PYRD_YEAST
ID PYRD_YEAST Reviewed; 314 AA.
AC P28272; D6VWY7; Q2XN75; Q70DC7;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Dihydroorotate dehydrogenase (fumarate);
DE Short=DHOD;
DE Short=DHODase;
DE Short=DHOdehase;
DE EC=1.3.98.1;
DE AltName: Full=Dihydroorotate oxidase;
GN Name=URA1; OrderedLocusNames=YKL216W;
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], AND FUNCTION.
RC STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RX PubMed=1511880; DOI=10.1016/0378-1119(92)90265-q;
RA Roy A.;
RT "Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae.";
RL Gene 118:149-150(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-58.
RC STRAIN=CLIB 219, CLIB 382, CLIB 388, CLIB 410, CLIB 413, CLIB 556,
RC CLIB 630, CLIB 95, K1, R12, R13, Sigma 1278B, YIIc12, and YIIc17;
RX PubMed=15087486; DOI=10.1093/nar/gkh529;
RA Leh-Louis V., Wirth B., Despons L., Wain-Hobson S., Potier S.,
RA Souciet J.-L.;
RT "Differential evolution of the Saccharomyces cerevisiae DUP240 paralogs and
RT implication of recombination in phylogeny.";
RL Nucleic Acids Res. 32:2069-2078(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7941750; DOI=10.1002/yea.320100511;
RA Tzermia M., Horaitis O., Alexandraki D.;
RT "The complete sequencing of a 24.6 kb segment of yeast chromosome XI
RT identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open
RT reading frames including homologues to the threonine dehydratases, membrane
RT transporters, hydantoinases and the phospholipase A2-activating protein.";
RL Yeast 10:663-679(1994).
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1409592; DOI=10.1073/pnas.89.19.8966;
RA Nagy M., Lacroute F., Thomas D.;
RT "Divergent evolution of pyrimidine biosynthesis between anaerobic and
RT aerobic yeasts.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8966-8970(1992).
RN [7]
RP FUNCTION, SUBUNIT, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10871048; DOI=10.1006/abbi.2000.1823;
RA Jordan D.B., Bisaha J.J., Picollelli M.A.;
RT "Catalytic properties of dihydroorotate dehydrogenase from Saccharomyces
RT cerevisiae: studies on pH, alternate substrates, and inhibitors.";
RL Arch. Biochem. Biophys. 378:84-92(2000).
RN [8]
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=15196933; DOI=10.1016/j.febslet.2004.05.017;
RA Zameitat E., Knecht W., Piskur J., Loeffler M.;
RT "Two different dihydroorotate dehydrogenases from yeast Saccharomyces
RT kluyveri.";
RL FEBS Lett. 568:129-134(2004).
RN [10]
RP FUNCTION.
RX PubMed=15014982; DOI=10.1007/s00438-004-0995-7;
RA Gojkovic Z., Knecht W., Zameitat E., Warneboldt J., Coutelis J.-B.,
RA Pynyaha Y., Neuveglise C., Moeller K., Loeffler M., Piskur J.;
RT "Horizontal gene transfer promoted evolution of the ability to propagate
RT under anaerobic conditions in yeasts.";
RL Mol. Genet. Genomics 271:387-393(2004).
RN [11]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17617217; DOI=10.1111/j.1567-1364.2007.00275.x;
RA Zameitat E., Pierik A.J., Zocher K., Loeffler M.;
RT "Dihydroorotate dehydrogenase from Saccharomyces cerevisiae: spectroscopic
RT investigations with the recombinant enzyme throw light on catalytic
RT properties and metabolism of fumarate analogues.";
RL FEMS Yeast Res. 7:897-904(2007).
