ID   LEU9_YEAST              Reviewed;         604 AA.
AC   Q12166; D6W2G7;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-NOV-2023, entry version 152.
DE   RecName: Full=2-isopropylmalate synthase 2, mitochondrial;
DE            EC=2.3.3.13;
DE   AltName: Full=Alpha-IPM synthase 2;
DE   AltName: Full=Alpha-isopropylmalate synthase 2;
DE   AltName: Full=Alpha-isopropylmalate synthase II;
DE   Flags: Precursor;
GN   Name=LEU9 {ECO:0000303|PubMed:10790691}; OrderedLocusNames=YOR108W;
GN   ORFNames=YOR3227w;
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=9200815;
RX   DOI=10.1002/(sici)1097-0061(19970615)13:7<655::aid-yea120>3.0.co;2-i;
RA   Voss H., Benes V., Andrade M.A., Valencia A., Rechmann S., Teodoru C.,
RA   Schwager C., Paces V., Sander C., Ansorge W.;
RT   "DNA sequencing and analysis of 130 kb from yeast chromosome XV.";
RL   Yeast 13:655-672(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [3]
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   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=10790691;
RX   DOI=10.1002/(sici)1097-0061(200004)16:6<539::aid-yea547>3.0.co;2-k;
RA   Casalone E., Barberio C., Cavalieri D., Polsinelli M.;
RT   "Identification by functional analysis of the gene encoding alpha-
RT   isopropylmalate synthase II (LEU9) in Saccharomyces cerevisiae.";
RL   Yeast 16:539-545(2000).
RN   [5]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
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).
RN   [7]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=16823961; DOI=10.1021/pr050477f;
RA   Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT   "Toward the complete yeast mitochondrial proteome: multidimensional
RT   separation techniques for mitochondrial proteomics.";
RL   J. Proteome Res. 5:1543-1554(2006).
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). Redundant to LEU4,
CC       responsible for about 20% of alpha-IPMS activity. Involved in leucine
CC       synthesis. {ECO:0000269|PubMed:10790691}.
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   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000250|UniProtKB:P9WQB3,
CC         ECO:0000250|UniProtKB:Q9JZG1};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P9WQB3}.
CC   -!- INTERACTION:
CC       Q12166; P06208: LEU4; NbExp=3; IntAct=EBI-37359, EBI-10116;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095,
CC       ECO:0000269|PubMed:16823961}.
CC   -!- DISRUPTION PHENOTYPE: Retains 79% 2-isopropylmalate synthase activity
CC       and grows in the absence of Leu; a double LEU1-LEU9 deletion has no 2-
CC       isopropylmalate synthase, does not grow in the absence of Leu.
CC       {ECO:0000269|PubMed:10790691}.
CC   -!- MISCELLANEOUS: Present with 28800 molecules/cell in log phase SD
CC       medium. {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; X94335; CAA64028.1; -; Genomic_DNA.
DR   EMBL; Z75016; CAA99306.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA10883.1; -; Genomic_DNA.
DR   PIR; S66993; S66993.
DR   RefSeq; NP_014751.1; NM_001183527.1.
DR   AlphaFoldDB; Q12166; -.
DR   SMR; Q12166; -.
DR   BioGRID; 34504; 73.
DR   DIP; DIP-4153N; -.
DR   IntAct; Q12166; 5.
DR   MINT; Q12166; -.
DR   STRING; 4932.YOR108W; -.
DR   iPTMnet; Q12166; -.
DR   MaxQB; Q12166; -.
DR   PaxDb; 4932-YOR108W; -.
DR   PeptideAtlas; Q12166; -.
DR   EnsemblFungi; YOR108W_mRNA; YOR108W; YOR108W.
DR   GeneID; 854275; -.
DR   KEGG; sce:YOR108W; -.
DR   AGR; SGD:S000005634; -.
DR   SGD; S000005634; LEU9.
DR   VEuPathDB; FungiDB:YOR108W; -.
DR   eggNOG; KOG2367; Eukaryota.
DR   GeneTree; ENSGT00940000176815; -.
DR   HOGENOM; CLU_004588_3_0_1; -.
DR   InParanoid; Q12166; -.
DR   OMA; WPDKVID; -.
DR   OrthoDB; 275559at2759; -.
DR   BioCyc; YEAST:MONOMER3O-59; -.
DR   UniPathway; UPA00048; UER00070.
DR   BioGRID-ORCS; 854275; 0 hits in 10 CRISPR screens.
DR   PRO; PR:Q12166; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; Q12166; Protein.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IDA:SGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0009098; P:leucine biosynthetic process; IMP:SGD.
DR   CDD; cd07942; DRE_TIM_LeuA; 1.
DR   Gene3D; 3.30.160.270; -; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 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   NCBIfam; TIGR00970; leuA_yeast; 1.
DR   PANTHER; PTHR46911; -; 1.
DR   PANTHER; PTHR46911:SF2; 2-ISOPROPYLMALATE SYNTHASE-RELATED; 1.
DR   Pfam; PF00682; HMGL-like; 1.
DR   Pfam; PF08502; LeuA_dimer; 1.
DR   SMART; SM00917; LeuA_dimer; 1.
DR   SUPFAM; SSF110921; 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain; 1.
DR   SUPFAM; SSF51569; Aldolase; 1.
DR   SUPFAM; SSF89000; post-HMGL domain-like; 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   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW   Leucine biosynthesis; Metal-binding; Mitochondrion; Reference proteome;
KW   Transferase; Transit peptide.
FT   TRANSIT         1..50
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           51..604
FT                   /note="2-isopropylmalate synthase 2, mitochondrial"
FT                   /id="PRO_0000255958"
FT   DOMAIN          60..335
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT   BINDING         69
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P9WQB3"
FT   BINDING         274
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P9WQB3"
FT   BINDING         276
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P9WQB3"
FT   BINDING         310
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P9WQB3"
SQ   SEQUENCE   604 AA;  67200 MW;  0E5B049FFBB6097E CRC64;
     MVKHSFIALA EHASKLRRSI PPVKLTYKNM LRDPSVKYRA FAPPKMVKRI WPDKTIQKAP
     RWLSTDLRDG NQSLPDPMSV AQKKEYFHKL INIGFKEIEV SFPSASQTDF DFTRYAVENA
     PDDVGIQCLV QSREHLIKRT VEALTGAKRA TIHTYLATSD MFREIVFNMS REEAISKAVE
     ATKLVRKLTK DDPSQQATRW SYEFSPECFS DTPGEFAVEI CEAVKKAWEP TEENPIIFNL
     PATVEVASPN VYADQIEYFS THITEREKVC ISTHCHNDRG CGVAATELGM LAGADRVEGC
     LFGNGERTGN VDLVTVAMNM YTQGVSPNLD FSDLTSISEI VHRCNKIPIP PRAPYGGELV
     VSAFSGSHQD AIKKGFAIQN KKQAQGETRW RIPYLPLDPK DIGRDYEAVI RVNSQSGKGG
     AAWVIMRSLG LDVPRPMQVD FSNTLQKNAD ALGRELKSEE ITKLFKETYN YNNNEHIYVT
     LLNYEVKKLN PERRALVGQV EINDKVVNIE GYGNGPISSL VDALSNLLNV KLSVQNYSEH
     SLGSGSATQA ASFINLSYIK DINNHATSNM WGVGVSEDTG DASIKAVFAT VNNIIHSGDV
     LLAE
//