DPYD_RAT
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 03-AUG-2022, entry version 144.
DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)];
DE Short=DHPDHase;
DE Short=DPD;
DE EC=1.3.1.2 {ECO:0000250|UniProtKB:Q12882};
DE AltName: Full=Dihydrothymine dehydrogenase;
DE AltName: Full=Dihydrouracil dehydrogenase;
GN Name=Dpyd {ECO:0000312|RGD:621218}; Synonyms=DPD;
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=Wistar; TISSUE=Liver;
RX PubMed=9819714; DOI=10.3177/jnsv.44.537;
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 mRNA
RT 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. Also involved the degradation of the
CC chemotherapeutic drug 5-fluorouracil. {ECO:0000250|UniProtKB:Q12882}.
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; EC=1.3.1.2;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18095;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,6-dihydrothymine + NADP(+) = H(+) + NADPH + thymine;
CC Xref=Rhea:RHEA:58284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17821,
CC ChEBI:CHEBI:27468, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.2;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58286;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 2 FAD. {ECO:0000250|UniProtKB:Q28943};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 2 FMN. {ECO:0000250|UniProtKB:Q28943};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms
CC per subunit. {ECO:0000250|UniProtKB:Q28943};
CC -!- ACTIVITY REGULATION: Inactivated by 5-iodouracil.
CC {ECO:0000250|UniProtKB:Q28943}.
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000250|UniProtKB:Q12882}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12882}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q12882}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; D85035; BAA33218.1; -; mRNA.
DR RefSeq; NP_112289.1; NM_031027.1.
DR AlphaFoldDB; 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; KOG1799; Eukaryota.
DR InParanoid; O89000; -.
DR OrthoDB; 592753at2759; -.
DR PhylomeDB; O89000; -.
DR BioCyc; MetaCyc:MON-15405; -.
DR Reactome; R-RNO-73621; Pyrimidine catabolism.
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:0004159; F:dihydropyrimidine dehydrogenase (NAD+) activity; IDA:RGD.
DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI: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: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:0006248; P:CMP catabolic process; ISO:RGD.
DR GO; GO:0006249; P:dCMP catabolic process; ISO:RGD.
DR GO; GO:0046079; P:dUMP catabolic process; ISO:RGD.
DR GO; GO:0006145; P:purine nucleobase catabolic process; ISO:RGD.
DR GO; GO:0006208; P:pyrimidine nucleobase catabolic process; 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:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0006214; P:thymidine catabolic process; ISS:UniProtKB.
DR GO; GO:0006210; P:thymine catabolic process; ISO:RGD.
DR GO; GO:0046050; P:UMP catabolic process; ISO:RGD.
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; IPR044512; DPYD.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR009051; Helical_ferredxn.
DR PANTHER; PTHR43073; PTHR43073; 1.
DR Pfam; PF01180; DHO_dh; 1.
DR Pfam; PF14691; Fer4_20; 1.
DR Pfam; PF07992; Pyr_redox_2; 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; Cytoplasm; FAD; Flavoprotein; FMN; Iron; Iron-sulfur;
KW Metal-binding; NADP; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1025
FT /note="Dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000327502"
FT DOMAIN 69..100
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 944..976
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 978..1007
FT /note="4Fe-4S ferredoxin-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT ACT_SITE 671
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 82
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 129
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 140
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 194..198
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 218..226
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 340..343
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 364..365
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 371
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 437..439
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 480..489
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 481..487
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 550
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 574..575
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 609
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 668..670
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 709
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 736..737
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 767
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 793..795
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 816..817
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 953
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 956
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 959
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 963
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 986
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 989
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 992
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 996
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT MOD_RES 384
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12882"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="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
