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 05-DEC-2018, entry version 186. 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; GN ORFNames=L8003.22; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; 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; RA Gangloff S.P., Marguet D., Lauquin G.J.-M.; RT "Molecular cloning of the yeast mitochondrial aconitase gene (ACO1) RT and 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., RA Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., RA Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., RA Heumann K., Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., RA Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., RA Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., RA Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., RA Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., RA Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., RA Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., RA Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., RA 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., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT 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 RT small amounts is believing."; RL Mol. Biol. Cell 16:4163-4171(2005). RN [5] RP DISRUPTION PHENOTYPE. RX PubMed=10224250; RA Przybyla-Zawislak B., Gadde D.M., Ducharme K., McCammon M.T.; RT "Genetic and biochemical interactions involving tricarboxylic acid RT cycle (TCA) function using a collection of mutants defective in all RT TCA cycle 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., RA Dephoure N., 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 RT maintenance."; RL Science 307:714-717(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556, AND IDENTIFICATION RP BY 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 RP BY 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 RT to 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 RT and 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 RP BY 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 RT insights 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 RT requires two enzymes of the aconitase family for the isomerization of RT homocitrate to 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 RT with iron citrate toxicity."; RL Oxid. Med. Cell. Longev. 2013:493536-493536(2013). CC -!- FUNCTION: Catalyzes the isomerization of citrate to isocitrate via CC cis-aconitate, a step in the citric acid cycle. Can also provide CC minor contributions to the reversible dehydration of (R)- CC homocitrate to cis-homoaconitate, a step in the alpha-aminoadipate CC pathway for lysine biosynthesis. Plays also an essential role in CC mtDNA maintenance. May directly protect mtDNA from accumulation of CC point mutations and ssDNA breaks as a component of mitochondrial CC nucleoids, or by preventing accumulation of iron citrate thereby CC alleviating its detrimental effects in mitochondria. CC {ECO:0000269|PubMed:15692048, ECO:0000269|PubMed:17698960, CC ECO:0000269|PubMed:1972545, ECO:0000269|PubMed:23106124, CC ECO:0000269|PubMed:24066190}. CC -!- CATALYTIC ACTIVITY: CC Reaction=citrate = isocitrate; Xref=Rhea:RHEA:10336, CC ChEBI:CHEBI:16087, 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; CC 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; CC isocitrate from oxaloacetate: step 2/2. CC {ECO:0000269|PubMed:1972545}. CC -!- SUBUNIT: Monomer. Binds to mitochondrial DNA (mtDNA) and CC identified as component of mitochondrial nucleoids. CC {ECO:0000269|PubMed:15692048, ECO:0000269|PubMed:17698960}. CC -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly CC mitochondrial, small amounts are also detected in the cytosol with CC a ratio of 94:6. CC -!- INDUCTION: Highly induced in the absence of glutamate. Induction CC is further increased when both glutamate and lysine are missing. CC {ECO:0000269|PubMed:23106124}. CC -!- DISRUPTION PHENOTYPE: Essential for growth on nonfermentable CC carbon sources and for biosynthesis of glutamate. Causes a CC dramatic increase in cellular citrate levels. CC {ECO:0000269|PubMed:10224250, ECO:0000269|PubMed:18359281, CC ECO:0000269|PubMed:1972545}. CC -!- MISCELLANEOUS: The fermenting yeast S.cerevisiae has 2 aconitases, CC ACO1 essential for the citric acid cycle, and ACO2 specifically CC and exclusively contributing to lysine biosynthesis. In contrast, CC in respiring filamentous fungi the ACO2 homologs (acoB) seem CC enzymatically inactive and the ACO1 homolog (acoA) is solely CC responsible for these 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ProteinModelPortal; P19414; -. DR SMR; P19414; -. DR BioGrid; 31569; 201. 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_mRNA; YLR304C. DR GeneID; 851013; -. DR KEGG; sce:YLR304C; -. DR SGD; S000004295; ACO1. DR GeneTree; ENSGT00940000154892; -. DR HOGENOM; HOG000224293; -. DR InParanoid; P19414; -. DR KO; K01681; -. DR OMA; INLERMS; -. DR OrthoDB; EOG092C0DQS; -. DR BioCyc; MetaCyc:YLR304C-MONOMER; -. DR BioCyc; YEAST:YLR304C-MONOMER; -. DR Reactome; R-SCE-71403; Citric acid cycle (TCA cycle). DR Reactome; R-SCE-917937; Iron uptake and transport. DR UniPathway; UPA00223; UER00718. DR PRO; PR:P19414; -. DR Proteomes; UP000002311; Chromosome XII. 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; IBA:GO_Central. 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:0003690; F:double-stranded DNA binding; IDA:SGD. 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; Complete proteome; Cytoplasm; Direct protein sequencing; Iron; KW Iron-sulfur; Lyase; Metal-binding; Mitochondrion; Phosphoprotein; KW Reference proteome; Transit peptide; Tricarboxylic acid cycle. FT TRANSIT 1 16 Mitochondrion. FT {ECO:0000269|PubMed:15975908}. FT CHAIN 17 778 Aconitate hydratase, mitochondrial. FT /FTId=PRO_0000000547. FT REGION 188 190 Substrate binding. {ECO:0000250}. FT REGION 667 668 Substrate binding. {ECO:0000250}. FT METAL 382 382 Iron-sulfur (4Fe-4S). {ECO:0000250}. FT METAL 445 445 Iron-sulfur (4Fe-4S). {ECO:0000250}. FT METAL 448 448 Iron-sulfur (4Fe-4S). {ECO:0000250}. FT BINDING 95 95 Substrate. {ECO:0000250}. FT BINDING 471 471 Substrate. {ECO:0000250}. FT BINDING 476 476 Substrate. {ECO:0000250}. FT BINDING 604 604 Substrate. {ECO:0000250}. FT MOD_RES 391 391 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 409 409 Phosphothreonine. FT {ECO:0000244|PubMed:17761666}. FT MOD_RES 556 556 Phosphoserine. FT {ECO:0000244|PubMed:17330950}. FT MUTAGEN 604 604 R->K: Strongly diminishes the catalytic FT activity towards both known substrates, FT aconitate and homoaconitate. FT {ECO:0000269|PubMed:23106124}. FT CONFLICT 527 549 DGLPQRGYDAGENTYQAPPADRS -> RWFASKEVMMLVRT FT LTKLHLQTVA (in Ref. 1; AAA34389). FT {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 //