ILV3_YEAST
ID ILV3_YEAST Reviewed; 585 AA.
AC P39522; D6VWJ2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Dihydroxy-acid dehydratase, mitochondrial {ECO:0000303|PubMed:8299945};
DE Short=DAD {ECO:0000303|PubMed:8299945};
DE EC=4.2.1.9 {ECO:0000269|PubMed:20008079, ECO:0000269|PubMed:27532773};
DE Flags: Precursor;
GN Name=ILV3 {ECO:0000303|PubMed:8299945}; OrderedLocusNames=YJR016C;
GN ORFNames=J1450;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 82-585, AND FUNCTION.
RC STRAIN=ATCC 26109 / X2180;
RX PubMed=8299945; DOI=10.1016/0378-1119(93)90004-m;
RA Velasco J.A., Cansado J., Pena M.C., Kawakami T., Laborda J., Notario V.;
RT "Cloning of the dihydroxyacid dehydratase-encoding gene (ILV3) from
RT Saccharomyces cerevisiae.";
RL Gene 137:179-185(1993).
RN [4]
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 [5]
RP INDUCTION.
RX PubMed=16041576; DOI=10.1007/s00253-005-0070-2;
RA Schoondermark-Stolk S.A., Jansen M., Veurink J.H., Verkleij A.J.,
RA Verrips C.T., Euverink G.J., Boonstra J., Dijkhuizen L.;
RT "Rapid identification of target genes for 3-methyl-1-butanol production in
RT Saccharomyces cerevisiae.";
RL Appl. Microbiol. Biotechnol. 70:237-246(2006).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DISRUPTION PHENOTYPE,
RP AND SUBCELLULAR LOCATION.
RX PubMed=20008079; DOI=10.1128/ec.00213-09;
RA Ihrig J., Hausmann A., Hain A., Richter N., Hamza I., Lill R.,
RA Muehlenhoff U.;
RT "Iron regulation through the back door: iron-dependent metabolite levels
RT contribute to transcriptional adaptation to iron deprivation in
RT Saccharomyces cerevisiae.";
RL Eukaryot. Cell 9:460-471(2010).
RN [7]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=21798060; DOI=10.1186/1754-6834-4-21;
RA Chen X., Nielsen K.F., Borodina I., Kielland-Brandt M.C., Karhumaa K.;
RT "Increased isobutanol production in Saccharomyces cerevisiae by
RT overexpression of genes in valine metabolism.";
RL Biotechnol. Biofuels 4:21-21(2011).
RN [8]
RP FUNCTION, AND COFACTOR.
RX PubMed=21987576; DOI=10.1074/jbc.m111.296152;
RA Muehlenhoff U., Richter N., Pines O., Pierik A.J., Lill R.;
RT "Specialized function of yeast Isa1 and Isa2 proteins in the maturation of
RT mitochondrial [4Fe-4S] proteins.";
RL J. Biol. Chem. 286:41205-41216(2011).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND BIOTECHNOLOGY.
RX PubMed=22954227; DOI=10.1186/1754-6834-5-65;
RA Brat D., Weber C., Lorenzen W., Bode H.B., Boles E.;
RT "Cytosolic re-localization and optimization of valine synthesis and
RT catabolism enables inseased isobutanol production with the yeast
RT Saccharomyces cerevisiae.";
RL Biotechnol. Biofuels 5:65-65(2012).
RN [10]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=25280745; DOI=10.1007/s00253-014-6081-0;
RA Park S.H., Kim S., Hahn J.S.;
RT "Metabolic engineering of Saccharomyces cerevisiae for the production of
RT isobutanol and 3-methyl-1-butanol.";
RL Appl. Microbiol. Biotechnol. 98:9139-9147(2014).
RN [11]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=26543501; DOI=10.1186/s13068-015-0361-5;
RA Teo W.S., Ling H., Yu A.Q., Chang M.W.;
RT "Metabolic engineering of Saccharomyces cerevisiae for production of fatty
RT acid short- and branched-chain alkyl esters biodiesel.";
RL Biotechnol. Biofuels 8:177-177(2015).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=27532773; DOI=10.7554/elife.15991;
RA Melber A., Na U., Vashisht A., Weiler B.D., Lill R., Wohlschlegel J.A.,
RA Winge D.R.;
RT "Role of Nfu1 and Bol3 in iron-sulfur cluster transfer to mitochondrial
RT clients.";
RL Elife 5:0-0(2016).
RN [13]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=28505306; DOI=10.1093/femsyr/fox029;
RA Generoso W.C., Brinek M., Dietz H., Oreb M., Boles E.;
RT "Secretion of 2,3-dihydroxyisovalerate as a limiting factor for isobutanol
RT production in Saccharomyces cerevisiae.";
RL FEMS Yeast Res. 17:0-0(2017).
