CISY2_YEAST
ID CISY2_YEAST Reviewed; 460 AA.
AC P08679; D6VR15;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Citrate synthase, peroxisomal {ECO:0000303|PubMed:3023912};
DE EC=2.3.3.16 {ECO:0000269|PubMed:3023912};
GN Name=CIT2 {ECO:0000303|PubMed:3023912}; OrderedLocusNames=YCR005C;
GN ORFNames=YCR043, YCR5C;
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].
RX PubMed=3540614; DOI=10.1128/mcb.6.12.4509-4515.1986;
RA Rosenkrantz M., Alam T., Kim K.-S., Clark B.J., Srere P.A., Guarente L.P.;
RT "Mitochondrial and nonmitochondrial citrate synthases in Saccharomyces
RT cerevisiae are encoded by distinct homologous genes.";
RL Mol. Cell. Biol. 6:4509-4515(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1580102; DOI=10.1002/yea.320080107;
RA Biteau N., Fremaux C., Hebrard S., Menara A., Aigle M., Crouzet M.;
RT "The complete sequence of a 10.8kb fragment to the right of the chromosome
RT III centromere of Saccharomyces cerevisiae.";
RL Yeast 8:61-70(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1574125; DOI=10.1038/357038a0;
RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA Sgouros J.G.;
RT "The complete DNA sequence of yeast chromosome III.";
RL Nature 357:38-46(1992).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX PubMed=1986232; DOI=10.1128/mcb.11.1.38-46.1991;
RA Liao X., Small W.C., Srere P.A., Butow R.A.;
RT "Intramitochondrial functions regulate nonmitochondrial citrate synthase
RT (CIT2) expression in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 11:38-46(1991).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=3023912; DOI=10.1128/mcb.6.6.1936-1942.1986;
RA Kim K.S., Rosenkrantz M.S., Guarente L.;
RT "Saccharomyces cerevisiae contains two functional citrate synthase genes.";
RL Mol. Cell. Biol. 6:1936-1942(1986).
RN [8]
RP DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=2181273; DOI=10.1128/mcb.10.4.1399-1405.1990;
RA Lewin A.S., Hines V., Small G.M.;
RT "Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is
RT peroxisomal.";
RL Mol. Cell. Biol. 10:1399-1405(1990).
RN [9]
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 [10]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-354 AND LYS-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=SUB592;
RX PubMed=12872131; DOI=10.1038/nbt849;
RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G.,
RA Roelofs J., Finley D., Gygi S.P.;
RT "A proteomics approach to understanding protein ubiquitination.";
RL Nat. Biotechnol. 21:921-926(2003).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, 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 [12]
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 [13]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-218 AND LYS-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [14]
RP FUNCTION, INTERACTION WITH UCC1, SUBCELLULAR LOCATION, INDUCTION,
RP UBIQUITINATION, AND MUTAGENESIS OF HIS-293; GLY-294 AND HIS-339.
RX PubMed=25982115; DOI=10.1016/j.molcel.2015.04.013;
RA Nakatsukasa K., Nishimura T., Byrne S.D., Okamoto M.,
RA Takahashi-Nakaguchi A., Chibana H., Okumura F., Kamura T.;
RT "The ubiquitin ligase SCF(Ucc1) acts as a metabolic switch for the
RT glyoxylate cycle.";
RL Mol. Cell 59:22-34(2015).
CC -!- FUNCTION: Peroxisomal citrate synthase involved in the citrate
CC homeostasis (PubMed:3023912, PubMed:25982115). Catalyzes the
CC condensation of acetyl coenzyme A and oxaloacetate to form citrate
CC (PubMed:3023912, PubMed:25982115). Citrate synthase is the rate-
CC limiting enzyme of the tricarboxylic acid (TCA) cycle (Probable).
CC {ECO:0000269|PubMed:25982115, ECO:0000269|PubMed:3023912,
CC ECO:0000305|PubMed:3023912}.
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=2.3.3.16; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10117, ECO:0000269|PubMed:3023912};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 1/2. {ECO:0000269|PubMed:3023912}.
CC -!- SUBUNIT: Interacts with F-box protein UCC1.
CC {ECO:0000269|PubMed:25982115}.
CC -!- INTERACTION:
CC P08679; P08679: CIT2; NbExp=3; IntAct=EBI-4713, EBI-4713;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25982115}.
CC Peroxisome {ECO:0000269|PubMed:2181273, ECO:0000269|PubMed:25982115}.
CC -!- INDUCTION: Expression is repressed in medium containing both glucose
CC and glutamate (PubMed:3023912). Expression is up-regulated by the
CC presence of C2-compounds such as acetate (PubMed:25982115).
CC {ECO:0000269|PubMed:25982115, ECO:0000269|PubMed:3023912}.
CC -!- PTM: Ubiquitinated by the E3 ubiquitin-protein ligase complex
CC SCF(UCC1), which leads to its degradation by the proteasome
CC (PubMed:25982115). Ubiquitination is prevented by oxaloacetate,
CC suggesting the existence of an oxaloacetate-dependent positive feedback
CC loop that stabilizes CIT2 (PubMed:25982115).