RN [12]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-46, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with
CC fumarate as the electron acceptor. Molecular oxygen can replace
CC fumarate in vitro. Does not use oxaloacetate or NAD or NADP as electron
CC acceptors. {ECO:0000269|PubMed:10871048, ECO:0000269|PubMed:1409592,
CC ECO:0000269|PubMed:15014982, ECO:0000269|PubMed:1511880,
CC ECO:0000269|PubMed:15196933, ECO:0000269|PubMed:17617217}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + fumarate = orotate + succinate;
CC Xref=Rhea:RHEA:30059, ChEBI:CHEBI:29806, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:30839, ChEBI:CHEBI:30864; EC=1.3.98.1;
CC Evidence={ECO:0000269|PubMed:15196933};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:10871048};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:10871048};
CC -!- ACTIVITY REGULATION: The activity is independent of the presence of
CC oxygen.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.4 uM for (S)-dihydroorotate (at pH 7.5)
CC {ECO:0000269|PubMed:10871048, ECO:0000269|PubMed:15196933,
CC ECO:0000269|PubMed:17617217};
CC KM=45 uM for fumarate (at pH 7.5) {ECO:0000269|PubMed:10871048,
CC ECO:0000269|PubMed:15196933, ECO:0000269|PubMed:17617217};
CC KM=115 uM for 2,6-dichloroindophenol {ECO:0000269|PubMed:10871048,
CC ECO:0000269|PubMed:15196933, ECO:0000269|PubMed:17617217};
CC Vmax=20.4 umol/min/mg enzyme (with 2,6-dichloroindophenol as electron
CC acceptor) {ECO:0000269|PubMed:10871048, ECO:0000269|PubMed:15196933,
CC ECO:0000269|PubMed:17617217};
CC Vmax=5.1 umol/min/mg enzyme (with fumarate as electron acceptor)
CC {ECO:0000269|PubMed:10871048, ECO:0000269|PubMed:15196933,
CC ECO:0000269|PubMed:17617217};
CC pH dependence:
CC Optimum pH is 8.5. Active from pH 7 to pH 10.
CC {ECO:0000269|PubMed:10871048, ECO:0000269|PubMed:15196933,
CC ECO:0000269|PubMed:17617217};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10871048}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1409592}.
CC -!- MISCELLANEOUS: Present with 264000 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; M83295; AAA34566.1; -; Genomic_DNA.
DR EMBL; X59371; CAA42014.1; -; Genomic_DNA.
DR EMBL; AJ585637; CAE52157.1; -; Genomic_DNA.
DR EMBL; AJ585638; CAE52158.1; -; Genomic_DNA.
DR EMBL; AJ585639; CAE52159.1; -; Genomic_DNA.
DR EMBL; AJ585640; CAE52160.1; -; Genomic_DNA.
DR EMBL; AJ585641; CAE52161.1; -; Genomic_DNA.
DR EMBL; AJ585642; CAE52162.1; -; Genomic_DNA.
DR EMBL; AJ585643; CAE52163.1; -; Genomic_DNA.
DR EMBL; AJ585644; CAE52164.1; -; Genomic_DNA.
DR EMBL; AJ585645; CAE52165.1; -; Genomic_DNA.
DR EMBL; AJ585646; CAE52166.1; -; Genomic_DNA.
DR EMBL; AJ585647; CAE52167.1; -; Genomic_DNA.
DR EMBL; AJ585648; CAE52168.1; -; Genomic_DNA.
DR EMBL; AJ585649; CAE52169.1; -; Genomic_DNA.
DR EMBL; AJ585650; CAE52170.1; -; Genomic_DNA.
DR EMBL; AJ585651; CAE52171.1; -; Genomic_DNA.
DR EMBL; X75951; CAA53557.1; -; Genomic_DNA.
DR EMBL; Z28216; CAA82061.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA08953.1; -; Genomic_DNA.
DR PIR; JC1276; JC1276.
DR RefSeq; NP_012706.1; NM_001179781.1.
DR AlphaFoldDB; P28272; -.
DR SMR; P28272; -.
DR BioGRID; 33949; 108.
DR DIP; DIP-6573N; -.
