ID   PYRD_BOVIN              Reviewed;         395 AA.
AC   Q5E9W3; Q0P590;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 1.
DT   27-MAR-2024, entry version 101.
DE   RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE            Short=DHOdehase;
DE            EC=1.3.5.2 {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
DE   AltName: Full=Dihydroorotate oxidase;
DE   Flags: Precursor;
GN   Name=DHODH;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=3733756; DOI=10.1016/s0021-9258(18)67396-x;
RA   Hines V., Keys L.D. III, Johnston M.;
RT   "Purification and properties of the bovine liver mitochondrial
RT   dihydroorotate dehydrogenase.";
RL   J. Biol. Chem. 261:11386-11392(1986).
RN   [4]
RP   ERRATUM OF PUBMED:3733756.
RA   Hines V., Keys L.D. III, Johnston M.;
RL   J. Biol. Chem. 262:15322-15322(1987).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME
RP   KINETICS.
RX   PubMed=2540819; DOI=10.1021/bi00429a040;
RA   Hines V., Johnston M.;
RT   "Analysis of the kinetic mechanism of the bovine liver mitochondrial
RT   dihydroorotate dehydrogenase.";
RL   Biochemistry 28:1222-1226(1989).
CC   -!- FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with
CC       quinone as electron acceptor. Required for UMP biosynthesis via de novo
CC       pathway. {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756}.
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         Evidence={ECO:0000269|PubMed:3733756};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000250|UniProtKB:Q02127};
CC       Note=Binds 1 FMN per subunit. {ECO:0000250|UniProtKB:Q02127};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=9.2 uM for (S)-dihydroorotate {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC         KM=13.6 uM for benzyl-(S)-dihydroorotate {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC         KM=19.4 uM for methyl-(S)-dihydroorotate {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC         KM=10.8 uM for quinone Q(6) {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC         KM=13.2 uM for quinone Q(7) {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC         Vmax=72 umol/min/mg enzyme toward (S)-dihydroorotate
CC         {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
CC         Vmax=80 umol/min/mg enzyme toward benzyl-(S)-dihydroorotate
CC         {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
CC         Vmax=63 umol/min/mg enzyme toward methyl-(S)-dihydroorotate
CC         {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
CC         Vmax=82 umol/min/mg enzyme toward quinone Q(6)
CC         {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
CC         Vmax=88 umol/min/mg enzyme toward quinone Q(7)
CC         {ECO:0000269|PubMed:2540819, ECO:0000269|PubMed:3733756};
CC       pH dependence:
CC         Optimum pH is 8.0. {ECO:0000269|PubMed:2540819,
CC         ECO:0000269|PubMed:3733756};
CC   -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC       orotate from (S)-dihydroorotate (quinone route): step 1/1.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q02127}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:Q02127}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q02127}.
CC   -!- PTM: The uncleaved transit peptide is required for mitochondrial
CC       targeting and proper membrane integration. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC       subfamily. {ECO:0000305}.
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DR   EMBL; BT020807; AAX08824.1; -; mRNA.
DR   EMBL; BC120337; AAI20338.1; -; mRNA.
DR   RefSeq; NP_001015650.1; NM_001015650.1.
DR   AlphaFoldDB; Q5E9W3; -.
DR   SMR; Q5E9W3; -.
DR   STRING; 9913.ENSBTAP00000026495; -.
DR   PaxDb; 9913-ENSBTAP00000055859; -.
DR   GeneID; 533873; -.
DR   KEGG; bta:533873; -.
DR   CTD; 1723; -.
DR   eggNOG; KOG1436; Eukaryota.
DR   InParanoid; Q5E9W3; -.
DR   OrthoDB; 313431at2759; -.
DR   SABIO-RK; Q5E9W3; -.
DR   UniPathway; UPA00070; UER00946.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR   GO; GO:0106430; F:dihydroorotate dehydrogenase (quinone) activity; IEA:UniProtKB-EC.
DR   GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
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; Aldolase class I; 1.
DR   HAMAP; MF_00225; DHO_dh_type2; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR005719; Dihydroorotate_DH_2.
DR   InterPro; IPR005720; Dihydroorotate_DH_cat.
DR   InterPro; IPR001295; Dihydroorotate_DH_CS.
DR   NCBIfam; TIGR01036; pyrD_sub2; 1.
DR   PANTHER; PTHR48109:SF4; DIHYDROOROTATE DEHYDROGENASE (QUINONE), MITOCHONDRIAL; 1.
DR   PANTHER; PTHR48109; DIHYDROOROTATE DEHYDROGENASE (QUINONE), MITOCHONDRIAL-RELATED; 1.
DR   Pfam; PF01180; DHO_dh; 1.
DR   SUPFAM; SSF51395; FMN-linked oxidoreductases; 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; Pyrimidine biosynthesis; Reference proteome;
KW   Transit peptide; Transmembrane; Transmembrane helix.
FT   CHAIN           1..395
FT                   /note="Dihydroorotate dehydrogenase (quinone),
FT                   mitochondrial"
FT                   /id="PRO_0000233397"
FT   TRANSIT         1..10
FT                   /note="Mitochondrion; not cleaved"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        1..10
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        11..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        31..395
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        214
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   BINDING         95..99
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         99
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         119
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         144..148
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         180
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         211..216
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         211
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         254
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         282
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         283..284
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         305
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         334
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
FT   BINDING         355..356
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   395 AA;  42776 MW;  9D093C1641A44BD0 CRC64;
     MAWRQLKKRA QDAMVILGGG GLLFASYLTA TGDEHFYAEL LMPSLQRLLD PETAHRLAVR
     FTSLGLLPRT TFQDSDMLEV RVLGHKFRNP VGIAAGFDKH GEAVDGLYKM GFGFVEIGSV
     TPEPQEGNPR PRVFRLPEDQ AIINRYGFNS HGLSVVEHRL RARQQTQARL TEDGLPLGIN
     LGKNKTSVDA ASDYAEGVRV LGPLADYLVV NVSSPNTAGL RSLQGKAELR RLLTKVLQER
     DALKVAHKPA VLVKIAPDLT AQDKEDIASV VRELGIDGLI VTNSTVSRPA SLQGALRSEP
     GGLSGKPLRD LSTQTIREMY ALTQGRVPIV GVGGVSSGQD ALEKIRAGAS LVQLYTALTY
     RGPPVVGGVK RELEALLKEQ GFARVTDAIG ADHRR
//