LEU3_YEAST
ID LEU3_YEAST Reviewed; 364 AA.
AC P04173; D6VQZ6;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 4.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=3-isopropylmalate dehydrogenase;
DE Short=3-IPM-DH;
DE Short=IMDH;
DE EC=1.1.1.85;
DE AltName: Full=Beta-IPM dehydrogenase;
GN Name=LEU2; OrderedLocusNames=YCL018W; ORFNames=YCL18W;
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=3010239; DOI=10.1093/nar/14.8.3475;
RA Warmington J.R., Anwar R., Newlon C.S., Waring R.B., Davies R.W.,
RA Indge K.J., Oliver S.G.;
RT "A 'hot-spot' for Ty transposition on the left arm of yeast chromosome
RT III.";
RL Nucleic Acids Res. 14:3475-3485(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 38626 / AH22 / NRRL Y-12843;
RX PubMed=6330094; DOI=10.1016/s0021-9258(17)39688-6;
RA Andreadis A., Hsu Y.-P., Hermodson M., Kohlhaw G., Schimmel P.;
RT "Yeast LEU2. Repression of mRNA levels by leucine and primary structure of
RT the gene product.";
RL J. Biol. Chem. 259:8059-8062(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lu Q.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1574125; DOI=10.1038/357038a0;
RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA Sgouros J.G.;
RT "The complete DNA sequence of yeast chromosome III.";
RL Nature 357:38-46(1992).
RN [5]
RP SEQUENCE REVISION TO 69.
RA Valles G., Volckaerts G.;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 213-364.
RX PubMed=6396161; DOI=10.1016/0378-1119(84)90218-x;
RA Froman B.E., Tait R.C., Rodriguez R.L.;
RT "Nucleotide sequence of the 3' terminal region of the LEU2 gene from
RT Saccharomyces cerevisiae.";
RL Gene 31:257-261(1984).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
CC -!- FUNCTION: Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-
CC methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-
CC oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate
CC + CO2 + NADH; Xref=Rhea:RHEA:32271, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17865, ChEBI:CHEBI:35121, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.85;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; X03840; CAA27459.1; -; Genomic_DNA.
DR EMBL; X59720; CAA42366.2; -; Genomic_DNA.
DR EMBL; M12909; AAA66917.1; -; Genomic_DNA.
DR EMBL; BK006937; DAA07465.1; -; Genomic_DNA.
DR PIR; S19344; DEBYI.
DR RefSeq; NP_009911.2; NM_001178665.1.
DR AlphaFoldDB; P04173; -.
DR SMR; P04173; -.
DR BioGRID; 30966; 22.
DR DIP; DIP-7880N; -.
DR IntAct; P04173; 157.
DR MINT; P04173; -.
DR STRING; 4932.YCL018W; -.
DR iPTMnet; P04173; -.
DR SWISS-2DPAGE; P04173; -.
DR PaxDb; P04173; -.
DR PRIDE; P04173; -.
DR EnsemblFungi; YCL018W_mRNA; YCL018W; YCL018W.
DR GeneID; 850342; -.
DR KEGG; sce:YCL018W; -.
DR SGD; S000000523; LEU2.
DR VEuPathDB; FungiDB:YCL018W; -.
DR eggNOG; KOG0786; Eukaryota.
DR GeneTree; ENSGT00950000182989; -.
DR HOGENOM; CLU_031953_0_3_1; -.
DR InParanoid; P04173; -.
DR OMA; EYDLGAR; -.
DR BioCyc; MetaCyc:YCL018W-MON; -.
DR BioCyc; YEAST:YCL018W-MON; -.
DR UniPathway; UPA00048; UER00072.
DR PHI-base; PHI:504; -.
DR PRO; PR:P04173; -.
DR Proteomes; UP000002311; Chromosome III.
DR RNAct; P04173; protein.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IDA:SGD.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0006097; P:glyoxylate cycle; IMP:SGD.
DR GO; GO:0009098; P:leucine biosynthetic process; IMP:SGD.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR004429; Isopropylmalate_DH.
DR PANTHER; PTHR42979; PTHR42979; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00169; leuB; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Cytoplasm;
KW Leucine biosynthesis; Magnesium; Manganese; Metal-binding; NAD;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..364
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083623"
FT BINDING 79..90
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 250
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 254
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 289..300
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 143
FT /note="Important for catalysis"
FT /evidence="ECO:0000250"
FT SITE 192
FT /note="Important for catalysis"
FT /evidence="ECO:0000250"
FT CONFLICT 69
FT /note="A -> V (in Ref. 1, 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="N -> D (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 364 AA; 38953 MW; 4F312E81D829E2A3 CRC64;
MSAPKKIVVL PGDHVGQEIT AEAIKVLKAI SDVRSNVKFD FENHLIGGAA IDATGVPLPD
EALEASKKAD AVLLGAVGGP KWGTGSVRPE QGLLKIRKEL QLYANLRPCN FASDSLLDLS
PIKPQFAKGT DFVVVRELVG GIYFGKRKED DGDGVAWDSE QYTVPEVQRI TRMAAFMALQ
HEPPLPIWSL DKANVLASSR LWRKTVEETI KNEFPTLKVQ HQLIDSAAMI LVKNPTHLNG
IIITSNMFGD IISDEASVIP GSLGLLPSAS LASLPDKNTA FGLYEPCHGS APDLPKNKVN
PIATILSAAM MLKLSLNLPE EGKAIEDAVK KVLDAGIRTG DLGGSNSTTE VGDAVAEEVK
KILA
