ID   SYLM_YEAST              Reviewed;         894 AA.
AC   P11325; D6VZ17;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Leucine--tRNA ligase, mitochondrial;
DE            EC=6.1.1.4 {ECO:0000269|PubMed:1990003};
DE   AltName: Full=Leucyl-tRNA synthetase;
DE            Short=LeuRS;
DE   Flags: Precursor;
GN   Name=NAM2; Synonyms=MSL1; OrderedLocusNames=YLR382C; ORFNames=L3502.6;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2826465; DOI=10.1016/s0021-9258(19)35432-8;
RA   Tzagoloff A., Akai A., Kurkulos M., Repetto B.;
RT   "Homology of yeast mitochondrial leucyl-tRNA synthetase and isoleucyl- and
RT   methionyl-tRNA synthetases of Escherichia coli.";
RL   J. Biol. Chem. 263:850-856(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=AB1-4A/8/55;
RX   PubMed=3034607; DOI=10.1002/j.1460-2075.1987.tb04812.x;
RA   Labouesse M., Herbert C.J., Dujardin G., Slonimski P.P.;
RT   "Three suppressor mutations which cure a mitochondrial RNA maturase
RT   deficiency occur at the same codon in the open reading frame of the nuclear
RT   NAM2 gene.";
RL   EMBO J. 6:713-721(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169871;
RA   Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA   Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA   Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA   Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA   Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA   Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA   Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA   Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA   Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA   Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA   Zollner A., Hani J., Hoheisel J.D.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL   Nature 387:87-90(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   PROTEIN SEQUENCE OF 10-31, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, AND SUBCELLULAR LOCATION.
RX   PubMed=1990003; DOI=10.1016/s0021-9258(18)52278-x;
RA   Zagorski W., Castaing B., Herbert C.J., Labouesse M., Martin R.,
RA   Slonimski P.P.;
RT   "Purification and characterization of the Saccharomyces cerevisiae
RT   mitochondrial leucyl-tRNA synthetase.";
RL   J. Biol. Chem. 266:2537-2541(1991).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
CC   -!- FUNCTION: Catalyzes the attachment of leucine to tRNA(Leu) in the
CC       mitochondrion. {ECO:0000269|PubMed:1990003}.
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:0000269|PubMed:1990003};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11689;
CC         Evidence={ECO:0000269|PubMed:1990003};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=7.1 uM for leucine {ECO:0000269|PubMed:1990003};
CC         KM=1.02 uM for tRNA {ECO:0000269|PubMed:1990003};
CC       pH dependence:
CC         Optimum pH is 8.0-9.5. {ECO:0000269|PubMed:1990003};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.
CC         {ECO:0000269|PubMed:1990003};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:1990003}.
CC   -!- MISCELLANEOUS: PubMed:3034607 authors identified this protein as the
CC       gene product of the NAM2 gene, which is capable of compensating for
CC       mutations in mRNA maturase encoded by the fourth intron of the
CC       mitochondrial cytochrome b gene. {ECO:0000305|PubMed:3034607}.
CC   -!- MISCELLANEOUS: Present with 2120 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       {ECO:0000305}.
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DR   EMBL; J03495; AAA34805.1; -; Genomic_DNA.
DR   EMBL; X05143; CAA28791.1; -; Genomic_DNA.
DR   EMBL; U19104; AAB67277.1; -; Genomic_DNA.
DR   EMBL; BK006945; DAA09683.1; -; Genomic_DNA.
DR   PIR; A28521; SYBYLM.
DR   RefSeq; NP_013486.3; NM_001182271.3.
DR   AlphaFoldDB; P11325; -.
DR   SMR; P11325; -.
DR   BioGRID; 31641; 84.
DR   ComplexPortal; CPX-1314; bI4 intron splicing factor complex.
DR   IntAct; P11325; 2.
DR   MINT; P11325; -.
DR   STRING; 4932.YLR382C; -.
DR   MoonProt; P11325; -.
DR   CarbonylDB; P11325; -.
DR   MaxQB; P11325; -.
DR   PaxDb; 4932-YLR382C; -.
DR   PeptideAtlas; P11325; -.
DR   EnsemblFungi; YLR382C_mRNA; YLR382C; YLR382C.
DR   GeneID; 851098; -.
DR   KEGG; sce:YLR382C; -.
DR   AGR; SGD:S000004374; -.
DR   SGD; S000004374; NAM2.
DR   VEuPathDB; FungiDB:YLR382C; -.
DR   eggNOG; KOG0435; Eukaryota.
DR   GeneTree; ENSGT00390000015114; -.
