PYRD_HUMAN
ID PYRD_HUMAN Reviewed; 395 AA.
AC Q02127; A8K8C8; Q6P176;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Dihydroorotate dehydrogenase (quinone), mitochondrial;
DE Short=DHOdehase;
DE EC=1.3.5.2 {ECO:0000269|PubMed:8925840};
DE AltName: Full=Dihydroorotate oxidase;
DE Flags: Precursor;
GN Name=DHODH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-7.
RX PubMed=1446837; DOI=10.1016/0378-1119(92)90150-n;
RA Minet M., Dufour M.E., Lacroute F.;
RT "Cloning and sequencing of a human cDNA coding for dihydroorotate
RT dehydrogenase by complementation of the corresponding yeast mutant.";
RL Gene 121:393-396(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=7487077; DOI=10.1006/abbi.1995.0012;
RA Copeland R.A., Davis J.P., Dowling R.L., Lombardo D., Murphy K.B.,
RA Patterson T.A.;
RT "Recombinant human dihydroorotate dehydrogenase: expression, purification,
RT and characterization of a catalytically functional truncated enzyme.";
RL Arch. Biochem. Biophys. 323:79-86(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-7.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8925840; DOI=10.1111/j.1432-1033.1996.0292h.x;
RA Knecht W., Bergjohann U., Gonski S., Kirschbaum B., Loeffler M.;
RT "Functional expression of a fragment of human dihydroorotate dehydrogenase
RT by means of the baculovirus expression vector system, and kinetic
RT investigation of the purified recombinant enzyme.";
RL Eur. J. Biochem. 240:292-301(1996).
RN [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 29-395 IN COMPLEX WITH FMN;
RP DIHYDROOROTATE AND INHIBITORS, AND COFACTOR.
RX PubMed=10673429; DOI=10.1016/s0969-2126(00)00077-0;
RA Liu S., Neidhardt E.A., Grossman T.H., Ocain T., Clardy J.;
RT "Structures of human dihydroorotate dehydrogenase in complex with
RT antiproliferative agents.";
RL Structure 8:25-33(2000).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-395 IN COMPLEX WITH FMN AND
RP INHIBITORS.
RX PubMed=16480261; DOI=10.1021/jm0506975;
RA Baumgartner R., Walloschek M., Kralik M., Gotschlich A., Tasler S.,
RA Mies J., Leban J.;
RT "Dual binding mode of a novel series of DHODH inhibitors.";
RL J. Med. Chem. 49:1239-1247(2006).
RN [12]
RP VARIANTS POADS GLU-19; CYS-135; ARG-152; CYS-199; ALA-202; ASP-202;
RP TRP-244; ILE-284; TRP-346 AND GLY-392.
RX PubMed=19915526; DOI=10.1038/ng.499;
RA Ng S.B., Buckingham K.J., Lee C., Bigham A.W., Tabor H.K., Dent K.M.,
RA Huff C.D., Shannon P.T., Jabs E.W., Nickerson D.A., Shendure J.,
RA Bamshad M.J.;
RT "Exome sequencing identifies the cause of a Mendelian disorder.";
RL Nat. Genet. 42:30-35(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:0000269|PubMed:8925840}.
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:8925840};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:10673429};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:10673429};
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:10673429,
CC ECO:0000269|PubMed:16480261}.
CC -!- INTERACTION:
CC Q02127; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-3928775, EBI-2466594;
CC Q02127; P49638: TTPA; NbExp=3; IntAct=EBI-3928775, EBI-10210710;
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 -!- DISEASE: Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is
CC characterized by severe micrognathia, cleft lip and/or palate,
CC hypoplasia or aplasia of the posterior elements of the limbs, coloboma
CC of the eyelids and supernumerary nipples. POADS is a very rare
CC disorder: only 2 multiplex families, each consisting of 2 affected
CC siblings born to unaffected, nonconsanguineous parents, have been
CC described among a total of around 30 reported cases.
