ID   SYLC_PONAB              Reviewed;        1176 AA.
AC   Q5R614;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   24-JAN-2024, entry version 88.
DE   RecName: Full=Leucine--tRNA ligase, cytoplasmic {ECO:0000250|UniProtKB:Q9P2J5};
DE            EC=6.1.1.4 {ECO:0000250|UniProtKB:Q9P2J5};
DE   AltName: Full=Leucyl-tRNA synthetase {ECO:0000250|UniProtKB:Q9P2J5};
DE            Short=LeuRS {ECO:0000250|UniProtKB:Q9P2J5};
GN   Name=LARS1; Synonyms=LARS;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Aminoacyl-tRNA synthetase that catalyzes the specific
CC       attachment of leucine to its cognate tRNA (tRNA(Leu)). It performs tRNA
CC       aminoacylation in a two-step reaction: Leu is initially activated by
CC       ATP to form a leucyl-adenylate (Leu-AMP) intermediate; then the leucyl
CC       moiety is transferred to the acceptor 3' end of the tRNA to yield
CC       leucyl-tRNA. To improve the fidelity of catalytic reactions, it is also
CC       able to hydrolyze misactivated aminoacyl-adenylate intermediates (pre-
CC       transfer editing) and mischarged aminoacyl-tRNAs (post-transfer
CC       editing). {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         Evidence={ECO:0000250|UniProtKB:Q9P2J5};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11689;
CC         Evidence={ECO:0000250|UniProtKB:Q9P2J5};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-methionyl-tRNA(Leu) = H(+) + L-methionine + tRNA(Leu);
CC         Xref=Rhea:RHEA:77535, Rhea:RHEA-COMP:9613, Rhea:RHEA-COMP:18931,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57844,
CC         ChEBI:CHEBI:78442, ChEBI:CHEBI:78530;
CC         Evidence={ECO:0000250|UniProtKB:Q9P2J5};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77536;
CC         Evidence={ECO:0000250|UniProtKB:Q9P2J5};
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   -!- DOMAIN: The structure of cytoplasmic leucine-tRNA ligase includes four
CC       main functional domains: the Rossmann-fold aminoacylation domain, the
CC       editing domain known as connective peptide 1 (CP1), the anticodon
CC       binding domain for tRNA recognition, and the vertebrate C-terminal (VC)
CC       domain for tRNA binding. {ECO:0000250|UniProtKB:Q9P2J5}.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       {ECO:0000305}.
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DR   EMBL; CR860686; CAH92802.1; -; mRNA.
DR   AlphaFoldDB; Q5R614; -.
DR   SMR; Q5R614; -.
DR   STRING; 9601.ENSPPYP00000017795; -.
DR   eggNOG; KOG0437; Eukaryota.
DR   InParanoid; Q5R614; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0002161; F:aminoacyl-tRNA editing activity; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004823; F:leucine-tRNA ligase activity; ISS:UniProtKB.
DR   GO; GO:0006429; P:leucyl-tRNA aminoacylation; ISS:UniProtKB.
DR   CDD; cd07959; Anticodon_Ia_Leu_AEc; 1.
DR   Gene3D; 3.40.50.620; HUPs; 1.
DR   Gene3D; 3.90.740.10; Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain; 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   NCBIfam; TIGR00395; leuS_arch; 1.
DR   PANTHER; PTHR45794:SF1; LEUCINE--TRNA LIGASE, CYTOPLASMIC; 1.
DR   PANTHER; PTHR45794; LEUCYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF00133; tRNA-synt_1; 2.
DR   SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF50677; ValRS/IleRS/LeuRS editing domain; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW   Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..1176
FT                   /note="Leucine--tRNA ligase, cytoplasmic"
FT                   /id="PRO_0000229767"
FT   REGION          115..142
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          260..509
FT                   /note="Editing domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   MOTIF           60..63
FT                   /note="'HIGH' region"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   MOTIF           716..720
FT                   /note="'KMSKS' region"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   BINDING         52
FT                   /ligand="L-leucine"
FT                   /ligand_id="ChEBI:CHEBI:57427"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   BINDING         54
FT                   /ligand="L-leucine"
FT                   /ligand_id="ChEBI:CHEBI:57427"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   BINDING         594
FT                   /ligand="L-leucine"
FT                   /ligand_id="ChEBI:CHEBI:57427"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   BINDING         597
FT                   /ligand="L-leucine"
FT                   /ligand_id="ChEBI:CHEBI:57427"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   BINDING         719
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   MOD_RES         167
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   MOD_RES         720
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9P2J5"
FT   MOD_RES         970
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMJ2"
FT   MOD_RES         1047
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BMJ2"
SQ   SEQUENCE   1176 AA;  134562 MW;  D9D6C47D90443485 CRC64;
     MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASSLEKQ TSKGKYFVTF PYPYMNGRLH
     LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE
     EDEEEETNVK TEDTRIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW
     LDYFPPLAIQ DLKRLGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY
     SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETLF
     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
     WDSLRSGPAN TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV
     EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VDEVLIHSSQ
     YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE
     ANNRKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL
     MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSIS LVNPQPSNGH
     FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEHTEKTP
     ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH
//