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Database: UniProt
Entry: P19414
LinkDB: P19414
Original site: P19414 
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   09-JUL-2014, entry version 142.
DE   RecName: Full=Aconitate hydratase, mitochondrial;
DE            Short=Aconitase;
DE            EC=4.2.1.3;
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, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 44774 / DBY747;
RX   PubMed=1972545;
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   -!- CATALYTIC ACTIVITY: Citrate = isocitrate.
CC   -!- COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity).
CC   -!- ENZYME REGULATION: Subject to catabolite regulation.
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle;
CC       isocitrate from oxaloacetate: step 2/2.
CC   -!- SUBUNIT: Monomer. Binds to mitochondrial DNA (mtDNA) and
CC       identified as component of mitochondrial nucleoids.
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   -!- 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   -!- 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.
CC   -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
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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   ProteinModelPortal; P19414; -.
DR   SMR; P19414; 26-778.
DR   BioGrid; 31569; 171.
DR   DIP; DIP-4679N; -.
DR   IntAct; P19414; 9.
DR   MINT; MINT-557728; -.
DR   STRING; 4932.YLR304C; -.
DR   MaxQB; P19414; -.
DR   PaxDb; P19414; -.
DR   PeptideAtlas; P19414; -.
DR   PRIDE; P19414; -.
DR   EnsemblFungi; YLR304C; YLR304C; YLR304C.
DR   GeneID; 851013; -.
DR   KEGG; sce:YLR304C; -.
DR   CYGD; YLR304c; -.
DR   SGD; S000004295; ACO1.
DR   eggNOG; COG1048; -.
DR   GeneTree; ENSGT00730000111046; -.
DR   HOGENOM; HOG000224293; -.
DR   KO; K01681; -.
DR   OMA; ANGNEFK; -.
DR   OrthoDB; EOG7X6M7Q; -.
DR   BioCyc; MetaCyc:YLR304C-MONOMER; -.
DR   BioCyc; YEAST:YLR304C-MONOMER; -.
DR   Reactome; REACT_118590; Mitochondrial Protein Import (yeast).
DR   UniPathway; UPA00223; UER00718.
DR   NextBio; 967571; -.
DR   PRO; PR:P19414; -.
DR   Genevestigator; P19414; -.
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:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
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; IPR015937; Acoase/IPM_deHydtase.
DR   InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR   InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR   InterPro; IPR015932; Aconitase/IPMdHydase_lsu_aba_2.
DR   InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR   InterPro; IPR006248; Aconitase_mito-like.
DR   InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR   PANTHER; PTHR11670; PTHR11670; 1.
DR   Pfam; PF00330; Aconitase; 1.
DR   Pfam; PF00694; Aconitase_C; 1.
DR   PRINTS; PR00415; ACONITASE.
DR   SUPFAM; SSF52016; SSF52016; 1.
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   CHAIN        17    778       Aconitate hydratase, mitochondrial.
FT                                /FTId=PRO_0000000547.
FT   REGION      188    190       Substrate binding (By similarity).
FT   REGION      667    668       Substrate binding (By similarity).
FT   METAL       382    382       Iron-sulfur (4Fe-4S) (By similarity).
FT   METAL       445    445       Iron-sulfur (4Fe-4S) (By similarity).
FT   METAL       448    448       Iron-sulfur (4Fe-4S) (By similarity).
FT   BINDING      95     95       Substrate (By similarity).
FT   BINDING     471    471       Substrate (By similarity).
FT   BINDING     476    476       Substrate (By similarity).
FT   BINDING     604    604       Substrate (By similarity).
FT   MOD_RES     391    391       Phosphoserine.
FT   MOD_RES     409    409       Phosphothreonine.
FT   MOD_RES     556    556       Phosphoserine.
FT   MUTAGEN     604    604       R->K: Strongly diminishes the catalytic
FT                                activity towards both known substrates,
FT                                aconitate and homoaconitate.
FT   CONFLICT    527    549       DGLPQRGYDAGENTYQAPPADRS -> RWFASKEVMMLVRT
FT                                LTKLHLQTVA (in Ref. 1; AAA34389).
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
//
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