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 02-OCT-2024, entry version 207. 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:25982115, PubMed:3023912). Catalyzes the CC condensation of acetyl coenzyme A and oxaloacetate to form citrate CC (PubMed:25982115, PubMed:3023912). 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 PDB; 8GR8; X-ray; 2.39 A; A/B=1-460. DR PDB; 8GR9; X-ray; 1.48 A; A/B=1-460. DR PDB; 8GRE; X-ray; 2.30 A; A/B=1-460. DR PDB; 8GRF; X-ray; 2.53 A; A/B=1-460. DR PDBsum; 8GR8; -. DR PDBsum; 8GR9; -. DR PDBsum; 8GRE; -. DR PDBsum; 8GRF; -. DR AlphaFoldDB; P08679; -. DR SMR; P08679; -. DR BioGRID; 30983; 122. DR DIP; DIP-1259N; -. DR IntAct; P08679; 8. DR MINT; P08679; -. DR STRING; 4932.YCR005C; -. DR BindingDB; P08679; -. DR ChEMBL; CHEMBL1741170; -. DR iPTMnet; P08679; -. DR PaxDb; 4932-YCR005C; -. DR PeptideAtlas; P08679; -. DR EnsemblFungi; YCR005C_mRNA; YCR005C; YCR005C. DR GeneID; 850361; -. DR KEGG; sce:YCR005C; -. DR AGR; SGD:S000000598; -. 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; HDSHFAK; -. DR OrthoDB; 3513214at2759; -. DR BioCyc; YEAST:YCR005C-MONOMER; -. DR UniPathway; UPA00223; UER00717. DR BioGRID-ORCS; 850361; 1 hit in 10 CRISPR screens. 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; 1.10.580.10; Citrate Synthase, domain 1; 1. DR Gene3D; 1.10.230.10; Cytochrome P450-Terp, domain 2; 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 NCBIfam; TIGR01793; cit_synth_euk; 1. DR PANTHER; PTHR11739; CITRATE SYNTHASE; 1. DR PANTHER; PTHR11739:SF8; CITRATE SYNTHASE, MITOCHONDRIAL; 1. DR Pfam; PF00285; Citrate_synt; 1. DR PRINTS; PR00143; CITRTSNTHASE. DR SUPFAM; SSF48256; Citrate synthase; 1. DR PROSITE; PS00480; CITRATE_SYNTHASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Isopeptide bond; Peroxisome; Phosphoprotein; KW Reference proteome; 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" FT HELIX 26..48 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 51..57 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 58..61 FT /evidence="ECO:0007829|PDB:8GR9" FT TURN 62..67 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 74..79 FT /evidence="ECO:0007829|PDB:8GR9" FT TURN 80..82 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 83..86 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 91..97 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 109..118 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 124..136 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 142..150 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 157..167 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 168..171 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 173..180 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 187..214 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 228..236 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 241..253 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 262..272 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 277..288 FT /evidence="ECO:0007829|PDB:8GR9" FT TURN 291..295 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 296..309 FT /evidence="ECO:0007829|PDB:8GR9" FT TURN 311..313 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 317..329 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 337..341 FT /evidence="ECO:0007829|PDB:8GRE" FT HELIX 347..359 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 364..373 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 376..383 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 387..391 FT /evidence="ECO:0007829|PDB:8GRE" FT HELIX 394..403 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 409..411 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 412..434 FT /evidence="ECO:0007829|PDB:8GR9" FT STRAND 442..444 FT /evidence="ECO:0007829|PDB:8GR9" FT HELIX 446..458 FT /evidence="ECO:0007829|PDB:8GR9" 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 //