PYRD_RAT
ID PYRD_RAT Reviewed; 395 AA.
AC Q63707;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE Short=DHOdehase;
DE EC=1.3.5.2 {ECO:0000250|UniProtKB:Q02127};
DE AltName: Full=Dihydroorotate oxidase;
DE Flags: Precursor;
GN Name=Dhodh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=7660999; DOI=10.1007/978-1-4615-2584-4_144;
RA Rotgeri A., Loeffler M.;
RT "Molecular cloning and sequence analyses of rat liver dihydroorotate
RT dehydrogenase.";
RL Adv. Exp. Med. Biol. 370:693-697(1994).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=10727948; DOI=10.1046/j.1432-1327.2000.01213.x;
RA Rawls J., Knecht W., Diekert K., Lill R., Loeffler M.;
RT "Requirements for the mitochondrial import and localization of
RT dihydroorotate dehydrogenase.";
RL Eur. J. Biochem. 267:2079-2087(2000).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 30-395 IN COMPLEX WITH FMN;
RP OROTATE AND INHIBITOR, AND COFACTOR.
RX PubMed=15044733; DOI=10.1110/ps.03533004;
RA Hansen M., Le Nours J., Johansson E., Antal T., Ullrich A., Loeffler M.,
RA Larsen S.;
RT "Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes
RT variations in the membrane-associated N-terminal domain.";
RL Protein Sci. 13:1031-1042(2004).
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:0000250|UniProtKB:Q02127}.
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:0000250|UniProtKB:Q02127};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:15044733};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:15044733};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC orotate from (S)-dihydroorotate (quinone route): step 1/1.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15044733}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:10727948}; Single-pass membrane protein
CC {ECO:0000269|PubMed:10727948}.
CC -!- PTM: The uncleaved transit peptide is required for mitochondrial
CC targeting and proper membrane integration.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; X80778; CAA56765.1; -; mRNA.
DR PIR; A59277; S47435.
DR RefSeq; NP_001008553.1; NM_001008553.1.
DR RefSeq; XP_006255663.1; XM_006255601.3.
DR RefSeq; XP_008770751.1; XM_008772529.2.
DR PDB; 1UUM; X-ray; 2.30 A; A/B=30-395.
DR PDB; 1UUO; X-ray; 2.44 A; A=30-395.
DR PDB; 4ORI; X-ray; 1.50 A; A=32-395.
DR PDBsum; 1UUM; -.
DR PDBsum; 1UUO; -.
DR PDBsum; 4ORI; -.
DR AlphaFoldDB; Q63707; -.
DR SMR; Q63707; -.
DR STRING; 10116.ENSRNOP00000061315; -.
DR BindingDB; Q63707; -.
DR ChEMBL; CHEMBL2383; -.
DR DrugCentral; Q63707; -.
DR GuidetoPHARMACOLOGY; 2604; -.
DR iPTMnet; Q63707; -.
DR PhosphoSitePlus; Q63707; -.
DR jPOST; Q63707; -.
DR PaxDb; Q63707; -.
DR PRIDE; Q63707; -.
DR GeneID; 65156; -.
DR KEGG; rno:65156; -.
DR UCSC; RGD:68352; rat.
DR CTD; 1723; -.
DR RGD; 68352; Dhodh.
DR VEuPathDB; HostDB:ENSRNOG00000015063; -.
DR eggNOG; KOG1436; Eukaryota.
DR HOGENOM; CLU_013640_0_2_1; -.
DR InParanoid; Q63707; -.
DR OMA; ERIKMGA; -.
DR OrthoDB; 1194348at2759; -.
DR PhylomeDB; Q63707; -.
DR TreeFam; TF105973; -.
DR BRENDA; 1.3.5.2; 5301.
DR Reactome; R-RNO-500753; Pyrimidine biosynthesis.
DR SABIO-RK; Q63707; -.
DR UniPathway; UPA00070; UER00946.
DR EvolutionaryTrace; Q63707; -.
DR PRO; PR:Q63707; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000015063; Expressed in ovary and 20 other tissues.
DR Genevisible; Q63707; RN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0004151; F:dihydroorotase activity; ISO:RGD.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IDA:RGD.
DR GO; GO:0010181; F:FMN binding; IDA:RGD.
DR GO; GO:0048038; F:quinone binding; IPI:RGD.
DR GO; GO:0048039; F:ubiquinone binding; IDA:RGD.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IDA:RGD.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthetic process; IBA:GO_Central.
DR GO; GO:0090140; P:regulation of mitochondrial fission; IMP:RGD.
DR GO; GO:0031000; P:response to caffeine; IEP:RGD.
DR GO; GO:1903576; P:response to L-arginine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006225; P:UDP biosynthetic process; ISO:RGD.
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 3D-structure; Flavoprotein; FMN; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Oxidoreductase; Pyrimidine biosynthesis;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT CHAIN 1..395
FT /note="Dihydroorotate dehydrogenase (quinone),
FT mitochondrial"
FT /id="PRO_0000029886"
FT TRANSIT 1..10
FT /note="Mitochondrion; not cleaved"
FT TOPO_DOM 1..10
FT /note="Mitochondrial intermembrane"
FT TRANSMEM 11..30
FT /note="Helical"
FT TOPO_DOM 31..395
FT /note="Mitochondrial matrix"
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:0000269|PubMed:15044733"
FT BINDING 99
FT /ligand="substrate"
FT BINDING 119
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT BINDING 144..148
FT /ligand="substrate"
FT BINDING 180
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
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:0000269|PubMed:15044733"
FT BINDING 211
FT /ligand="substrate"
FT BINDING 254
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT BINDING 282
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT BINDING 283..284
FT /ligand="substrate"
FT BINDING 305
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT BINDING 334
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT BINDING 355..356
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:15044733"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 41..48
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 51..63
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1UUM"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 113..120
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:4ORI"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 153..162
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 164..172
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 190..201
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 206..211
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 226..241
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:1UUM"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 261..274
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 299..305
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:4ORI"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 338..346
FT /evidence="ECO:0007829|PDB:4ORI"
FT STRAND 350..355
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 356..361
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 364..379
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:4ORI"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:4ORI"
SQ SEQUENCE 395 AA; 42663 MW; 4C7E1A9C5E5E60EB CRC64;
MAWRQLRKRA LDAVIILGGG GLLFTSYLTA TGDDHFYAEY LMPGLQRLLD PESAHRLAVR
VTSLGLLPRA TFQDSDMLEV KVLGHKFRNP VGIAAGFDKN GEAVDGLYKL GFGFVEVGSV
TPQPQEGNPR PRVFRLPEDQ AVINRYGFNS HGLSVVEHRL RARQQKQAQL TADGLPLGIN
LGKNKTSEDA AADYAEGVRT LGPLADYLVV NVSSPNTAGL RSLQGKTELR HLLSKVLQER
DALKGTRKPA VLVKIAPDLT AQDKEDIASV ARELGIDGLI VTNTTVSRPV GLQGALRSET
GGLSGKPLRD LSTQTIREMY ALTQGRIPII GVGGVSSGQD ALEKIQAGAS LVQLYTALIF
LGPPVVVRVK RELEALLKER GFTTVTDAIG ADHRR