RN [14]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=31303893; DOI=10.1186/s13068-019-1486-8;
RA Wess J., Brinek M., Boles E.;
RT "Improving isobutanol production with the yeast Saccharomyces cerevisiae by
RT successively blocking competing metabolic pathways as well as ethanol and
RT glycerol formation.";
RL Biotechnol. Biofuels 12:173-173(2019).
RN [15]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=30850698; DOI=10.1038/s41598-019-40631-5;
RA Park S.H., Hahn J.S.;
RT "Development of an efficient cytosolic isobutanol production pathway in
RT Saccharomyces cerevisiae by optimizing copy numbers and expression of the
RT pathway genes based on the toxic effect of alpha-acetolactate.";
RL Sci. Rep. 9:3996-3996(2019).
RN [16]
RP FUNCTION.
RX PubMed=33620449; DOI=10.1093/femsyr/foab012;
RA Su Y., Shao W., Zhang A., Zhang W.;
RT "Improving isobutanol tolerance and titers through EMS mutagenesis in
RT Saccharomyces cerevisiae.";
RL FEMS Yeast Res. 21:0-0(2021).
CC -!- FUNCTION: Dihydroxyacid dehydratase that catalyzes the third step in
CC the common pathway leading to biosynthesis of branched-chain amino
CC acids (PubMed:20008079, PubMed:21798060, PubMed:21987576,
CC PubMed:22954227, PubMed:25280745, PubMed:26543501, PubMed:27532773,
CC PubMed:28505306, PubMed:31303893, PubMed:30850698, PubMed:33620449,
CC PubMed:8299945). Catalyzes the dehydration of (2R,3R)-2,3-dihydroxy-3-
CC methylpentanoate (2,3-dihydroxy-3-methylvalerate) into 2-oxo-3-
CC methylpentanoate (2-oxo-3-methylvalerate) and of (2R)-2,3-dihydroxy-3-
CC methylbutanoate (2,3-dihydroxyisovalerate) into 2-oxo-3-methylbutanoate
CC (2-oxoisovalerate), the penultimate precursor to L-isoleucine and L-
CC valine, respectively (PubMed:27532773, PubMed:20008079). Required for
CC the synthesis of alpha-isopropylmalate which modulates the activity of
CC LEU3 and subsequently regulates the expression of LEU1
CC (PubMed:20008079). {ECO:0000269|PubMed:20008079,
CC ECO:0000269|PubMed:21798060, ECO:0000269|PubMed:21987576,
CC ECO:0000269|PubMed:22954227, ECO:0000269|PubMed:25280745,
CC ECO:0000269|PubMed:26543501, ECO:0000269|PubMed:27532773,
CC ECO:0000269|PubMed:28505306, ECO:0000269|PubMed:30850698,
CC ECO:0000269|PubMed:31303893, ECO:0000269|PubMed:33620449,
CC ECO:0000305|PubMed:8299945}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate
CC + H2O; Xref=Rhea:RHEA:24809, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:49072; EC=4.2.1.9; Evidence={ECO:0000269|PubMed:20008079,
CC ECO:0000269|PubMed:27532773};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24810;
CC Evidence={ECO:0000305|PubMed:20008079, ECO:0000305|PubMed:27532773};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate = (S)-3-methyl-2-
CC oxopentanoate + H2O; Xref=Rhea:RHEA:27694, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35146, ChEBI:CHEBI:49258; EC=4.2.1.9;
CC Evidence={ECO:0000250|UniProtKB:P05791};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27695;
CC Evidence={ECO:0000250|UniProtKB:P05791};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:21987576, ECO:0000269|PubMed:27532773};
CC Note=Binds 1 [2Fe-2S] cluster per subunit.
CC {ECO:0000269|PubMed:21987576, ECO:0000269|PubMed:27532773};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WKJ5};
CC -!- ACTIVITY REGULATION: Catalytic activity is inactivated under iron-
CC limiting conditions. {ECO:0000269|PubMed:20008079}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 3/4. {ECO:0000305}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 3/4. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:20008079,
CC ECO:0000269|PubMed:22954227}.
CC -!- INDUCTION: Expression is significantly repressed when the pH changes
CC from pH 5.0 to 3.0. {ECO:0000269|PubMed:16041576}.
CC -!- DISRUPTION PHENOTYPE: Strongly reduces the iron responsiveness of
CC expression of LEU1 by affecting the synthesis of alpha-isopropylmalate.
CC {ECO:0000269|PubMed:20008079}.
CC -!- BIOTECHNOLOGY: The branched chain alcohol isobutanol exhibits superior
CC physicochemical properties as an alternative biofuel (PubMed:21798060,
CC PubMed:22954227, PubMed:25280745, PubMed:26543501, PubMed:28505306,
CC PubMed:31303893, PubMed:30850698). Overexpression of isobutanol pathway
CC enzymes such as ILV3 can enhance production of alcohol precursors and
CC are of great interest for biofuel production (PubMed:21798060,
CC PubMed:22954227, PubMed:25280745, PubMed:26543501, PubMed:28505306,
CC PubMed:31303893, PubMed:30850698). {ECO:0000269|PubMed:21798060,
CC ECO:0000269|PubMed:22954227, ECO:0000269|PubMed:25280745,
CC ECO:0000269|PubMed:26543501, ECO:0000269|PubMed:28505306,
CC ECO:0000269|PubMed:30850698, ECO:0000269|PubMed:31303893}.
