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 13-NOV-2019, entry version 184. 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; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3540614; DOI=10.1128/mcb.6.12.4509; RA Rosenkrantz M., Alam T., Kim K.-S., Clark B.J., Srere P.A., RA 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 RT chromosome 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., RA Fabre F., Fairhead C., Faye G., Feldmann H., Fiers W., RA Francingues-Gaillard M.-C., Franco L., Frontali L., Fukuhara H., RA Fuller L.J., Galland P., Gent M.E., Gigot D., Gilliquet V., RA Glansdorff N., Goffeau A., Grenson M., Grisanti P., Grivell L.A., RA de Haan M., Haasemann M., Hatat D., Hoenicka J., Hegemann J.H., RA Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P., Huse K., RA 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., RA Pohl F.M., Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., RA Remacha M.A., Richterich P., Roberts A.B., Rodriguez F., Sanz E., RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., RA Skala J., Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., RA Stateva L.I., Steensma H.Y., Steiner S., Thierry A., Thireos G., RA Tzermia M., Urrestarazu L.A., Valle G., Vetter I., RA van Vliet-Reedijk J.C., Voet M., Volckaert G., Vreken P., Wang H., RA Warmington J.R., von Wettstein D., Wicksteed B.L., Wilson C., RA Wurst H., Xu G., Yoshikawa A., Zimmermann F.K., 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., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT 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., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding 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; RA Liao X., Small W.C., Srere P.A., Butow R.A.; RT "Intramitochondrial functions regulate nonmitochondrial citrate RT synthase (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; RA Kim K.S., Rosenkrantz M.S., Guarente L.; RT "Saccharomyces cerevisiae contains two functional citrate synthase RT 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; RA Lewin A.S., Hines V., Small G.M.; RT "Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae RT is 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., 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 [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., RA Marsischky G., 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 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 [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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal 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; CC isocitrate from oxaloacetate: step 1/2. CC {ECO:0000269|PubMed:3023912}. CC -!- SUBUNIT: Interacts with F-box protein UCC1. CC {ECO:0000269|PubMed:25982115}. CC -!- INTERACTION: CC Self; NbExp=3; IntAct=EBI-4713, EBI-4713; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25982115}. CC Peroxisome {ECO:0000269|PubMed:2181273, CC ECO:0000269|PubMed:25982115}. CC -!- INDUCTION: Expression is repressed in medium containing both CC glucose and glutamate (PubMed:3023912). Expression is up-regulated CC by the 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 CC feedback loop that stabilizes CIT2 (PubMed:25982115). CC {ECO:0000269|PubMed:25982115}. CC -!- DISRUPTION PHENOTYPE: Leads to glutamate auxotrophy and poor CC growth on rich medium containing lactate, a nonfermentable carbon CC source, when CIT1 is also deleted. {ECO:0000269|PubMed:3023912}. CC -!- MISCELLANEOUS: Citrate synthase is found in nearly all cells CC capable of oxidative metabolism. {ECO:0000305}. CC -!- MISCELLANEOUS: Present with 2310 molecules/cell in log phase SD CC medium. {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 SMR; P08679; -. DR BioGrid; 30983; 112. 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 EuPathDB; FungiDB:YCR005C; -. DR SGD; S000000598; CIT2. DR HOGENOM; HOG000130831; -. DR InParanoid; P08679; -. DR KO; K01647; -. DR OMA; NCYPVLF; -. DR BioCyc; YEAST:YCR005C-MONOMER; -. DR UniPathway; UPA00223; UER00717. DR PRO; PR:P08679; -. DR Proteomes; UP000002311; Chromosome III. 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:0006537; P:glutamate biosynthetic process; TAS:SGD. DR GO; GO:0006097; P:glyoxylate cycle; TAS: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 Complete proteome; Cytoplasm; Isopeptide bond; Peroxisome; KW Phosphoprotein; Reference proteome; Transferase; KW Tricarboxylic acid cycle; Ubl conjugation. FT CHAIN 1 460 Citrate synthase, peroxisomal. FT /FTId=PRO_0000169984. FT MOTIF 458 460 C-terminal peroxisome targeting signal FT (PTS1). {ECO:0000269|PubMed:2181273}. FT ACT_SITE 293 293 {ECO:0000255|PROSITE-ProRule:PRU10117}. FT ACT_SITE 339 339 {ECO:0000255|PROSITE-ProRule:PRU10117}. FT ACT_SITE 394 394 {ECO:0000255|PROSITE-ProRule:PRU10117}. FT MOD_RES 21 21 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT CROSSLNK 218 218 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000244|PubMed:22106047}. FT CROSSLNK 239 239 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000244|PubMed:22106047}. FT CROSSLNK 354 354 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:12872131}. FT CROSSLNK 385 385 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:12872131}. FT MUTAGEN 293 293 H->G: Prevents the stabilization of the FT enzyme by oxaloacetate and impairs the FT catalytic activity. FT {ECO:0000269|PubMed:25982115}. FT MUTAGEN 294 294 G->A,V: Leads to a decrease of the FT catalytic activity and the ubiquitination FT efficiency. FT {ECO:0000269|PubMed:25982115}. FT MUTAGEN 339 339 H->Q,N: Prevents the stabilization of the FT enzyme by oxaloacetate and impairs the FT catalytic activity. FT {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 //