CC {ECO:0000269|PubMed:25982115}.
CC -!- DISRUPTION PHENOTYPE: Leads to glutamate auxotrophy and poor growth on
CC rich medium containing lactate, a nonfermentable carbon source, when
CC CIT1 is also deleted. {ECO:0000269|PubMed:3023912}.
CC -!- MISCELLANEOUS: Citrate synthase is found in nearly all cells capable of
CC oxidative metabolism. {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 2310 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the citrate synthase family. {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; Z11113; CAA77442.1; -; Genomic_DNA.
DR EMBL; M14686; AAA34497.1; -; Genomic_DNA.
DR EMBL; X59720; CAA42342.1; -; Genomic_DNA.
DR EMBL; AY692837; AAT92856.1; -; Genomic_DNA.
DR EMBL; M54982; AAA34498.1; -; Genomic_DNA.
DR EMBL; BK006937; DAA07484.1; -; Genomic_DNA.
DR PIR; A25393; YKBYC.
DR RefSeq; NP_009931.1; NM_001178718.1.
DR AlphaFoldDB; P08679; -.
DR SMR; P08679; -.
DR BioGRID; 30983; 113.
DR DIP; DIP-1259N; -.
DR IntAct; P08679; 5.
DR MINT; P08679; -.
DR STRING; 4932.YCR005C; -.
DR ChEMBL; CHEMBL1741170; -.
DR iPTMnet; P08679; -.
DR MaxQB; P08679; -.
DR PaxDb; P08679; -.
DR PRIDE; P08679; -.
DR EnsemblFungi; YCR005C_mRNA; YCR005C; YCR005C.
DR GeneID; 850361; -.
DR KEGG; sce:YCR005C; -.
DR SGD; S000000598; CIT2.
DR VEuPathDB; FungiDB:YCR005C; -.
DR eggNOG; KOG2617; Eukaryota.
DR GeneTree; ENSGT00390000006813; -.
DR HOGENOM; CLU_022049_2_1_1; -.
DR InParanoid; P08679; -.
DR OMA; NCYPVLF; -.
DR BioCyc; YEAST:YCR005C-MON; -.
DR UniPathway; UPA00223; UER00717.
DR PRO; PR:P08679; -.
DR Proteomes; UP000002311; Chromosome III.
DR RNAct; P08679; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005777; C:peroxisome; IDA:SGD.
DR GO; GO:0004108; F:citrate (Si)-synthase activity; IDA:SGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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 Cytoplasm; Isopeptide bond; Peroxisome; Phosphoprotein; Reference proteome;
KW Transferase; Tricarboxylic acid cycle; Ubl conjugation.
FT CHAIN 1..460
FT /note="Citrate synthase, peroxisomal"
FT /id="PRO_0000169984"
FT MOTIF 458..460
FT /note="C-terminal peroxisome targeting signal (PTS1)"
FT /evidence="ECO:0000269|PubMed:2181273"
FT ACT_SITE 293
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT ACT_SITE 339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT ACT_SITE 394
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10117"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CROSSLNK 218
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 239
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 354
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT CROSSLNK 385
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:12872131"
FT MUTAGEN 293
FT /note="H->G: Prevents the stabilization of the enzyme by
FT oxaloacetate and impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:25982115"
FT MUTAGEN 294
FT /note="G->A,V: Leads to a decrease of the catalytic
FT activity and the ubiquitination efficiency."
FT /evidence="ECO:0000269|PubMed:25982115"
FT MUTAGEN 339
FT /note="H->Q,N: Prevents the stabilization of the enzyme by
FT oxaloacetate and impairs the catalytic activity."
FT /evidence="ECO:0000269|PubMed:25982115"
SQ SEQUENCE 460 AA; 51413 MW; AB2F66AD9A9399EF CRC64;
MTVPYLNSNR NVASYLQSNS SQEKTLKERF SEIYPIHAQD VRQFVKEHGK TKISDVLLEQ
VYGGMRGIPG SVWEGSVLDP EDGIRFRGRT IADIQKDLPK AKGSSQPLPE ALFWLLLTGE
VPTQAQVENL SADLMSRSEL PSHVVQLLDN LPKDLHPMAQ FSIAVTALES ESKFAKAYAQ
GISKQDYWSY TFEDSLDLLG KLPVIAAKIY RNVFKDGKMG EVDPNADYAK NLVNLIGSKD
EDFVDLMRLY LTIHSDHEGG NVSAHTSHLV GSALSSPYLS LASGLNGLAG PLHGRANQEV
LEWLFALKEE VNDDYSKDTI EKYLWDTLNS GRVIPGYGHA VLRKTDPRYM AQRKFAMDHF
PDYELFKLVS SIYEVAPGVL TEHGKTKNPW PNVDAHSGVL LQYYGLKESS FYTVLFGVSR
AFGILAQLIT DRAIGASIER PKSYSTEKYK ELVKNIESKL
