PYRD_MOUSE
ID PYRD_MOUSE Reviewed; 395 AA.
AC O35435;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 2.
DT 03-AUG-2022, entry version 163.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Knecht W., Ullrich A., Loeffler M.;
RT "Cloning of murine dihydroorotate dehydrogenase.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000250|UniProtKB:Q02127};
CC Note=Binds 1 FMN per subunit. {ECO:0000250|UniProtKB:Q02127};
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; AF029667; AAB82948.2; -; mRNA.
DR EMBL; BC019542; AAH19542.1; -; mRNA.
DR EMBL; BC027829; AAH27829.1; -; mRNA.
DR EMBL; BC045206; AAH45206.1; -; mRNA.
DR CCDS; CCDS40471.1; -.
DR RefSeq; NP_064430.1; NM_020046.3.
DR AlphaFoldDB; O35435; -.
DR SMR; O35435; -.
DR BioGRID; 208162; 40.
DR IntAct; O35435; 1.
DR STRING; 10090.ENSMUSP00000070303; -.
DR BindingDB; O35435; -.
DR ChEMBL; CHEMBL2991; -.
DR DrugCentral; O35435; -.
DR GuidetoPHARMACOLOGY; 2604; -.
DR PhosphoSitePlus; O35435; -.
DR EPD; O35435; -.
DR MaxQB; O35435; -.
DR PaxDb; O35435; -.
DR PeptideAtlas; O35435; -.
DR PRIDE; O35435; -.
DR ProteomicsDB; 300213; -.
DR Antibodypedia; 2311; 344 antibodies from 35 providers.
DR DNASU; 56749; -.
DR Ensembl; ENSMUST00000123605; ENSMUSP00000115934; ENSMUSG00000031730.
DR GeneID; 56749; -.
DR KEGG; mmu:56749; -.
DR UCSC; uc009nip.1; mouse.
DR CTD; 1723; -.
DR MGI; MGI:1928378; Dhodh.
DR VEuPathDB; HostDB:ENSMUSG00000031730; -.
DR eggNOG; KOG1436; Eukaryota.
DR GeneTree; ENSGT00500000044924; -.
DR HOGENOM; CLU_013640_0_2_1; -.
DR InParanoid; O35435; -.
DR OMA; ERIKMGA; -.
DR OrthoDB; 1194348at2759; -.
DR PhylomeDB; O35435; -.
DR TreeFam; TF105973; -.
DR Reactome; R-MMU-500753; Pyrimidine biosynthesis.
DR UniPathway; UPA00070; UER00946.
DR BioGRID-ORCS; 56749; 25 hits in 76 CRISPR screens.
DR ChiTaRS; Dhodh; mouse.
DR PRO; PR:O35435; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O35435; protein.
DR Bgee; ENSMUSG00000031730; Expressed in yolk sac and 268 other tissues.
DR ExpressionAtlas; O35435; baseline and differential.
DR Genevisible; O35435; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0004151; F:dihydroorotase activity; IMP:MGI.
DR GO; GO:0004152; F:dihydroorotate dehydrogenase activity; IMP:MGI.
DR GO; GO:0010181; F:FMN binding; ISO:MGI.
DR GO; GO:0048038; F:quinone binding; ISO:MGI.
DR GO; GO:0048039; F:ubiquinone binding; ISO:MGI.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; ISO:MGI.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthetic process; IBA:GO_Central.
DR GO; GO:0090140; P:regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:0006225; P:UDP biosynthetic process; IMP:MGI.
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_0000029885"
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:0000255"
FT TRANSMEM 11..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..395
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
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; 42700 MW; 84F2D93D0646E39D CRC64;
MAWRQLRKRA LDAAIILGGG GLLFTSYLTA TGDDHFYAEY LMPALQRLLD PESAHRLAVR
VISLGLLPRA TFQDSNMLEV RVLGHKFRNP VGIAAGFDKH GEAVDGLYKL GFGFVEVGSV
TPQPQEGNPR PRVFRLPEDQ AVINRYGFNS HGLSAVEHRL RARQQKQTQL TTDGLPLGIN
LGKNKTSVDA AADYVEGVRI LGPLADYLVV NVSSPNTAGL RSLQGKTELR RLLSKVLQER
DALKGPQKPA VLVKIAPDLT AQDKEDIASV ARELGIDGLI ITNTTVSRPV GLQGALRSET
GGLSGKPLRD LSTQTIREMY ALTQGTIPII GVGGVSSGQD ALEKIQAGAS LVQLYTALTF
LGPPVVARVK RELEALLKER GFNTVTDAIG VDHRR