CC {ECO:0000269|PubMed:19915526}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The identification of DHODH defects as the cause of
CC postaxial acrofacial dysostosis (POADS) was obtained via exome
CC sequencing (PubMed:19915526), demonstrating that this method is a
CC powerful tool for identifying genes underlying rare Mendelian
CC disorders. Exome sequencing consists of targeted resequencing of all
CC protein-coding subsequences, which requires around 5% as much
CC sequencing as a whole human genome. {ECO:0000305|PubMed:19915526}.
CC -!- SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; M94065; AAA50163.1; -; mRNA.
DR EMBL; AK292293; BAF84982.1; -; mRNA.
DR EMBL; BC065245; AAH65245.1; -; mRNA.
DR CCDS; CCDS42192.1; -.
DR PIR; PC1219; PC1219.
DR RefSeq; NP_001352.2; NM_001361.4.
DR PDB; 1D3G; X-ray; 1.60 A; A=29-395.
DR PDB; 1D3H; X-ray; 1.80 A; A=29-395.
DR PDB; 2B0M; X-ray; 2.00 A; A=29-395.
DR PDB; 2BXV; X-ray; 2.15 A; A=29-395.
DR PDB; 2FPT; X-ray; 2.40 A; A=29-395.
DR PDB; 2FPV; X-ray; 1.80 A; A=29-395.
DR PDB; 2FPY; X-ray; 2.00 A; A=29-395.
DR PDB; 2FQI; X-ray; 1.95 A; A=29-395.
DR PDB; 2PRH; X-ray; 2.40 A; A=29-395.
DR PDB; 2PRL; X-ray; 2.10 A; A=29-395.
DR PDB; 2PRM; X-ray; 3.00 A; A=29-395.
DR PDB; 2WV8; X-ray; 1.90 A; A=31-395.
DR PDB; 3F1Q; X-ray; 2.00 A; A=29-395.
DR PDB; 3FJ6; X-ray; 1.80 A; A=29-395.
DR PDB; 3FJL; X-ray; 1.90 A; A=29-395.
DR PDB; 3G0U; X-ray; 2.00 A; A=29-395.
DR PDB; 3G0X; X-ray; 1.80 A; A=29-395.
DR PDB; 3KVJ; X-ray; 1.94 A; A=29-395.
DR PDB; 3KVK; X-ray; 2.05 A; A=29-395.
DR PDB; 3KVL; X-ray; 1.85 A; A=29-395.
DR PDB; 3KVM; X-ray; 2.00 A; A=29-395.
DR PDB; 3U2O; X-ray; 2.18 A; A=1-395.
DR PDB; 3W7R; X-ray; 1.68 A; A=29-395.
DR PDB; 3ZWS; X-ray; 1.60 A; A=29-395.
DR PDB; 3ZWT; X-ray; 1.55 A; A=29-395.
DR PDB; 4IGH; X-ray; 1.30 A; A=32-395.
DR PDB; 4JGD; X-ray; 2.05 A; A=29-395.
DR PDB; 4JS3; X-ray; 2.00 A; A=29-395.
DR PDB; 4JTS; X-ray; 2.21 A; A=29-395.
DR PDB; 4JTT; X-ray; 2.10 A; A=29-395.
DR PDB; 4JTU; X-ray; 1.90 A; A=29-395.
DR PDB; 4LS0; X-ray; 2.07 A; A=29-395.
DR PDB; 4LS1; X-ray; 2.20 A; A=29-395.
DR PDB; 4LS2; X-ray; 2.27 A; A=29-395.
DR PDB; 4OQV; X-ray; 1.23 A; A=32-395.
DR PDB; 4RK8; X-ray; 2.22 A; A=29-395.
DR PDB; 4RKA; X-ray; 2.71 A; A=29-395.
DR PDB; 4RLI; X-ray; 2.50 A; A=29-395.
DR PDB; 4RR4; X-ray; 2.38 A; A=29-395.
DR PDB; 4YLW; X-ray; 1.79 A; A=29-395.
DR PDB; 4ZL1; X-ray; 1.86 A; A=29-395.
