ACON2_YEAST
ID ACON2_YEAST Reviewed; 789 AA.
AC P39533; D6VVZ3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Homocitrate dehydratase, mitochondrial;
DE EC=4.2.1.-;
DE AltName: Full=Aconitase 2;
DE Flags: Precursor;
GN Name=ACO2; OrderedLocusNames=YJL200C; ORFNames=J0327;
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].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7754713; DOI=10.1002/yea.320100912;
RA Purnelle B., Coster F., Goffeau A.;
RT "The sequence of a 36 kb segment on the left arm of yeast chromosome X
RT identifies 24 open reading frames including NUC1, PRP21 (SPP91), CDC6,
RT CRY2, the gene for S24, a homologue to the aconitase gene ACO1 and two
RT homologues to chromosome III genes.";
RL Yeast 10:1235-1249(1994).
RN [2]
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 [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 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 [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].
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [8]
RP FUNCTION, INDUCTION, AND MUTAGENESIS OF LYS-610.
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).
CC -!- FUNCTION: Catalyzes the reversible dehydration of (R)-homocitrate to
CC cis-homoaconitate, a step in the alpha-aminoadipate pathway for lysine
CC biosynthesis. {ECO:0000269|PubMed:23106124}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-homocitrate = cis-homoaconitate + H2O;
CC Xref=Rhea:RHEA:26101, ChEBI:CHEBI:15377, ChEBI:CHEBI:58174,
CC ChEBI:CHEBI:58884;
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 -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 2/5.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:14576278}.
CC -!- INDUCTION: Constitutively expressed with a small induction when both
CC glutamate and lysine are missing. {ECO:0000269|PubMed:23106124}.
CC -!- DISRUPTION PHENOTYPE: Has very little effect on growth on
CC nonfermentable carbon sources. {ECO:0000269|PubMed:10224250}.
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 4670 molecules/cell in log phase SD medium.
CC {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; X77688; CAA54757.1; -; Genomic_DNA.
DR EMBL; Z49475; CAA89495.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08609.1; -; Genomic_DNA.
DR PIR; S46631; S46631.
DR RefSeq; NP_012335.1; NM_001181633.1.
DR AlphaFoldDB; P39533; -.
DR SMR; P39533; -.
DR BioGRID; 33557; 78.
DR DIP; DIP-1376N; -.
DR IntAct; P39533; 8.
DR MINT; P39533; -.
DR STRING; 4932.YJL200C; -.
DR MoonProt; P39533; -.
DR iPTMnet; P39533; -.
DR MaxQB; P39533; -.
DR PaxDb; P39533; -.
DR PRIDE; P39533; -.
DR EnsemblFungi; YJL200C_mRNA; YJL200C; YJL200C.
DR GeneID; 853230; -.
DR KEGG; sce:YJL200C; -.
DR SGD; S000003736; ACO2.
DR VEuPathDB; FungiDB:YJL200C; -.
DR eggNOG; KOG0453; Eukaryota.
DR GeneTree; ENSGT00960000189203; -.
DR HOGENOM; CLU_006714_2_2_1; -.
DR InParanoid; P39533; -.
DR OMA; GRASYMR; -.
DR BioCyc; YEAST:YJL200C-MON; -.
DR UniPathway; UPA00033; UER00029.
DR PRO; PR:P39533; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P39533; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; ISS:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IMP: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; Amino-acid biosynthesis; Iron; Iron-sulfur; Lyase;
KW Lysine biosynthesis; Metal-binding; Mitochondrion; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..14
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 15..789
FT /note="Homocitrate dehydratase, mitochondrial"
FT /id="PRO_0000076649"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 189..191
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 385
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 451
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 476
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 481
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 672..673
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MUTAGEN 610
FT /note="K->R: Reduces catalytic activity towards
FT homoaconitate by 45% and increases the activity towards
FT aconitate by a factor 116."
FT /evidence="ECO:0000269|PubMed:23106124"
SQ SEQUENCE 789 AA; 86583 MW; FABA4FE482D3F993 CRC64;
MLSSANRFYI KRHLATHANM FPSVSKNFQT KVPPYAKLLT NLDKIKQITN NAPLTLAEKI
LYSHLCDPEE SITSSDLSTI RGNKYLKLNP DRVAMQDASA QMALLQFMTT GLNQTSVPAS
IHCDHLIVGK DGETKDLPSS IATNQEVFDF LESCAKRYGI QFWGPGSGII HQIVLENFSA
PGLMMLGTDS HTPNAGGLGA IAIGVGGADA VDALTGTPWE LKAPKILGVK LTGKLNGWST
PKDVITKLAG LLTVRGGTGY IVEYFGEGVS TLSCTGMATI CNMGAEIGAT TSTFPYQEAH
KRYLQATNRA EVAEAADVAL NKFNFLRADK DAQYDKVIEI DLSAIEPHVN GPFTPDLSTP
ISQYAEKSLK ENWPQKVSAG LIGSCTNSSY QDMSRVVDLV KQASKAGLKP RIPFFVTPGS
EQIRATLERD GIIDIFQENG AKVLANACGP CIGQWNREDV SKTSKETNTI FTSFNRNFRA
RNDGNRNTMN FLTSPEIVTA MSYSGDAQFN PLTDSIKLPN GKDFKFQPPK GDELPKRGFE
HGRDKFYPEM DPKPDSNVEI KVDPNSDRLQ LLEPFKPWNG KELKTNVLLK VEGKCTTDHI
SAAGVWLKYK GHLENISYNT LIGAQNKETG EVNKAYDLDG TEYDIPGLMM KWKSDGRPWT
VIAEHNYGEG SAREHAALSP RFLGGEILLV KSFARIHETN LKKQGVLPLT FANESDYDKI
SSGDVLETLN LVDMIAKDGN NGGEIDVKIT KPNGESFTIK AKHTMSKDQI DFFKAGSAIN
YIGNIRRNE
