAGRKGTAKV DFLKEIEKEA QQKWEAEKVF EVSASRLEKQ KQSSKGKYFV TFPYPYMNGR
LHLGHTFSLS KCEFAVGYQR LKGKSCLFPF GLHCTGMPIK ACADKLKREI ELYGCPPDFP
EEEEEEEESS AKPGDIVVRD KAKGKKSKAA AKAGSSKYQW DIMKSLGLSD DDIVKFSEAE
HWLDYFPPLA VQDLKTIGLK VDWRRSFITT DVNPYYDSFV RWQFLTLRER NKIKFGKRYT
IYSPKDGQPC MDHDRQTGEG VGPQEYTLVK LKVLEPYPSK LSGLKGKNIF LVAATLRPET
MFGQTNCWVR PDMKYIGFET ANGDIFICTQ RAARNMSYQG FTKHNGVVPV VKELMGEEIL
GASLSAPLTC YKVVYVLPML TIKEDKGTGV VTSVPSDSPD DLAALRDLKK KQALRTKFGI
RDDMVLPFEP VPVLEIPGIG NLPAVTVCDE LKIQSQNDRE KLAEAKEKLY LRGFYDGVML
VDGFKGQKIQ HVKKTIQKNM IDAGDALIYM EPEKQVMSRS ADECVVALCD QWYLDYGDEN
WKKQTFQCLK NMETFCEESR KNFEASLDWL QEHACSRTYG LGTRLPWDEQ WLIESLSDST
IYMAFYTVAH LLQGGDLNGQ AESPLGIRPQ QMTKDVWDYV FFKDAPFPKT QIPKEKLDQL
KQEFEFWYPV DLRASGKDLI PNHLSYYIYN HVAMWPEQSD KWPVSVRANG HLLLNSEKMS
KSTGNFLTLS QAVDKFSADG MRLALADAGD TVEDANFVEA MADAGILRLY TWVEWVKEML
ASCSSLRSGP ADSFNDRVFA SEMNAGIIKT DQNYEKMMFK EALKTGFFEF QAAKDKYREL
ATEGMHRELV FRFIEVQTIL LTPFCPHLCE HIWTLLGKPD SIMHASWPVA GPVDESLIRS
SQYLMEVAHD LRLRLKNYMM PAKGKKTDKQ PAQRPSHCTI YVAKNYPVWQ HITLTTLRSH
FEANNGKLPD NKVIASELGS LPELKKYMKK VMPFVAMIKE NMEKKGPRVL DLELEFDEQA
VLMENIVYLT NSLELEHIEV KFASEAEDKV REECCPGKPL NVFRTEPGVP VSLVNPQPSS
GHFSTKIDIR QGDSCESIIR RLMKTDRGIK DLSKVKLMRF DDPLLGPRRV PVLGREHSEK
TLISENAVFH VDLVSKKVHL TENGLRTDIG DTMVYLVH