DR PDB; 4ZMG; X-ray; 1.90 A; A=29-395.
DR PDB; 5H2Z; X-ray; 1.58 A; A=29-395.
DR PDB; 5H73; X-ray; 1.58 A; A=29-395.
DR PDB; 5HIN; X-ray; 1.60 A; A=29-395.
DR PDB; 5HQE; X-ray; 1.62 A; A=29-395.
DR PDB; 5K9C; X-ray; 1.66 A; A=29-395.
DR PDB; 5K9D; X-ray; 1.70 A; A=29-395.
DR PDB; 5MUT; X-ray; 1.75 A; A=31-395.
DR PDB; 5MVC; X-ray; 1.85 A; A=29-395.
DR PDB; 5MVD; X-ray; 1.95 A; A=33-395.
DR PDB; 5TCE; NMR; -; A=32-65.
DR PDB; 5ZF4; X-ray; 1.66 A; A=29-395.
DR PDB; 5ZF7; X-ray; 1.79 A; A=29-395.
DR PDB; 5ZF8; X-ray; 1.70 A; A=29-395.
DR PDB; 5ZF9; X-ray; 1.77 A; A=29-395.
DR PDB; 5ZFA; X-ray; 1.75 A; A=29-395.
DR PDB; 5ZFB; X-ray; 2.00 A; A=29-395.
DR PDB; 6CJF; X-ray; 1.63 A; A/B=32-395.
DR PDB; 6CJG; X-ray; 2.85 A; A=32-395.
DR PDB; 6ET4; X-ray; 1.70 A; A=29-395.
DR PDB; 6FMD; X-ray; 1.58 A; A=1-395.
DR PDB; 6GK0; X-ray; 1.85 A; A=29-395.
DR PDB; 6IDJ; X-ray; 1.90 A; A=29-395.
DR PDB; 6J3B; X-ray; 1.60 A; A=30-395.
DR PDB; 6J3C; X-ray; 1.85 A; A=30-395.
DR PDB; 6JMD; X-ray; 1.78 A; A=30-395.
DR PDB; 6JME; X-ray; 1.80 A; A=30-395.
DR PDB; 6LP6; X-ray; 1.79 A; A=30-395.
DR PDB; 6LP7; X-ray; 1.80 A; A=30-395.
DR PDB; 6LP8; X-ray; 1.79 A; A=30-395.
DR PDB; 6LZL; X-ray; 1.98 A; A=31-395.
DR PDB; 6M2B; X-ray; 1.76 A; A=29-395.
DR PDB; 6OC0; X-ray; 1.40 A; A=29-395.
DR PDB; 6OC1; X-ray; 2.70 A; A=29-395.
DR PDB; 6QU7; X-ray; 1.52 A; A=30-395.
DR PDB; 6SYP; X-ray; 1.80 A; AAA=1-395.
DR PDB; 6VND; X-ray; 1.97 A; A=29-395.
DR PDB; 7K2U; X-ray; 1.73 A; A=29-395.
DR PDBsum; 1D3G; -.
DR PDBsum; 1D3H; -.
DR PDBsum; 2B0M; -.
DR PDBsum; 2BXV; -.
DR PDBsum; 2FPT; -.
DR PDBsum; 2FPV; -.
DR PDBsum; 2FPY; -.
DR PDBsum; 2FQI; -.
DR PDBsum; 2PRH; -.
DR PDBsum; 2PRL; -.
DR PDBsum; 2PRM; -.
DR PDBsum; 2WV8; -.
DR PDBsum; 3F1Q; -.
DR PDBsum; 3FJ6; -.
DR PDBsum; 3FJL; -.
DR PDBsum; 3G0U; -.
DR PDBsum; 3G0X; -.
DR PDBsum; 3KVJ; -.
DR PDBsum; 3KVK; -.
DR PDBsum; 3KVL; -.
DR PDBsum; 3KVM; -.
DR PDBsum; 3U2O; -.
DR PDBsum; 3W7R; -.
DR PDBsum; 3ZWS; -.
DR PDBsum; 3ZWT; -.
