ACON_YEAST
ID ACON_YEAST Reviewed; 778 AA.
AC P19414; D6VYU7;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Aconitate hydratase, mitochondrial;
DE Short=Aconitase;
DE EC=4.2.1.3 {ECO:0000269|PubMed:1972545};
DE AltName: Full=Citrate hydro-lyase;
DE Flags: Precursor;
GN Name=ACO1; Synonyms=GLU1; OrderedLocusNames=YLR304C; ORFNames=L8003.22;
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], FUNCTION, DISRUPTION PHENOTYPE, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=ATCC 44774 / DBY747;
RX PubMed=1972545; DOI=10.1128/mcb.10.7.3551-3561.1990;
RA Gangloff S.P., Marguet D., Lauquin G.J.-M.;
RT "Molecular cloning of the yeast mitochondrial aconitase gene (ACO1) and
RT evidence of a synergistic regulation of expression by glucose plus
RT glutamate.";
RL Mol. Cell. Biol. 10:3551-3561(1990).
RN [2]
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 [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 PROTEIN SEQUENCE OF 17-23, AND SUBCELLULAR LOCATION.
RX PubMed=15975908; DOI=10.1091/mbc.e04-11-1028;
RA Regev-Rudzki N., Karniely S., Ben-Haim N.N., Pines O.;
RT "Yeast aconitase in two locations and two metabolic pathways: seeing small
RT amounts is believing.";
RL Mol. Biol. Cell 16:4163-4171(2005).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=10224250; DOI=10.1093/genetics/152.1.153;
RA Przybyla-Zawislak B., Gadde D.M., Ducharme K., McCammon M.T.;
RT "Genetic and biochemical interactions involving tricarboxylic acid cycle
RT (TCA) function using a collection of mutants defective in all TCA cycle
RT genes.";
RL Genetics 152:153-166(1999).
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 FUNCTION, AND SUBUNIT.
RX PubMed=15692048; DOI=10.1126/science.1106391;
RA Chen X.J., Wang X., Kaufman B.A., Butow R.A.;
RT "Aconitase couples metabolic regulation to mitochondrial DNA maintenance.";
RL Science 307:714-717(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-409, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT phosphorylation in assembly of the ATP synthase.";
RL Mol. Cell. Proteomics 6:1896-1906(2007).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=17698960; DOI=10.1073/pnas.0703078104;
RA Chen X.J., Wang X., Butow R.A.;
RT "Yeast aconitase binds and provides metabolically coupled protection to
RT mitochondrial DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13738-13743(2007).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=18359281; DOI=10.1016/j.abb.2008.03.005;
RA Lin A.P., Hakala K.W., Weintraub S.T., McAlister-Henn L.;
RT "Suppression of metabolic defects of yeast isocitrate dehydrogenase and
RT aconitase mutants by loss of citrate synthase.";
RL Arch. Biochem. Biophys. 474:205-212(2008).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=18577574; DOI=10.1242/jcs.029207;
RA Regev-Rudzki N., Yogev O., Pines O.;
RT "The mitochondrial targeting sequence tilts the balance between
RT mitochondrial and cytosolic dual localization.";
RL J. Cell Sci. 121:2423-2431(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=21440554; DOI=10.1016/j.jmb.2011.03.045;
RA Ben-Menachem R., Regev-Rudzki N., Pines O.;
RT "The aconitase C-terminal domain is an independent dual targeting
RT element.";
RL J. Mol. Biol. 409:113-123(2011).
RN [15]
RP FUNCTION, INDUCTION, AND MUTAGENESIS OF ARG-604.
RX PubMed=23106124; DOI=10.1111/mmi.12076;
RA Fazius F., Shelest E., Gebhardt P., Brock M.;
RT "The fungal alpha-aminoadipate pathway for lysine biosynthesis requires two
RT enzymes of the aconitase family for the isomerization of homocitrate to
RT homoisocitrate.";
RL Mol. Microbiol. 86:1508-1530(2012).
RN [16]
RP FUNCTION.
RX PubMed=24066190; DOI=10.1155/2013/493536;
RA Farooq M.A., Pracheil T.M., Dong Z., Xiao F., Liu Z.;
RT "Mitochondrial DNA instability in cells lacking aconitase correlates with
RT iron citrate toxicity.";
RL Oxid. Med. Cell. Longev. 2013:493536-493536(2013).
CC -!- FUNCTION: Catalyzes the isomerization of citrate to isocitrate via cis-
CC aconitate, a step in the citric acid cycle. Can also provide minor
CC contributions to the reversible dehydration of (R)-homocitrate to cis-
CC homoaconitate, a step in the alpha-aminoadipate pathway for lysine
CC biosynthesis. Also plays an essential role in mtDNA maintenance. May
CC directly protect mtDNA from accumulation of point mutations and ssDNA
CC breaks as a component of mitochondrial nucleoids, or by preventing
CC accumulation of iron citrate thereby alleviating its detrimental
CC effects in mitochondria. {ECO:0000269|PubMed:15692048,
CC ECO:0000269|PubMed:17698960, ECO:0000269|PubMed:1972545,
CC ECO:0000269|PubMed:23106124, ECO:0000269|PubMed:24066190}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336,
CC ChEBI:CHEBI:15562, ChEBI:CHEBI:16947; EC=4.2.1.3;
CC Evidence={ECO:0000269|PubMed:1972545};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Subject to catabolite regulation.
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 2/2. {ECO:0000269|PubMed:1972545}.
CC -!- SUBUNIT: Monomer. Binds to mitochondrial DNA (mtDNA) and identified as
CC component of mitochondrial nucleoids. {ECO:0000269|PubMed:15692048,
CC ECO:0000269|PubMed:17698960}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly
CC mitochondrial, small amounts are also detected in the cytosol with a
CC ratio of 94:6.