DR IntAct; P28272; 4.
DR MINT; P28272; -.
DR STRING; 4932.YKL216W; -.
DR BindingDB; P28272; -.
DR ChEMBL; CHEMBL5621; -.
DR iPTMnet; P28272; -.
DR MaxQB; P28272; -.
DR PaxDb; P28272; -.
DR PRIDE; P28272; -.
DR EnsemblFungi; YKL216W_mRNA; YKL216W; YKL216W.
DR GeneID; 853664; -.
DR KEGG; sce:YKL216W; -.
DR SGD; S000001699; URA1.
DR VEuPathDB; FungiDB:YKL216W; -.
DR eggNOG; KOG1436; Eukaryota.
DR GeneTree; ENSGT00500000044896; -.
DR HOGENOM; CLU_042042_3_0_1; -.
DR InParanoid; P28272; -.
DR OMA; SCPHAKG; -.
DR BioCyc; MetaCyc:YKL216W-MON; -.
DR BioCyc; YEAST:YKL216W-MON; -.
DR SABIO-RK; P28272; -.
DR UniPathway; UPA00070; -.
DR PRO; PR:P28272; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P28272; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:SGD.
DR GO; GO:1990663; F:dihydroorotate dehydrogenase (fumarate) activity; IEA:UniProtKB-EC.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IDA:SGD.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IDA:SGD.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd04741; DHOD_1A_like; 1.
DR Gene3D; 2.30.26.10; -; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00224; DHO_dh_type1; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR033886; DHOD_1A.
DR InterPro; IPR023359; Dihydro_DH_chainA_dom2.
DR InterPro; IPR005720; Dihydroorotate_DH.
DR InterPro; IPR024920; Dihydroorotate_DH_1.
DR InterPro; IPR012135; Dihydroorotate_DH_1_2.
DR InterPro; IPR001295; Dihydroorotate_DH_CS.
DR Pfam; PF01180; DHO_dh; 1.
DR PIRSF; PIRSF000164; DHO_oxidase; 1.
DR TIGRFAMs; TIGR01037; pyrD_sub1_fam; 1.
DR PROSITE; PS00911; DHODEHASE_1; 1.
DR PROSITE; PS00912; DHODEHASE_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Flavoprotein; FMN; Isopeptide bond; Oxidoreductase;
KW Pyrimidine biosynthesis; Reference proteome; Ubl conjugation.
FT CHAIN 1..314
FT /note="Dihydroorotate dehydrogenase (fumarate)"
FT /id="PRO_0000148506"
FT ACT_SITE 133
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 46..47
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 46
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 70..74
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 195
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 196..197
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 224
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 252..253
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 274..275
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT CROSSLNK 46
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT VARIANT 58
FT /note="E -> K (in strain: CLIB 95, CLIB 219, CLIB 382, CLIB
FT 388, CLIB 413, CLIB 556, CLIB 630, K1, R12, R13, YIIc12 and
FT YIIc17)"
FT /evidence="ECO:0000269|PubMed:15087486"
SQ SEQUENCE 314 AA; 34801 MW; 0F1FF9BDA7F8D68E CRC64;
MTASLTTKFL NNTYENPFMN ASGVHCMTTQ ELDELANSKA GAFITKSATT LEREGNPEPR
YISVPLGSIN SMGLPNEGID YYLSYVLNRQ KNYPDAPAIF FSVAGMSIDE NLNLLRKIQD
SEFNGITELN LSCPNVPGKP QVAYDFDLTK ETLEKVFAFF KKPLGVKLPP YFDFAHFDIM
AKILNEFPLA YVNSINSIGN GLFIDVEKES VVVKPKNGFG GIGGEYVKPT ALANVRAFYT
RLRPEIKVIG TGGIKSGKDA FEHLLCGASM LQIGTELQKE GVKIFERIEK ELKDIMEAKG
YTSIDQFRGK LNSI
