PYRD_SCHPO
ID PYRD_SCHPO Reviewed; 443 AA.
AC P32747;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE Short=DHOD;
DE Short=DHODase;
DE Short=DHOdehase;
DE EC=1.3.5.2;
DE AltName: Full=Dihydroorotate oxidase;
DE Flags: Precursor;
GN Name=ura3; ORFNames=SPAC57A10.12c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION, AND BIOPHYSICOCHEMICAL 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 [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
CC -!- FUNCTION: In the de novo pyrimidine biosynthesis pathway, catalyzes the
CC stereospecific oxidation of (S)-dihydroorotate to orotate with
CC reduction of flavin and the transfer of electrons to ubiquinone, which
CC is part of the repiratory chain. Does not use fumarate and NAD as
CC electron acceptors. {ECO:0000269|PubMed:1409592,
CC ECO:0000269|PubMed:15014982, ECO:0000269|PubMed:15196933}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + a quinone = a quinol + orotate;
CC Xref=Rhea:RHEA:30187, ChEBI:CHEBI:24646, ChEBI:CHEBI:30839,
CC ChEBI:CHEBI:30864, ChEBI:CHEBI:132124; EC=1.3.5.2;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Note=Binds 1 FMN per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=257 uM for (S)-dihydroorotate {ECO:0000269|PubMed:15196933};
CC KM=109 uM for decylubiquinone {ECO:0000269|PubMed:15196933};
CC Vmax=2 umol/min/mg enzyme {ECO:0000269|PubMed:15196933};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC orotate from (S)-dihydroorotate (quinone route): step 1/1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; X65114; CAA46230.1; -; mRNA.
DR EMBL; CU329670; CAB08175.1; -; Genomic_DNA.
DR PIR; A46248; A46248.
DR RefSeq; NP_593317.1; NM_001018748.2.
DR AlphaFoldDB; P32747; -.
DR SMR; P32747; -.
DR BioGRID; 279230; 46.
DR STRING; 4896.SPAC57A10.12c.1; -.
DR iPTMnet; P32747; -.
DR SwissPalm; P32747; -.
DR MaxQB; P32747; -.
DR PaxDb; P32747; -.
DR PRIDE; P32747; -.
DR EnsemblFungi; SPAC57A10.12c.1; SPAC57A10.12c.1:pep; SPAC57A10.12c.
DR GeneID; 2542781; -.
DR KEGG; spo:SPAC57A10.12c; -.
DR PomBase; SPAC57A10.12c; ura3.
DR VEuPathDB; FungiDB:SPAC57A10.12c; -.
DR eggNOG; KOG1436; Eukaryota.
DR HOGENOM; CLU_013640_4_3_1; -.
DR InParanoid; P32747; -.
DR OMA; ERIKMGA; -.
DR PhylomeDB; P32747; -.
DR Reactome; R-SPO-500753; Pyrimidine biosynthesis.
DR SABIO-RK; P32747; -.
DR UniPathway; UPA00070; UER00946.
DR PRO; PR:P32747; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:PomBase.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IDA:PomBase.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IDA:PomBase.
DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthetic process; IBA:GO_Central.
DR CDD; cd04738; DHOD_2_like; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005720; Dihydroorotate_DH.
DR InterPro; IPR005719; Dihydroorotate_DH_2.
DR InterPro; IPR001295; Dihydroorotate_DH_CS.
DR Pfam; PF01180; DHO_dh; 1.
DR TIGRFAMs; TIGR01036; pyrD_sub2; 1.
DR PROSITE; PS00911; DHODEHASE_1; 1.
DR PROSITE; PS00912; DHODEHASE_2; 1.
PE 1: Evidence at protein level;
KW Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Phosphoprotein; Pyrimidine biosynthesis;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 22..443
FT /note="Dihydroorotate dehydrogenase (quinone),
FT mitochondrial"
FT /id="PRO_0000029896"
FT TRANSMEM 38..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 267
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 122..126
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 171..175
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 234
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 264..269
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 306
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 335..336
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 358
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 387
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 408..409
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
SQ SEQUENCE 443 AA; 48296 MW; F58AB452E3A2F0D5 CRC64;
MYQRSLFRGV AQGLKRSSVR FQSTSSGSSN GNFFLRHWKL LSVIGSFTAG VAIYDMSDVR
SFIHGRIEMP LFHAFTTPEF SHRVAILAAS WGITPKDRVA DDPSLAVEVW GKKFCNPIGL
AAGFDKQADA ISGLLNFGFS YLEIGSVTPK PQPGNPKPRY FRLKPDLSVI NRYGFNSIGH
DAILAKIQKR VRKYIAKTSP QLLKQFDANP ASCTDPAVLG VPRSLIPNKF LGINLGKNKN
GNEIEDYVEG VRTFGNFADI LVINVSSPNT PGLRNLQKKS ALSTLLTAVV SERNKLNSPH
PPVLVKIAPD LNEEELTDIA DVLKKCKIDG VIVGNTTVQR PKTLKSTSHV EETGGLSGPP
LKPIALNTLR TLRKHLSSDI PIIGCGGISS GKDAIEYARA GATMVQVYTA LGYDGPVIAH
KIKQEILAEL KGKRWVDIIG KEE
