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Database: UniProt
Entry: O89000
LinkDB: O89000
Original site: O89000 
ID   DPYD_RAT                Reviewed;        1025 AA.
AC   O89000;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   10-APR-2019, entry version 132.
DE   RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)];
DE            Short=DHPDHase;
DE            Short=DPD;
DE            EC=1.3.1.2;
DE   AltName: Full=Dihydrothymine dehydrogenase;
DE   AltName: Full=Dihydrouracil dehydrogenase;
GN   Name=Dpyd; Synonyms=DPD;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar; TISSUE=Liver;
RX   PubMed=9819714;
RA   Kimura M., Fujimoto Sakata S., Matoba Y., Matsuda K., Kontani Y.,
RA   Kaneko M., Tamaki N.;
RT   "Cloning of rat dihydropyrimidine dehydrogenase and correlation of its
RT   mRNA increase in the rat liver with age.";
RL   J. Nutr. Sci. Vitaminol. 44:537-546(1998).
CC   -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC       reduction of uracil and thymine (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,6-dihydrouracil + NADP(+) = H(+) + NADPH + uracil;
CC         Xref=Rhea:RHEA:18093, ChEBI:CHEBI:15378, ChEBI:CHEBI:15901,
CC         ChEBI:CHEBI:17568, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         EC=1.3.1.2;
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250};
CC       Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron
CC       atoms per subunit. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC   -!- ACTIVITY REGULATION: Inactivated by 5-iodouracil. {ECO:0000250}.
CC   -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC       {ECO:0000305}.
DR   EMBL; D85035; BAA33218.1; -; mRNA.
DR   RefSeq; NP_112289.1; NM_031027.1.
DR   UniGene; Rn.158382; -.
DR   ProteinModelPortal; O89000; -.
DR   SMR; O89000; -.
DR   STRING; 10116.ENSRNOP00000052583; -.
DR   iPTMnet; O89000; -.
DR   PhosphoSitePlus; O89000; -.
DR   PaxDb; O89000; -.
DR   PRIDE; O89000; -.
DR   GeneID; 81656; -.
DR   KEGG; rno:81656; -.
DR   UCSC; RGD:621218; rat.
DR   CTD; 1806; -.
DR   RGD; 621218; Dpyd.
DR   eggNOG; ENOG410ISNJ; Eukaryota.
DR   eggNOG; COG0493; LUCA.
DR   HOVERGEN; HBG004351; -.
DR   InParanoid; O89000; -.
DR   KO; K00207; -.
DR   OrthoDB; 592753at2759; -.
DR   PhylomeDB; O89000; -.
DR   BioCyc; MetaCyc:MONOMER-15405; -.
DR   SABIO-RK; O89000; -.
DR   UniPathway; UPA00131; -.
DR   PRO; PR:O89000; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR   GO; GO:0004159; F:dihydrouracil dehydrogenase (NAD+) activity; IDA:RGD.
DR   GO; GO:0071949; F:FAD binding; IDA:RGD.
DR   GO; GO:0005506; F:iron ion binding; IDA:RGD.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IBA:GO_Central.
DR   GO; GO:0003954; F:NADH dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0002058; F:uracil binding; IDA:RGD.
DR   GO; GO:0007568; P:aging; IEP:RGD.
DR   GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0007623; P:circadian rhythm; IDA:RGD.
DR   GO; GO:0006208; P:pyrimidine nucleobase catabolic process; IDA:RGD.
DR   GO; GO:0042493; P:response to drug; IDA:RGD.
DR   GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR   GO; GO:0007584; P:response to nutrient; IDA:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR   GO; GO:0006214; P:thymidine catabolic process; ISS:UniProtKB.
DR   GO; GO:0006210; P:thymine catabolic process; IBA:GO_Central.
DR   GO; GO:0006212; P:uracil catabolic process; ISS:UniProtKB.
DR   GO; GO:0019860; P:uracil metabolic process; IDA:RGD.
DR   Gene3D; 1.10.1060.10; -; 1.
DR   Gene3D; 3.20.20.70; -; 1.
DR   Gene3D; 3.50.50.60; -; 2.
DR   InterPro; IPR017896; 4Fe4S_Fe-S-bd.
DR   InterPro; IPR017900; 4Fe4S_Fe_S_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR005720; Dihydroorotate_DH.
DR   InterPro; IPR028261; DPD_II.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR023753; FAD/NAD-binding_dom.
DR   InterPro; IPR009051; Helical_ferredxn.
DR   Pfam; PF01180; DHO_dh; 1.
DR   Pfam; PF14691; Fer4_20; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   SUPFAM; SSF46548; SSF46548; 1.
DR   TIGRFAMs; TIGR01037; pyrD_sub1_fam; 1.
