CISY1_YEAST
ID CISY1_YEAST Reviewed; 479 AA.
AC P00890; D6W1H7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Citrate synthase, mitochondrial {ECO:0000303|PubMed:6090126};
DE EC=2.3.3.1 {ECO:0000269|PubMed:17570335, ECO:0000269|PubMed:28076776};
DE Flags: Precursor;
GN Name=CIT1 {ECO:0000303|PubMed:6090126}; Synonyms=GLU3, LYS6;
GN OrderedLocusNames=YNR001C; ORFNames=N2019;
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 24657 / D273-10B;
RX PubMed=6090126; DOI=10.1002/j.1460-2075.1984.tb02045.x;
RA Suissa M., Suda K., Schatz G.;
RT "Isolation of the nuclear yeast genes for citrate synthase and fifteen
RT other mitochondrial proteins by a new screening method.";
RL EMBO J. 3:1773-1781(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 24657 / D273-10B;
RA Lindner P., Plueckthun A.;
RT "The effect of point mutations in the hinge of yeast citrate synthase.";
RL Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=S288c / GRF88;
RX PubMed=7941739; DOI=10.1002/yea.320100412;
RA Lalo D., Stettler S., Mariotte S., Gendreau E., Thuriaux P.;
RT "Organization of the centromeric region of chromosome XIV in Saccharomyces
RT cerevisiae.";
RL Yeast 10:523-533(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=7900425; DOI=10.1002/yea.320101013;
RA Verhasselt P., Aert R., Voet M., Volckaert G.;
RT "Twelve open reading frames revealed in the 23.6 kb segment flanking the
RT centromere on the Saccharomyces cerevisiae chromosome XIV right arm.";
RL Yeast 10:1355-1361(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11502169; DOI=10.1021/bi010277r;
RA Grandier-Vazeille X., Bathany K., Chaignepain S., Camougrand N., Manon S.,
RA Schmitter J.-M.;
RT "Yeast mitochondrial dehydrogenases are associated in a supramolecular
RT complex.";
RL Biochemistry 40:9758-9769(2001).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17570335; DOI=10.1016/j.abb.2007.04.039;
RA Graybill E.R., Rouhier M.F., Kirby C.E., Hawes J.W.;
RT "Functional comparison of citrate synthase isoforms from S. cerevisiae.";
RL Arch. Biochem. Biophys. 465:26-37(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, PHOSPHORYLATION AT
RP SER-462, DEPHOSPHORYLATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP SER-462.
RX PubMed=28076776; DOI=10.1016/j.celrep.2016.12.049;
RA Guo X., Niemi N.M., Hutchins P.D., Condon S.G.F., Jochem A., Ulbrich A.,
RA Higbee A.J., Russell J.D., Senes A., Coon J.J., Pagliarini D.J.;
RT "Ptc7p Dephosphorylates Select Mitochondrial Proteins to Enhance Metabolic
RT Function.";
RL Cell Rep. 18:307-313(2017).
CC -!- FUNCTION: Specific citrate synthase with catalytic activity only with
CC acetyl-CoA. {ECO:0000269|PubMed:17570335, ECO:0000269|PubMed:28076776}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H2O + oxaloacetate = citrate + CoA + H(+);
CC Xref=Rhea:RHEA:16845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288; EC=2.3.3.1; Evidence={ECO:0000269|PubMed:17570335,
CC ECO:0000269|PubMed:28076776};
CC -!- ACTIVITY REGULATION: Phosphorylation at Ser-462 inhibits catalytic
CC activity. Dephosphorylation at Ser-462 by PTC7 enhances catalytic
CC activity. {ECO:0000269|PubMed:28076776}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=76 uM for acetyl-CoA {ECO:0000269|PubMed:17570335};
CC KM=9.86 uM for oxaloacetate {ECO:0000269|PubMed:28076776};
CC Vmax=1.92 uM/sec/ug enzyme {ECO:0000269|PubMed:28076776};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 1/2. {ECO:0000305}.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:28076776). Exists as an inactive
CC monomer when phosphorylated (PubMed:28076776). Homodimerization is
CC dependent on dephosphorylation of Ser-462 by PTC7 and is required for
CC activity (PubMed:28076776). {ECO:0000269|PubMed:28076776}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:11502169}.
CC -!- PTM: Phosphorylation at Ser-462. Dephosphorylated at Ser-462 by PTC7.
CC {ECO:0000269|PubMed:28076776}.
CC -!- DISRUPTION PHENOTYPE: Decreased growth related to mitochondrial
CC dysfunction. {ECO:0000269|PubMed:28076776}.
CC -!- MISCELLANEOUS: Citrate synthase is found in nearly all cells capable of
CC oxidative metabolism. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {ECO:0000305}.