DR PDBsum; 4IGH; -.
DR PDBsum; 4JGD; -.
DR PDBsum; 4JS3; -.
DR PDBsum; 4JTS; -.
DR PDBsum; 4JTT; -.
DR PDBsum; 4JTU; -.
DR PDBsum; 4LS0; -.
DR PDBsum; 4LS1; -.
DR PDBsum; 4LS2; -.
DR PDBsum; 4OQV; -.
DR PDBsum; 4RK8; -.
DR PDBsum; 4RKA; -.
DR PDBsum; 4RLI; -.
DR PDBsum; 4RR4; -.
DR PDBsum; 4YLW; -.
DR PDBsum; 4ZL1; -.
DR PDBsum; 4ZMG; -.
DR PDBsum; 5H2Z; -.
DR PDBsum; 5H73; -.
DR PDBsum; 5HIN; -.
DR PDBsum; 5HQE; -.
DR PDBsum; 5K9C; -.
DR PDBsum; 5K9D; -.
DR PDBsum; 5MUT; -.
DR PDBsum; 5MVC; -.
DR PDBsum; 5MVD; -.
DR PDBsum; 5TCE; -.
DR PDBsum; 5ZF4; -.
DR PDBsum; 5ZF7; -.
DR PDBsum; 5ZF8; -.
DR PDBsum; 5ZF9; -.
DR PDBsum; 5ZFA; -.
DR PDBsum; 5ZFB; -.
DR PDBsum; 6CJF; -.
DR PDBsum; 6CJG; -.
DR PDBsum; 6ET4; -.
DR PDBsum; 6FMD; -.
DR PDBsum; 6GK0; -.
DR PDBsum; 6IDJ; -.
DR PDBsum; 6J3B; -.
DR PDBsum; 6J3C; -.
DR PDBsum; 6JMD; -.
DR PDBsum; 6JME; -.
DR PDBsum; 6LP6; -.
DR PDBsum; 6LP7; -.
DR PDBsum; 6LP8; -.
DR PDBsum; 6LZL; -.
DR PDBsum; 6M2B; -.
DR PDBsum; 6OC0; -.
DR PDBsum; 6OC1; -.
DR PDBsum; 6QU7; -.
DR PDBsum; 6SYP; -.
DR PDBsum; 6VND; -.
DR PDBsum; 7K2U; -.
DR AlphaFoldDB; Q02127; -.
DR SMR; Q02127; -.
DR BioGRID; 108068; 39.
DR IntAct; Q02127; 6.
DR STRING; 9606.ENSP00000219240; -.
DR BindingDB; Q02127; -.
DR ChEMBL; CHEMBL1966; -.
DR DrugBank; DB07559; (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide.
DR DrugBank; DB07561; (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide.
DR DrugBank; DB08172; (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide.
DR DrugBank; DB08169; (2Z)-N-biphenyl-4-yl-2-cyano-3-cyclopropyl-3-hydroxyprop-2-enamide.
DR DrugBank; DB07443; (2Z)-N-biphenyl-4-yl-2-cyano-3-hydroxybut-2-enamide.
DR DrugBank; DB07978; 2-({[2,3,5,6-TETRAFLUORO-3'-(TRIFLUOROMETHOXY)BIPHENYL-4-YL]AMINO}CARBONYL)CYCLOPENTA-1,3-DIENE-1-CARBOXYLIC ACID.
DR DrugBank; DB07975; 2-({[3,5-DIFLUORO-3'-(TRIFLUOROMETHOXY)BIPHENYL-4-YL]AMINO}CARBONYL)CYCLOPENT-1-ENE-1-CARBOXYLIC ACID.
DR DrugBank; DB04281; 2-[4-(4-Chlorophenyl)Cyclohexylidene]-3,4-Dihydroxy-1(2h)-Naphthalenone.
DR DrugBank; DB08249; 3,6,9,12,15-PENTAOXATRICOSAN-1-OL.