CC -!- MISCELLANEOUS: Present with 171000 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the IlvD/Edd family. {ECO:0000305}.
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DR EMBL; X87611; CAA60939.1; -; Genomic_DNA.
DR EMBL; Z49516; CAA89540.1; -; Genomic_DNA.
DR EMBL; L13975; AAA34568.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08808.1; -; Genomic_DNA.
DR PIR; S55205; S55205.
DR RefSeq; NP_012550.1; NM_001181674.1.
DR AlphaFoldDB; P39522; -.
DR SMR; P39522; -.
DR BioGRID; 33772; 139.
DR DIP; DIP-6456N; -.
DR IntAct; P39522; 33.
DR MINT; P39522; -.
DR STRING; 4932.YJR016C; -.
DR iPTMnet; P39522; -.
DR MaxQB; P39522; -.
DR PaxDb; P39522; -.
DR PRIDE; P39522; -.
DR TopDownProteomics; P39522; -.
DR EnsemblFungi; YJR016C_mRNA; YJR016C; YJR016C.
DR GeneID; 853473; -.
DR KEGG; sce:YJR016C; -.
DR SGD; S000003777; ILV3.
DR VEuPathDB; FungiDB:YJR016C; -.
DR eggNOG; KOG2448; Eukaryota.
DR HOGENOM; CLU_014271_4_1_1; -.
DR InParanoid; P39522; -.
DR OMA; TQGRNMA; -.
DR BioCyc; YEAST:YJR016C-MON; -.
DR UniPathway; UPA00047; UER00057.
DR UniPathway; UPA00049; UER00061.
DR PRO; PR:P39522; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P39522; protein.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004160; F:dihydroxy-acid dehydratase activity; IMP:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009082; P:branched-chain amino acid biosynthetic process; IMP:SGD.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.30.80; -; 1.
DR HAMAP; MF_00012; IlvD; 1.
DR InterPro; IPR042096; Dihydro-acid_dehy_C.
DR InterPro; IPR004404; DihydroxyA_deHydtase.
DR InterPro; IPR000581; DiOHA_6PGluconate_deHydtase.
DR InterPro; IPR020558; DiOHA_6PGluconate_deHydtase_CS.
DR InterPro; IPR037237; IlvD/EDD_N.
DR Pfam; PF00920; ILVD_EDD; 1.
DR SUPFAM; SSF143975; SSF143975; 1.
DR TIGRFAMs; TIGR00110; ilvD; 1.
DR PROSITE; PS00886; ILVD_EDD_1; 1.
DR PROSITE; PS00887; ILVD_EDD_2; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Iron; Iron-sulfur; Lyase; Magnesium; Metal-binding; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 21..585
FT /note="Dihydroxy-acid dehydratase, mitochondrial"
FT /id="PRO_0000015636"
FT ACT_SITE 500
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 70
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 102
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 143
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 144
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 221
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKJ5"
FT CONFLICT 82..89
FT /note="SQSIEKAG -> MFSIIEKR (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="G -> S (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="P -> S (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="A -> T (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="P -> R (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
FT CONFLICT 551
FT /note="R -> A (in Ref. 3; AAA34568)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 585 AA; 62861 MW; 35AB3C679BA6E8D0 CRC64;
MGLLTKVATS RQFSTTRCVA KKLNKYSYII TEPKGQGASQ AMLYATGFKK EDFKKPQVGV
GSCWWSGNPC NMHLLDLNNR CSQSIEKAGL KAMQFNTIGV SDGISMGTKG MRYSLQSREI
IADSFETIMM AQHYDANIAI PSCDKNMPGV MMAMGRHNRP SIMVYGGTIL PGHPTCGSSK
ISKNIDIVSA FQSYGEYISK QFTEEEREDV VEHACPGPGS CGGMYTANTM ASAAEVLGLT
IPNSSSFPAV SKEKLAECDN IGEYIKKTME LGILPRDILT KEAFENAITY VVATGGSTNA
VLHLVAVAHS AGVKLSPDDF QRISDTTPLI GDFKPSGKYV MADLINVGGT QSVIKYLYEN
NMLHGNTMTV TGDTLAERAK KAPSLPEGQE IIKPLSHPIK ANGHLQILYG SLAPGGAVGK
ITGKEGTYFK GRARVFEEEG AFIEALERGE IKKGEKTVVV IRYEGPRGAP GMPEMLKPSS
ALMGYGLGKD VALLTDGRFS GGSHGFLIGH IVPEAAEGGP IGLVRDGDEI IIDADNNKID
LLVSDKEMAQ RKQSWVAPPP RYTRGTLSKY AKLVSNASNG CVLDA
