Reviewed, UniProtKB/Swiss-Prot P28272 (PYRD_YEAST)

Names and origin

Protein names

Recommended name:
    Dihydroorotate dehydrogenase
      Short name=DHOdehase
      Short name=DHODase
      Short name=DHOD
    EC=1.3.3.1
Alternative name(s):
    Dihydroorotate oxidase

Gene names

Name:	URA1
Ordered Locus Names:	YKL216W

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	In the de novo pyrimidine biosynthesic pathway, catalyzes the stereospecific oxidation of (S)-dihydroorotate to orotate and the reduction of fumarate to succinate. Does not use oxaloacetate and NAD or NADP as electron acceptors. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10
Catalytic activity	(S)-dihydroorotate + O2 = orotate + H2O2.
Cofactor	Binds 1 FMN per subunit. Ref.6
Enzyme regulation	The activity is independent of the presence of oxygen.
Pathway	Pyrimidine metabolism; UMP biosynthesis via de novo pathway; orotate from (S)-dihydroorotate (O2 route): step 1/1.
Subunit structure	Homodimer. Ref.6
Subcellular location	Cytoplasm.
Miscellaneous	Present with 264000 molecules/cell in log phase SD medium. Ref.7
Sequence similarities	Belongs to the dihydroorotate dehydrogenase family. Type 1 subfamily.
Biophysicochemical properties	Kinetic parameters: KM=8.4 µM for (S)-dihydroorotate (at pH 7.5) KM=45 µM for fumarate (at pH 7.5) KM=115 µM for 2,6-dichloroindophenol Vmax=20.4 µmol/min/mg enzyme (with 2,6-dichloroindophenol as electron acceptor) Vmax=5.1 µmol/min/mg enzyme (with fumarate as electron acceptor) pH dependence: Optimum pH is 8.5. Active from pH 7 to pH 10.

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Cytoplasm
Ligand	FMN Flavoprotein
Molecular function	Oxidoreductase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	'de novo' pyrimidine base biosynthetic process Inferred from mutant phenotype. Source: SGD UMP biosynthetic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.5 Inferred from direct assay. Source: SGD extrinsic to membrane Inferred from direct assay. Source: SGD
Molecular function	dihydroorotate oxidase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHO4	Q00246	1	EBI-14386,EBI-15144