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DR EMBL; X00782; CAA25359.1; -; Genomic_DNA.
DR EMBL; Z23259; CAA80781.1; -; Genomic_DNA.
DR EMBL; X77395; CAA54569.1; -; Genomic_DNA.
DR EMBL; Z71616; CAA96277.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10543.1; -; Genomic_DNA.
DR PIR; S35390; YKBY.
DR RefSeq; NP_014398.1; NM_001183178.1.
DR AlphaFoldDB; P00890; -.
DR SMR; P00890; -.
DR BioGRID; 35825; 155.
DR DIP; DIP-4597N; -.
DR IntAct; P00890; 31.
DR STRING; 4932.YNR001C; -.
DR iPTMnet; P00890; -.
DR MaxQB; P00890; -.
DR PaxDb; P00890; -.
DR PRIDE; P00890; -.
DR TopDownProteomics; P00890; -.
DR EnsemblFungi; YNR001C_mRNA; YNR001C; YNR001C.
DR GeneID; 855732; -.
DR KEGG; sce:YNR001C; -.
DR SGD; S000005284; CIT1.
DR VEuPathDB; FungiDB:YNR001C; -.
DR eggNOG; KOG2617; Eukaryota.
DR GeneTree; ENSGT00390000006813; -.
DR HOGENOM; CLU_022049_2_1_1; -.
DR InParanoid; P00890; -.
DR OMA; TVGWCAQ; -.
DR BioCyc; YEAST:YNR001C-MON; -.
DR BRENDA; 2.3.3.16; 984.
DR Reactome; R-SCE-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; P00890; -.
DR UniPathway; UPA00223; UER00717.
DR PRO; PR:P00890; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P00890; protein.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0004108; F:citrate (Si)-synthase activity; IDA:SGD.
DR GO; GO:0036440; F:citrate synthase activity; IMP:UniProtKB.
DR GO; GO:0046356; P:acetyl-CoA catabolic process; IDA:SGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IBA:GO_Central.
DR GO; GO:0006101; P:citrate metabolic process; IGI:SGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 1.10.580.10; -; 1.
DR InterPro; IPR016142; Citrate_synth-like_lrg_a-sub.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase.
DR InterPro; IPR019810; Citrate_synthase_AS.
DR InterPro; IPR010109; Citrate_synthase_euk.
DR InterPro; IPR036969; Citrate_synthase_sf.
DR PANTHER; PTHR11739; PTHR11739; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR PRINTS; PR00143; CITRTSNTHASE.
DR SUPFAM; SSF48256; SSF48256; 1.
DR TIGRFAMs; TIGR01793; cit_synth_euk; 1.
DR PROSITE; PS00480; CITRATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Mitochondrion; Phosphoprotein;
KW Reference proteome; Transferase; Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..37
FT /note="Mitochondrion"
FT CHAIN 38..479
FT /note="Citrate synthase, mitochondrial"
FT /id="PRO_0000005479"
FT ACT_SITE 312
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT ACT_SITE 358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT ACT_SITE 413
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28076776"
FT MUTAGEN 462
FT /note="S->A: Loss of phosphorylation. Greatly increases
FT catalytic activity and promotes homodimerization."
FT /evidence="ECO:0000269|PubMed:28076776"
FT MUTAGEN 462
FT /note="S->E: Phosphomimetic mutant. Inhibits catalytic
FT activity and homodimerization."
FT /evidence="ECO:0000269|PubMed:28076776"
FT CONFLICT 58
FT /note="E -> Q (in Ref. 1; CAA25359)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="E -> EE (in Ref. 1; CAA25359)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 53360 MW; 280661B1CB248F14 CRC64;
MSAILSTTSK SFLSRGSTRQ CQNMQKALFA LLNARHYSSA SEQTLKERFA EIIPAKAEEI
KKFKKEHGKT VIGEVLLEQA YGGMRGIKGL VWEGSVLDPE EGIRFRGRTI PEIQRELPKA
EGSTEPLPEA LFWLLLTGEI PTDAQVKALS ADLAARSEIP EHVIQLLDSL PKDLHPMAQF
SIAVTALESE SKFAKAYAQG VSKKEYWSYT FEDSLDLLGK LPVIASKIYR NVFKDGKITS
TDPNADYGKN LAQLLGYENK DFIDLMRLYL TIHSDHEGGN VSAHTTHLVG SALSSPYLSL
AAGLNGLAGP LHGRANQEVL EWLFKLREEV KGDYSKETIE KYLWDTLNAG RVVPGYGHAV
LRKTDPRYTA QREFALKHFP DYELFKLVST IYEVAPGVLT KHGKTKNPWP NVDSHSGVLL
QYYGLTEASF YTVLFGVARA IGVLPQLIID RAVGAPIERP KSFSTEKYKE LVKKIESKN