DR DrugBank; DB07977; 3-({[3,5-DIFLUORO-3'-(TRIFLUOROMETHOXY)BIPHENYL-4-YL]AMINO}CARBONYL)THIOPHENE-2-CARBOXYLIC ACID.
DR DrugBank; DB07976; 3-{[(3-FLUORO-3'-METHOXYBIPHENYL-4-YL)AMINO]CARBONYL}THIOPHENE-2-CARBOXYLIC ACID.
DR DrugBank; DB04583; 5-Carbamoyl-1,1':4',1''-terphenyl-3-carboxylic acid.
DR DrugBank; DB08008; 5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine.
DR DrugBank; DB01117; Atovaquone.
DR DrugBank; DB03523; Brequinar.
DR DrugBank; DB03480; Brequinar Analog.
DR DrugBank; DB02613; Capric dimethyl amine oxide.
DR DrugBank; DB04147; Dodecyldimethylamine N-oxide.
DR DrugBank; DB03247; Flavin mononucleotide.
DR DrugBank; DB01097; Leflunomide.
DR DrugBank; DB06481; Manitimus.
DR DrugBank; DB08006; N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine.
DR DrugBank; DB02262; Orotic acid.
DR DrugBank; DB05125; SC12267.
DR DrugBank; DB08880; Teriflunomide.
DR DrugBank; DB07646; UNDECYLAMINE-N,N-DIMETHYL-N-OXIDE.
DR DrugCentral; Q02127; -.
DR GuidetoPHARMACOLOGY; 2604; -.
DR iPTMnet; Q02127; -.
DR PhosphoSitePlus; Q02127; -.
DR BioMuta; DHODH; -.
DR DMDM; 56405372; -.
DR EPD; Q02127; -.
DR jPOST; Q02127; -.
DR MassIVE; Q02127; -.
DR MaxQB; Q02127; -.
DR PaxDb; Q02127; -.
DR PeptideAtlas; Q02127; -.
DR PRIDE; Q02127; -.
DR ProteomicsDB; 58051; -.
DR TopDownProteomics; Q02127; -.
DR Antibodypedia; 2311; 344 antibodies from 35 providers.
DR DNASU; 1723; -.
DR Ensembl; ENST00000219240.9; ENSP00000219240.4; ENSG00000102967.12.
DR GeneID; 1723; -.
DR KEGG; hsa:1723; -.
DR MANE-Select; ENST00000219240.9; ENSP00000219240.4; NM_001361.5; NP_001352.2.
DR UCSC; uc002fbp.4; human.
DR CTD; 1723; -.
DR DisGeNET; 1723; -.
DR GeneCards; DHODH; -.
DR HGNC; HGNC:2867; DHODH.
DR HPA; ENSG00000102967; Tissue enriched (liver).
DR MalaCards; DHODH; -.
DR MIM; 126064; gene.
DR MIM; 263750; phenotype.
DR neXtProt; NX_Q02127; -.
DR OpenTargets; ENSG00000102967; -.
DR Orphanet; 246; Postaxial acrofacial dysostosis.
DR PharmGKB; PA27327; -.
DR VEuPathDB; HostDB:ENSG00000102967; -.
DR eggNOG; KOG1436; Eukaryota.
DR GeneTree; ENSGT00500000044924; -.
DR InParanoid; Q02127; -.
DR OMA; ERIKMGA; -.
DR OrthoDB; 1194348at2759; -.
DR PhylomeDB; Q02127; -.
DR TreeFam; TF105973; -.
DR BRENDA; 1.3.5.2; 2681.
DR PathwayCommons; Q02127; -.
DR Reactome; R-HSA-500753; Pyrimidine biosynthesis.
DR SABIO-RK; Q02127; -.
DR SignaLink; Q02127; -.
DR SIGNOR; Q02127; -.
DR UniPathway; UPA00070; UER00946.
DR BioGRID-ORCS; 1723; 269 hits in 1090 CRISPR screens.
DR ChiTaRS; DHODH; human.
DR EvolutionaryTrace; Q02127; -.
DR GenomeRNAi; 1723; -.