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 314	314	Dihydroorotate dehydrogenase		PRO_0000148506
Sites
	Active site	133	1	Nucleophile By similarity
Natural variations
	Natural variant	58	1	E → K in strain: CLIB 95, CLIB 219, CLIB 382, CLIB 388, CLIB 413, CLIB 556, CLIB 630, K1, R12, R13, YIIc12 and YIIc17. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P28272-1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 0F1FF9BDA7F8D68E	FASTA	314	34,801
	10 20 30 40 50 60 MTASLTTKFL NNTYENPFMN ASGVHCMTTQ ELDELANSKA GAFITKSATT LEREGNPEPR 70 80 90 100 110 120 YISVPLGSIN SMGLPNEGID YYLSYVLNRQ KNYPDAPAIF FSVAGMSIDE NLNLLRKIQD 130 140 150 160 170 180 SEFNGITELN LSCPNVPGKP QVAYDFDLTK ETLEKVFAFF KKPLGVKLPP YFDFAHFDIM 190 200 210 220 230 240 AKILNEFPLA YVNSINSIGN GLFIDVEKES VVVKPKNGFG GIGGEYVKPT ALANVRAFYT 250 260 270 280 290 300 RLRPEIKVIG TGGIKSGKDA FEHLLCGASM LQIGTELQKE GVKIFERIEK ELKDIMEAKG 310 YTSIDQFRGK LNSI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae." Roy A. Gene 118:149-150(1992) [PubMed: 1511880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION. Strain: ATCC 28383 / FL100 / VTT C-80102.
[2]	"Differential evolution of the Saccharomyces cerevisiae DUP240 paralogs and implication of recombination in phylogeny." Leh-Louis V., Wirth B., Despons L., Wain-Hobson S., Potier S., Souciet J.-L. Nucleic Acids Res. 32:2069-2078(2004) [PubMed: 15087486] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-58. Strain: CLIB 219, CLIB 382, CLIB 388, CLIB 410, CLIB 413, CLIB 556, CLIB 630, CLIB 95, K1, R12, R13, Sigma 1278B, YIIc12 and YIIc17.
[3]	"The complete sequencing of a 24.6 kb segment of yeast chromosome XI identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open reading frames including homologues to the threonine dehydratases, membrane transporters, hydantoinases and the phospholipase A2-activating protein." Tzermia M., Horaitis O., Alexandraki D. Yeast 10:663-679(1994) [PubMed: 7941750] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"Complete DNA sequence of yeast chromosome XI." Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C. , Domdey H., Duesterhoeft A., Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., Becker I., Mewes H.-W. Nature 369:371-378(1994) [PubMed: 8196765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts." Nagy M., Lacroute F., Thomas D. Proc. Natl. Acad. Sci. U.S.A. 89:8966-8970(1992) [PubMed: 1409592] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Catalytic properties of dihydroorotate dehydrogenase from Saccharomyces cerevisiae: studies on pH, alternate substrates, and inhibitors." Jordan D.B., Bisaha J.J., Picollelli M.A. Arch. Biochem. Biophys. 378:84-92(2000) [PubMed: 10871048] [Abstract] Cited for: FUNCTION, SUBUNIT, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
[7]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[8]	"Two different dihydroorotate dehydrogenases from yeast Saccharomyces kluyveri." Zameitat E., Knecht W., Piskur J., Loeffler M. FEBS Lett. 568:129-134(2004) [PubMed: 15196933] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]	"Horizontal gene transfer promoted evolution of the ability to propagate under anaerobic conditions in yeasts." Gojkovic Z., Knecht W., Zameitat E., Warneboldt J., Coutelis J.-B., Pynyaha Y., Neuveglise C., Moeller K., Loeffler M., Piskur J. Mol. Genet. Genomics 271:387-393(2004) [PubMed: 15014982] [Abstract] Cited for: FUNCTION.
[10]	"Dihydroorotate dehydrogenase from Saccharomyces cerevisiae: spectroscopic investigations with the recombinant enzyme throw light on catalytic properties and metabolism of fumarate analogues." Zameitat E., Pierik A.J., Zocher K., Loeffler M. FEMS Yeast Res. 7:897-904(2007) [PubMed: 17617217] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M83295 Genomic DNA. Translation: AAA34566.1. X59371 Genomic DNA. Translation: CAA42014.1. AJ585637 Genomic DNA. Translation: CAE52157.1. AJ585638 Genomic DNA. Translation: CAE52158.1. AJ585639 Genomic DNA. Translation: CAE52159.1. AJ585640 Genomic DNA. Translation: CAE52160.1. AJ585641 Genomic DNA. Translation: CAE52161.1. AJ585642 Genomic DNA. Translation: CAE52162.1. AJ585643 Genomic DNA. Translation: CAE52163.1. AJ585644 Genomic DNA. Translation: CAE52164.1. AJ585645 Genomic DNA. Translation: CAE52165.1. AJ585646 Genomic DNA. Translation: CAE52166.1. AJ585647 Genomic DNA. Translation: CAE52167.1. AJ585648 Genomic DNA. Translation: CAE52168.1. AJ585649 Genomic DNA. Translation: CAE52169.1. AJ585650 Genomic DNA. Translation: CAE52170.1. AJ585651 Genomic DNA. Translation: CAE52171.1. X75951 Genomic DNA. Translation: CAA53557.1. Z28216 Genomic DNA. Translation: CAA82061.1.
PIR	JC1276.
RefSeq	NP_012706.1.
3D structure databases
SMR	P28272. Positions 5-314.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:6573N.
IntAct	P28272. 2 interactions.
STRING	P28272.
Proteomic databases
PeptideAtlas	P28272.
PRIDE	P28272.
Genome annotation databases
Ensembl	YKL216W; YKL216W; YKL216W; Saccharomyces cerevisiae. [Genome view]
GeneID	853664.
KEGG	sce:YKL216W.
NMPDR	fig|4932.3.peg.3684.
Organism-specific databases
CYGD	YKL216w.
SGD	S000001699. URA1.
Phylogenomic databases
HOGENOM	P28272.
OMA	KPLGVKL
OrthoDB	EOG9CNS7M
Enzyme and pathway databases
BioCyc	MetaCyc:YKL216W-MON.
BRENDA	1.3.3.1. 250.
Gene expression databases
ArrayExpress	P28272.
Genevestigator	P28272.
GermOnline	YKL216W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR013785. Aldolase_TIM. IPR012135. Dihydroorotate_DH_1_2. IPR005720. Dihydroorotate_DH_1_core. IPR001295. Dihydroorotate_DH_CS. [Graphical view]
Gene3D	G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.
Pfam	PF01180. DHO_dh. 1 hit. [Graphical view]
PIRSF	PIRSF000164. DHO_oxidase. 1 hit.
TIGRFAMs	TIGR01037. pyrD_sub1_fam. 1 hit.
PROSITE	PS00911. DHODEHASE_1. 1 hit. PS00912. DHODEHASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	974596.

Entry information

Entry name

PYRD_YEAST

Accession

Primary (citable) accession number: P28272
Secondary accession number(s): Q2XN75, Q70DC7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	November 24, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)