PYRD_DROME
ID PYRD_DROME Reviewed; 405 AA.
AC P32748; Q8INQ4; Q8INQ5; Q9VHP2;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE Short=DHOdehase;
DE Short=Dihydroorotate oxidase;
DE EC=1.3.5.2;
DE Flags: Precursor;
GN Name=Dhod; ORFNames=CG9741;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8444342; DOI=10.1016/0378-1119(93)90393-h;
RA Rawls J., Kirkpatrick R., Yang J., Lacy L.;
RT "The dhod gene and deduced structure of mitochondrial dihydroorotate
RT dehydrogenase in Drosophila melanogaster.";
RL Gene 124:191-197(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 325-405.
RX PubMed=2482933; DOI=10.1007/bf00259612;
RA Jones W.K., Kirkpatrick R., Rawls J.M.;
RT "Molecular cloning and transcript mapping of the dihydroorotate
RT dehydrogenase dhod locus of Drosophila melanogaster.";
RL Mol. Gen. Genet. 219:397-403(1989).
CC -!- FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with
CC quinone as electron acceptor. {ECO:0000250}.
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; Evidence={ECO:0000250};
CC Note=Binds 1 FMN per subunit. {ECO:0000250};
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB59185.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ22565.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA35184.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L00964; AAB59185.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AE014297; AAF54260.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13391.2; -; Genomic_DNA.
DR EMBL; BT009968; AAQ22437.1; -; mRNA.
DR EMBL; BT010096; AAQ22565.1; ALT_INIT; mRNA.
DR EMBL; X17297; CAA35184.1; ALT_FRAME; mRNA.
DR PIR; JN0500; JN0500.
DR PIR; S15742; S15742.
DR RefSeq; NP_477224.1; NM_057876.5.
DR RefSeq; NP_599138.3; NM_134311.3.
DR AlphaFoldDB; P32748; -.
DR SMR; P32748; -.
DR BioGRID; 66198; 2.
DR DIP; DIP-23907N; -.
DR IntAct; P32748; 2.
DR STRING; 7227.FBpp0289671; -.
DR PaxDb; P32748; -.
DR PRIDE; P32748; -.
DR DNASU; 41022; -.
DR EnsemblMetazoa; FBtr0081890; FBpp0081376; FBgn0000447.
DR EnsemblMetazoa; FBtr0300442; FBpp0289671; FBgn0000447.
DR GeneID; 41022; -.
DR KEGG; dme:Dmel_CG9741; -.
DR CTD; 41022; -.
DR FlyBase; FBgn0000447; Dhod.
DR VEuPathDB; VectorBase:FBgn0000447; -.
DR eggNOG; KOG1436; Eukaryota.
DR GeneTree; ENSGT00500000044924; -.
DR HOGENOM; CLU_013640_0_0_1; -.
DR InParanoid; P32748; -.
DR OMA; ERIKMGA; -.
DR OrthoDB; 1194348at2759; -.
DR PhylomeDB; P32748; -.
DR Reactome; R-DME-500753; Pyrimidine biosynthesis.
DR SignaLink; P32748; -.
DR UniPathway; UPA00070; UER00946.
DR BioGRID-ORCS; 41022; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41022; -.
DR PRO; PR:P32748; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0000447; Expressed in eye disc (Drosophila) and 25 other tissues.
DR Genevisible; P32748; DM.
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:0005758; C:mitochondrial intermembrane space; IDA:FlyBase.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IDA:FlyBase.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; ISS:FlyBase.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Pyrimidine biosynthesis; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..405
FT /note="Dihydroorotate dehydrogenase (quinone),
FT mitochondrial"
FT /id="PRO_0000029887"
FT TOPO_DOM ?..20
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT TRANSMEM 21..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..401
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT ACT_SITE 218
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 103..107
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 152..156
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 215..220
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 289..290
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 311
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 340
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 361..362
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
SQ SEQUENCE 405 AA; 44342 MW; 875F32BBED8BCC9D CRC64;
MDQDHLKNAK NATRRVGRLR SLGIVTVGGA ALVAGITAYK NQDQLFRTFV MPAVRLLPAE
ASHQLAVLAC KYRLCPVSQY HDDQNLHTSF FGRMLSNPIG IAAGFDKNAE AVDGLQDLGF
GFIEVGTVTP AAQEGNPKPR VFRLTEDKAI INRYGFNSDG HQAVLQRLRL LRKKENFNGV
VGVNLGRNKT TMSPIADYVQ GVRVFGPVAD YLVINVSSPN TKGLRDMQSK EKLRELLEQV
NDTKSSLDKN KNVPILLKLS PDLSLDDMKD IVWVIKRKKS RVDGLIVSNT TVSRENIEKN
KLAEETGGLS GPPLKARSTE MIAQMYQLTD GKIPIIGVGG VASGYDAYEK IEAGASYVQI
YTALVYEGPA LVEDIKAELS ALITRLGHTN VADVVGTNSK FYLPK
