PYRD_BOVIN
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 03-AUG-2022, entry version 96.
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; Q5E9W3; -.
DR PRIDE; Q5E9W3; -.
DR GeneID; 533873; -.
DR KEGG; bta:533873; -.
DR CTD; 1723; -.
DR eggNOG; KOG1436; Eukaryota.
DR InParanoid; Q5E9W3; -.
DR OrthoDB; 1194348at2759; -.
DR SABIO-RK; Q5E9W3; -.
DR UniPathway; UPA00070; UER00946.
DR Proteomes; UP000009136; Unplaced.
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: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; -; 1.
DR HAMAP; MF_00225; DHO_dh_type2; 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; 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