CC -!- INDUCTION: Highly induced in the absence of glutamate. Induction is
CC further increased when both glutamate and lysine are missing.
CC {ECO:0000269|PubMed:23106124}.
CC -!- DISRUPTION PHENOTYPE: Essential for growth on nonfermentable carbon
CC sources and for biosynthesis of glutamate. Causes a dramatic increase
CC in cellular citrate levels. {ECO:0000269|PubMed:10224250,
CC ECO:0000269|PubMed:18359281, ECO:0000269|PubMed:1972545}.
CC -!- MISCELLANEOUS: The fermenting yeast S.cerevisiae has 2 aconitases, ACO1
CC essential for the citric acid cycle, and ACO2 specifically and
CC exclusively contributing to lysine biosynthesis. In contrast, in
CC respiring filamentous fungi the ACO2 homologs (acoB) seem enzymatically
CC inactive and the ACO1 homolog (acoA) is solely responsible for these
CC functions.
CC -!- MISCELLANEOUS: Present with 96700 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; M33131; AAA34389.1; -; Genomic_DNA.
DR EMBL; U17243; AAB67348.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09613.1; -; Genomic_DNA.
DR PIR; S50387; S50387.
DR RefSeq; NP_013407.1; NM_001182192.1.
DR AlphaFoldDB; P19414; -.
DR SMR; P19414; -.
DR BioGRID; 31569; 220.
DR DIP; DIP-4679N; -.
DR IntAct; P19414; 33.
DR MINT; P19414; -.
DR STRING; 4932.YLR304C; -.
DR MoonDB; P19414; Curated.
DR iPTMnet; P19414; -.
DR MaxQB; P19414; -.
DR PaxDb; P19414; -.
DR PRIDE; P19414; -.
DR TopDownProteomics; P19414; -.
DR EnsemblFungi; YLR304C_mRNA; YLR304C; YLR304C.
DR GeneID; 851013; -.
DR KEGG; sce:YLR304C; -.
DR SGD; S000004295; ACO1.
DR VEuPathDB; FungiDB:YLR304C; -.
DR eggNOG; KOG0453; Eukaryota.
DR GeneTree; ENSGT00940000154892; -.
DR HOGENOM; CLU_006714_2_2_1; -.
DR InParanoid; P19414; -.
DR OMA; GCIGMGQ; -.
DR BioCyc; MetaCyc:YLR304C-MON; -.
DR BioCyc; YEAST:YLR304C-MON; -.
DR BRENDA; 4.2.1.3; 984.
DR Reactome; R-SCE-71403; Citric acid cycle (TCA cycle).
DR UniPathway; UPA00223; UER00718.
DR PRO; PR:P19414; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P19414; protein.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:SGD.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:SGD.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:SGD.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:SGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:SGD.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR Gene3D; 3.40.1060.10; -; 1.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR015932; Aconitase_dom2.
DR InterPro; IPR006248; Aconitase_mito-like.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01340; aconitase_mito; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Cytoplasm; Direct protein sequencing; Iron; Iron-sulfur; Lyase;
KW Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome;
KW Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..16
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:15975908"
FT CHAIN 17..778
FT /note="Aconitate hydratase, mitochondrial"
FT /id="PRO_0000000547"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 188..190
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 382
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 445
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 448
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 471
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 476
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 604
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 667..668
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 409
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17761666"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MUTAGEN 604
FT /note="R->K: Strongly diminishes the catalytic activity
FT towards both known substrates, aconitate and
FT homoaconitate."
FT /evidence="ECO:0000269|PubMed:23106124"
FT CONFLICT 527..549
FT /note="DGLPQRGYDAGENTYQAPPADRS -> RWFASKEVMMLVRTLTKLHLQTVA
FT (in Ref. 1; AAA34389)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 778 AA; 85368 MW; AA9EB9A24388090E CRC64;
MLSARSAIKR PIVRGLATVS NLTRDSKVNQ NLLEDHSFIN YKQNVETLDI VRKRLNRPFT
YAEKILYGHL DDPHGQDIQR GVSYLKLRPD RVACQDATAQ MAILQFMSAG LPQVAKPVTV
HCDHLIQAQV GGEKDLKRAI DLNKEVYDFL ASATAKYNMG FWKPGSGIIH QIVLENYAFP
GALIIGTDSH TPNAGGLGQL AIGVGGADAV DVMAGRPWEL KAPKILGVKL TGKMNGWTSP
KDIILKLAGI TTVKGGTGKI VEYFGDGVDT FSATGMGTIC NMGAEIGATT SVFPFNKSMI
EYLEATGRGK IADFAKLYHK DLLSADKDAE YDEVVEIDLN TLEPYINGPF TPDLATPVSK
MKEVAVANNW PLDVRVGLIG SCTNSSYEDM SRSASIVKDA AAHGLKSKTI FTVTPGSEQI
RATIERDGQL ETFKEFGGIV LANACGPCIG QWDRRDIKKG DKNTIVSSYN RNFTSRNDGN
PQTHAFVASP ELVTAFAIAG DLRFNPLTDK LKDKDGNEFM LKPPHGDGLP QRGYDAGENT
YQAPPADRST VEVKVSPTSD RLQLLKPFKP WDGKDAKDMP ILIKAVGKTT TDHISMAGPW
LKYRGHLENI SNNYMIGAIN AENKKANCVK NVYTGEYKGV PDTARDYRDQ GIKWVVIGDE
NFGEGSSREH AALEPRFLGG FAIITKSFAR IHETNLKKQG LLPLNFKNPA DYDKINPDDR
IDILGLAELA PGKPVTMRVH PKNGKPWDAV LTHTFNDEQI EWFKYGSALN KIKADEKK
