LEU1_YEAST
ID LEU1_YEAST Reviewed; 619 AA.
AC P06208; D6W175;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=2-isopropylmalate synthase;
DE EC=2.3.3.13 {ECO:0000269|PubMed:3275644};
DE AltName: Full=Alpha-IPM synthase;
DE AltName: Full=Alpha-isopropylmalate synthase;
GN Name=LEU4; OrderedLocusNames=YNL104C; ORFNames=N2173;
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=2420798; DOI=10.1016/s0021-9258(19)89228-1;
RA Beltzer J.P., Chang L.-F.L., Hinkkanen A.E., Kohlhaw G.B.;
RT "Structure of yeast LEU4. The 5' flanking region contains features that
RT predict two modes of control and two productive translation starts.";
RL J. Biol. Chem. 261:5160-5167(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8701612;
RX DOI=10.1002/(sici)1097-0061(19960330)12:4<403::aid-yea923>3.0.co;2-h;
RA Saiz J.E., Buitrago M.J., Soler A., del Rey F., Revuelta J.L.;
RT "The sequence of a 21.3 kb DNA fragment from the left arm of yeast
RT chromosome XIV reveals LEU4, MET4, POL1, RAS2, and six new open reading
RT frames.";
RL Yeast 12:403-409(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8446029; DOI=10.1111/j.1365-2958.1993.tb01113.x;
RA Mountain H.A., Bystroem A.S., Korch C.;
RT "The general amino acid control regulates MET4, which encodes a methionine-
RT pathway-specific transcriptional activator of Saccharomyces cerevisiae.";
RL Mol. Microbiol. 7:215-228(1993).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ALTERNATIVE INITIATION.
RX PubMed=3275644; DOI=10.1016/s0021-9258(19)57402-6;
RA Beltzer J.P., Morris S.R., Kohlhaw G.B.;
RT "Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-
RT isopropylmalate synthase.";
RL J. Biol. Chem. 263:368-374(1988).
RN [7]
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).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA
CC with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-
CC hydroxy-4-methylpentanoate (2-isopropylmalate).
CC {ECO:0000269|PubMed:3275644}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-
CC isopropylmalate + CoA + H(+); Xref=Rhea:RHEA:21524, ChEBI:CHEBI:1178,
CC ChEBI:CHEBI:11851, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.13;
CC Evidence={ECO:0000269|PubMed:3275644};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21525;
CC Evidence={ECO:0000269|PubMed:3275644};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000305|PubMed:3275644}.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P06208; Q12166: LEU9; NbExp=3; IntAct=EBI-10116, EBI-37359;
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC {ECO:0000269|PubMed:3275644}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000269|PubMed:3275644}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial {ECO:0000303|PubMed:3275644};
CC IsoId=P06208-1; Sequence=Displayed;
CC Name=Cytoplasmic {ECO:0000303|PubMed:3275644};
CC IsoId=P06208-2; Sequence=VSP_018640;
CC -!- MISCELLANEOUS: Present with 6630 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. LeuA type 2 subfamily. {ECO:0000305}.
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DR EMBL; M12893; AAA34743.1; -; Genomic_DNA.
DR EMBL; M12893; AAA34744.1; -; Genomic_DNA.
DR EMBL; Z50161; CAA90522.1; -; Genomic_DNA.
DR EMBL; Z71380; CAA95980.1; -; Genomic_DNA.
DR EMBL; Z12126; CAA78110.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10441.1; -; Genomic_DNA.
DR PIR; A23872; A23872.
DR RefSeq; NP_014295.1; NM_001182942.1. [P06208-1]
DR AlphaFoldDB; P06208; -.
DR SMR; P06208; -.
DR BioGRID; 35719; 134.
DR DIP; DIP-1412N; -.
DR IntAct; P06208; 6.
DR MINT; P06208; -.
DR STRING; 4932.YNL104C; -.
DR iPTMnet; P06208; -.
DR MaxQB; P06208; -.
DR PaxDb; P06208; -.
DR PeptideAtlas; P06208; -.
DR PRIDE; P06208; -.
DR EnsemblFungi; YNL104C_mRNA; YNL104C; YNL104C. [P06208-1]
DR GeneID; 855619; -.
DR KEGG; sce:YNL104C; -.
DR SGD; S000005048; LEU4.
DR VEuPathDB; FungiDB:YNL104C; -.
DR eggNOG; KOG2367; Eukaryota.
DR GeneTree; ENSGT00940000176815; -.
DR HOGENOM; CLU_004588_3_0_1; -.
DR InParanoid; P06208; -.
DR OMA; FGQGERT; -.
DR BioCyc; YEAST:YNL104C-MON; -.
DR UniPathway; UPA00048; UER00070.
DR PRO; PR:P06208; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P06208; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0003852; F:2-isopropylmalate synthase activity; IDA:SGD.
DR GO; GO:0009098; P:leucine biosynthetic process; IMP:SGD.
DR CDD; cd07942; DRE_TIM_LeuA; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.30.160.270; -; 1.
DR HAMAP; MF_00572; LeuA_type2; 1.
DR InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005668; IPM_Synthase.
DR InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR InterPro; IPR039371; LeuA_N_DRE-TIM.
DR InterPro; IPR000891; PYR_CT.
DR Pfam; PF00682; HMGL-like; 1.
DR Pfam; PF08502; LeuA_dimer; 1.
DR SMART; SM00917; LeuA_dimer; 1.
DR SUPFAM; SSF110921; SSF110921; 1.
DR TIGRFAMs; TIGR00970; leuA_yeast; 1.
DR PROSITE; PS00815; AIPM_HOMOCIT_SYNTH_1; 1.
DR PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Cytoplasm; Leucine biosynthesis;
KW Mitochondrion; Reference proteome; Transferase.
FT CHAIN 1..619
FT /note="2-isopropylmalate synthase"
FT /id="PRO_0000001046"
FT DOMAIN 61..336
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000305"
FT /id="VSP_018640"
SQ SEQUENCE 619 AA; 68409 MW; 6886E76C5DD89CE2 CRC64;
MVKESIIALA EHAASRASRV IPPVKLAYKN MLKDPSSKYK PFNAPKLSNR KWPDNRITRA
PRWLSTDLRD GNQSLPDPMS VEQKKEYFHK LVNIGFKEIE VSFPSASQTD FDFTRYAVEN
APDDVSIQCL VQSREHLIKR TVEALTGAKK ATIHTYLATS DMFREIVFNM SREEAISKAV
EATKLVRKLT KDDPSQQATR WSYEFSPECF SDTPGEFAVE ICEAVKKAWE PTEENPIIFN
LPATVEVASP NVYADQIEYF ATHITEREKV CISTHCHNDR GCGVAATELG MLAGADRVEG
CLFGNGERTG NVDLVTVAMN MYTQGVSPNL DFSDLTSVLD VVERCNKIPV SQRAPYGGDL
VVCAFSGSHQ DAIKKGFNLQ NKKRAQGETQ WRIPYLPLDP KDIGRDYEAV IRVNSQSGKG
GAAWVILRSL GLDLPRNMQI EFSSAVQDHA DSLGRELKSD EISKLFKEAY NYNDEQYQAI
SLVNYNVEKF GTERRVFTGQ VKVGDQIVDI EGTGNGPISS LVDALSNLLN VRFAVANYTE
HSLGSGSSTQ AASYIHLSYR RNADNEKAYK WGVGVSEDVG DSSVRAIFAT INNIIHSGDV
SIPSLAEVEG KNAAASGSA