DR   PROSITE; PS00198; 4FE4S_FER_1; 1.
DR   PROSITE; PS51379; 4FE4S_FER_2; 3.
PE   2: Evidence at transcript level;
KW   4Fe-4S; Acetylation; Complete proteome; Cytoplasm; FAD; Flavoprotein;
KW   FMN; Iron; Iron-sulfur; Metal-binding; NADP; Nucleotide-binding;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN         1   1025       Dihydropyrimidine dehydrogenase
FT                                [NADP(+)].
FT                                /FTId=PRO_0000327502.
FT   DOMAIN       69    100       4Fe-4S ferredoxin-type 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      944    976       4Fe-4S ferredoxin-type 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      978   1007       4Fe-4S ferredoxin-type 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   NP_BIND     194    198       FAD. {ECO:0000250}.
FT   NP_BIND     218    226       FAD. {ECO:0000250}.
FT   NP_BIND     340    343       NADP. {ECO:0000250}.
FT   NP_BIND     364    365       NADP. {ECO:0000250}.
FT   NP_BIND     437    439       NADP. {ECO:0000250}.
FT   NP_BIND     480    489       FAD. {ECO:0000250}.
FT   NP_BIND     481    487       NADP. {ECO:0000250}.
FT   NP_BIND     574    575       FMN. {ECO:0000250}.
FT   NP_BIND     793    795       FMN. {ECO:0000250}.
FT   NP_BIND     816    817       FMN. {ECO:0000250}.
FT   REGION      668    670       Substrate binding. {ECO:0000250}.
FT   REGION      736    737       Substrate binding. {ECO:0000250}.
FT   ACT_SITE    671    671       Proton acceptor. {ECO:0000250}.
FT   METAL        79     79       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        82     82       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        87     87       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        91     91       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       130    130       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       136    136       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       140    140       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL       156    156       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       953    953       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       956    956       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       959    959       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       963    963       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       986    986       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       989    989       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       992    992       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       996    996       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   BINDING     129    129       FAD; via carbonyl oxygen. {ECO:0000250}.
FT   BINDING     235    235       FAD. {ECO:0000250}.
FT   BINDING     371    371       NADP. {ECO:0000250}.
FT   BINDING     550    550       FMN. {ECO:0000250}.
FT   BINDING     609    609       Substrate. {ECO:0000250}.
FT   BINDING     709    709       FMN. {ECO:0000250}.
FT   BINDING     767    767       FMN; via amide nitrogen. {ECO:0000250}.
FT   MOD_RES     384    384       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q12882}.
FT   MOD_RES     905    905       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q12882}.
SQ   SEQUENCE   1025 AA;  111468 MW;  07859E73D249828C CRC64;
     MAGVLSRDAP DIESILALNP RIQAHATLRS TMAKKLDKKH WKRNTDKNCF ICEKLENNFD
     DIKHTTLGER GALREAVRCL KCADAPCQKS CPTSLDIKSF ITSIANKNYY GAAKLIFSDN
     PLGLTCGMVC PTSDLCVGGC NLHATEEGPI NIGGLQQFAT EVFKAMNIPQ IRSPLLPPPE
     HMPEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
     VNFEIELMKD LGVKIICGKS ISTDEMTLST LKENGYKAAF IGIGLPEPKK DHIFQGLTQV
     QGFYTSKDFL PLVAKGSKPG MCACHSPLPS VRGAVIVLGA GDTAFDCATS ALRCGARRVF
     IVFRKGFANI RAVPEEMELA KEEKCEFLPF LSPRKVIVKD GKIVGMQFVR TEQDETGNWV
     EDEEQIVRLK ADVVISPFGS VLDDPKVIEA LSPIKFNRWG LPEVNPETMQ TSEPWVFAGG
     DVVGMANTTV ESVNDGKQAS WYIHEYIQAQ YGALVPSQPT LPLFYTPVDL VDISVEMAGL
     RFPNPFGLAS ATPATSTPMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPLY
     GPGQSSFLNI ELISEKTAAY WCHSVTELKA DFPDNILIAS IMCSYNKNDW MELSKMAEAS
     GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ SVRVPFFAKL TPNVTDIVSI
     ARAAKEGGAD GVTATNTVSG LMGLKADGSP WPSVGSGKRT TYGGVSGTTI RPIALRAVTA
     IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
     KSIEELSDWD GQSPPTMSHQ KGKPVPHIAE LMGQKLPSFG PYLERRKKIL AASKIRENDQ
     NRACSPLQRK HFNSQKPIPA IKDVIGKSLQ YLGTFGELNI MEQVVALIDE EMCINCGKCY
     MTCNDSGYQA IQFDPETHLP TVSDTCTGCT LCLSVCPIMD CIRMVSRATP YEPKRGLPLA
     VKPVC
//
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