DR   HOGENOM; CLU_004427_2_0_1; -.
DR   InParanoid; P11325; -.
DR   OMA; DDVDWAD; -.
DR   OrthoDB; 2876972at2759; -.
DR   BioCyc; YEAST:G3O-32448-MONOMER; -.
DR   BioGRID-ORCS; 851098; 4 hits in 10 CRISPR screens.
DR   PRO; PR:P11325; -.
DR   Proteomes; UP000002311; Chromosome XII.
DR   RNAct; P11325; Protein.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
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; IDA:SGD.
DR   GO; GO:0097157; F:pre-mRNA intronic binding; IPI:SGD.
DR   GO; GO:0000372; P:Group I intron splicing; IDA:ComplexPortal.
DR   GO; GO:0006429; P:leucyl-tRNA aminoacylation; IDA:SGD.
DR   GO; GO:0032543; P:mitochondrial translation; IGI:SGD.
DR   GO; GO:0006397; P:mRNA processing; IDA:ComplexPortal.
DR   CDD; cd00812; LeuRS_core; 1.
DR   Gene3D; 3.40.50.620; HUPs; 2.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002300; aa-tRNA-synth_Ia.
DR   InterPro; IPR002302; Leu-tRNA-ligase.
DR   InterPro; IPR025709; Leu_tRNA-synth_edit.
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; TIGR00396; leuS_bact; 1.
DR   PANTHER; PTHR43740:SF2; LEUCINE--TRNA LIGASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR43740; LEUCYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   Pfam; PF13603; tRNA-synt_1_2; 1.
DR   PRINTS; PR00985; TRNASYNTHLEU.
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   1: Evidence at protein level;
KW   Aminoacyl-tRNA synthetase; ATP-binding; Direct protein sequencing; Ligase;
KW   Mitochondrion; Nucleotide-binding; Protein biosynthesis;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..9
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:1990003"
FT   CHAIN           10..894
FT                   /note="Leucine--tRNA ligase, mitochondrial"
FT                   /id="PRO_0000035810"
FT   MOTIF           56..66
FT                   /note="'HIGH' region"
FT   MOTIF           646..650
FT                   /note="'KMSKS' region"
FT   BINDING         649
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   894 AA;  101920 MW;  3862CEFFFB10B262 CRC64;
     MLSRPSSRFL STKRGPGPAV KKLIAIGEKW KQKTTRGLPK QDTLNSGSKY ILCQFPYPSG
     ALHIGHLRVY VISDSLNRFY KQKGYNVIHP MGWDAFGLPA ENAAIERSIN PAIWTRDNIA
     KMKQQMQSML ANFDWDREIT TCDPEYYKFT QWIFLKLFEN GLAYRKEAEI NWDPVDMTVL
     ANEQVDAQGR SWRSGAIVEK KQLKQWFLGI TKFAPKLKKH LNQLKDWPSN VKQMQKNWIG
     ESVGAELVFK VADPKFENLI VFTTRPETLF AVQYVALALD HPIVQKYCEE MPDLKEFIQK
     SDQLPNDTKE GFQLPNIKAV NPLTKEEVPI FAAPYVVSSY GSAPSAVMGC PGHDNRDFEF
     WQTNCPGEHI KTCIAPFFDD ASKVTEQERQ RIIDTVPFTS TDGVLTKECG EHSGVLTVVA
     RKSIMGMLNS EGLSKSVVRY KIRDWLISRQ RYWGTPIPII HCDNCGPVPV PESDLPVKLP
     ELEGLDTKGN PLSTIDEFVN VACPSCGSPA KRETDTMDTF IDSSWYYFRF LDPKNTSKPF
     DREIASKNMP VDIYIGGVEH AILHLLYSRF IAKFLGSINA WSDPAGIFEP FKKLVTQGMV
     QGKTYVDPDS GKFLKPDELT FVNDSPDGNT VIIKSNGKVP VVSYEKMSKS KYNGADPNEC
     ILRHGPDATR AHILFQSPIA DALNWDESKI VGIERWLQKV LHLTKNILSL EKDLAISKDY
     KTPTDLNDAE VKFHNDFQRF LKSITESFEV NLSLNTVISD YMKLTNILES ALKKGEVRNE
     MIVQNLQKLV TVIYPAVPSI SEEAAEMINS QMEWNQYRWP EVERTTESKF KKFQIVVNGR
     VKFMYTADKN FLKLGRDAVI ETLMNLPEGR MYLMNKKIKK FVMKFNVISF LFHK
//