DR Pharos; Q02127; Tclin.
DR PRO; PR:Q02127; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q02127; protein.
DR Bgee; ENSG00000102967; Expressed in right lobe of liver and 107 other tissues.
DR ExpressionAtlas; Q02127; baseline and differential.
DR Genevisible; Q02127; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004151; F:dihydroorotase activity; IEA:Ensembl.
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 GO; GO:0006225; P:UDP biosynthetic process; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Disease variant; 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_0000029884"
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 BINDING 95..99
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 99
FT /ligand="substrate"
FT BINDING 119
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 144..148
FT /ligand="substrate"
FT BINDING 180
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 211..216
FT /ligand="substrate"
FT BINDING 211
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 254
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 282
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 283..284
FT /ligand="substrate"
FT BINDING 305
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 334
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT BINDING 355..356
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:10673429,
FT ECO:0000269|PubMed:16480261"
FT VARIANT 7
FT /note="K -> Q (in dbSNP:rs3213422)"
FT /evidence="ECO:0000269|PubMed:1446837,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_022094"
FT VARIANT 19
FT /note="G -> E (in POADS; dbSNP:rs267606765)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062412"
FT VARIANT 135
FT /note="R -> C (in POADS; dbSNP:rs201230446)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062413"
FT VARIANT 152
FT /note="G -> R (in POADS; dbSNP:rs267606766)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062414"
FT VARIANT 199
FT /note="R -> C (in POADS; dbSNP:rs267606769)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062415"
FT VARIANT 202
FT /note="G -> A (in POADS; dbSNP:rs267606767)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062416"
FT VARIANT 202
FT /note="G -> D (in POADS; dbSNP:rs267606767)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062417"
FT VARIANT 244
FT /note="R -> W (in POADS; dbSNP:rs267606768)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062418"
FT VARIANT 284
FT /note="T -> I (in POADS)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062419"
FT VARIANT 346
FT /note="R -> W (in POADS; dbSNP:rs201947120)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062420"
FT VARIANT 392
FT /note="D -> G (in POADS; dbSNP:rs779076692)"
FT /evidence="ECO:0000269|PubMed:19915526"
FT /id="VAR_062421"
FT CONFLICT 1..2
FT /note="MA -> KLP (in Ref. 1; AAA50163)"
FT /evidence="ECO:0000305"
FT HELIX 34..39
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 41..48
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 51..63
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:4OQV"
FT TURN 95..100
FT /evidence="ECO:0007829|PDB:6OC0"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6OC0"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 113..120
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 153..161
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 164..172
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 190..201
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:6OC1"
FT TURN 218..221
FT /evidence="ECO:0007829|PDB:6QU7"
FT HELIX 226..241
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 261..274
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:5K9C"
FT TURN 295..298
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 299..305
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:4OQV"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 338..347
FT /evidence="ECO:0007829|PDB:4OQV"
FT STRAND 349..355
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 356..361
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 364..379
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:4OQV"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:4OQV"
SQ SEQUENCE 395 AA; 42867 MW; 072C3169E78C6440 CRC64;
MAWRHLKKRA QDAVIILGGG GLLFASYLMA TGDERFYAEH LMPTLQGLLD PESAHRLAVR
FTSLGLLPRA RFQDSDMLEV RVLGHKFRNP VGIAAGFDKH GEAVDGLYKM GFGFVEIGSV
TPKPQEGNPR PRVFRLPEDQ AVINRYGFNS HGLSVVEHRL RARQQKQAKL TEDGLPLGVN
LGKNKTSVDA AEDYAEGVRV LGPLADYLVV NVSSPNTAGL RSLQGKAELR RLLTKVLQER
DGLRRVHRPA VLVKIAPDLT SQDKEDIASV VKELGIDGLI VTNTTVSRPA GLQGALRSET
GGLSGKPLRD LSTQTIREMY ALTQGRVPII GVGGVSSGQD ALEKIRAGAS LVQLYTALTF
WGPPVVGKVK RELEALLKEQ GFGGVTDAIG ADHRR
