ID   DPYD_CAEEL              Reviewed;        1059 AA.
AC   Q18164;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   16-MAY-2006, sequence version 2.
DT   16-DEC-2008, entry version 68.
DE   RecName: Full=Dihydropyrimidine dehydrogenase [NADP+];
DE            Short=DHPDHase;
DE            Short=DPD;
DE            EC=1.3.1.2;
DE   AltName: Full=Dihydrouracil dehydrogenase;
DE   AltName: Full=Dihydrothymine dehydrogenase;
GN   Name=dpyd-1; ORFNames=C25F6.3;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Nematoda; Chromadorea; Rhabditida; Rhabditoidea;
OC   Rhabditidae; Peloderinae; Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   MEDLINE=99069613; PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for
RT   investigating biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   FUNCTION.
RX   PubMed=18612238;
RA   Kim S., Park D.-H., Shim J.;
RT   "Thymidylate synthase and dihydropyrimidine dehydrogenase levels are
RT   associated with response to 5-fluorouracil in Caenorhabditis
RT   elegans.";
RL   Mol. Cells 26:0-0(2008).
CC   -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC       reduction of uracil and thymine (By similarity). Involved in the
CC       degradation of the chemotherapeutic drug 5-fluorouracil.
CC   -!- CATALYTIC ACTIVITY: 5,6-dihydrouracil + NADP(+) = uracil + NADPH.
CC   -!- COFACTOR: Binds 2 4Fe-4S clusters (By similarity).
CC   -!- COFACTOR: FAD (By similarity).
CC   -!- COFACTOR: FMN (By similarity).
CC   -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC   -!- MISCELLANEOUS: Worms lacking dpyd-1 exhibit increased sensitivity
CC       (decreased survival) to the chemotherapeutic drug 5-fluorouracil.
CC   -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC   -!- SIMILARITY: Contains 3 4Fe-4S ferredoxin-type domains.
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DR   EMBL; U39742; AAK39195.2; -; Genomic_DNA.
DR   PIR; T15616; T15616.
DR   RefSeq; NP_508927.2; -.
DR   UniGene; Cel.5583; -.
DR   HSSP; Q28943; 1GTE.
DR   DIP; DIP:25332N; -.
DR   IntAct; Q18164; 1.
DR   Ensembl; C25F6.3; Caenorhabditis elegans.
DR   GeneID; 180818; -.
DR   KEGG; cel:C25F6.3; -.
DR   NMPDR; fig|6239.3.peg.23326; -.
DR   WormBase; WBGene00016103; dpyd-1.
DR   WormPep; C25F6.3; CE38489.
DR   NextBio; 911096; -.
DR   ArrayExpress; Q18164; -.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0004158; F:dihydroorotate oxidase activity; IEA:InterPro.
DR   GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) act...; ISS:UniProtKB.
DR   GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
DR   GO; GO:0050660; F:FAD binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006207; P:'de novo' pyrimidine base biosynthetic process; IEA:InterPro.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0006214; P:thymidine catabolic process; ISS:UniProtKB.
DR   GO; GO:0006212; P:uracil catabolic process; ISS:UniProtKB.
DR   InterPro; IPR001450; 4Fe4S_Fe_S_bd.
DR   InterPro; IPR000759; Adrndx_reductase.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR005720; DHO_DHase_1_core.
DR   InterPro; IPR001295; Dihydroorotate_DHase_core.
DR   InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR   InterPro; IPR012285; Fum_reductase_C.
DR   InterPro; IPR001327; Pyr_OxRdtase_NAD_bd.
DR   InterPro; IPR000103; Pyridine_nuc-diS_OxRdtase_2.
DR   Gene3D; G3DSA:3.20.20.70; Aldolase_TIM; 1.
DR   Gene3D; G3DSA:1.10.1060.10; Fum_reductase_C; 1.
DR   Pfam; PF01180; DHO_dh; 1.
DR   Pfam; PF00037; Fer4; 2.
DR   Pfam; PF00070; Pyr_redox; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   PRINTS; PR00353; 4FE4SFRDOXIN.
DR   PRINTS; PR00419; ADXRDTASE.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00469; PNDRDTASEII.
DR   ProDom; PD000139; FAD_pyr_redox; 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; Complete proteome; FAD; Flavoprotein; FMN; Iron; Iron-sulfur;
KW   Metal-binding; NADP; Oxidoreductase; Repeat.
FT   CHAIN         1   1059       Dihydropyrimidine dehydrogenase [NADP+].
FT                                /FTId=PRO_0000079997.
FT   DOMAIN       84    118       4Fe-4S ferredoxin-type 1.
FT   DOMAIN      955    987       4Fe-4S ferredoxin-type 2.
FT   DOMAIN      989   1019       4Fe-4S ferredoxin-type 3.
FT   METAL       964    964       Iron-sulfur 1 (4Fe-4S) (Potential).
FT   METAL       967    967       Iron-sulfur 1 (4Fe-4S) (Potential).
FT   METAL       970    970       Iron-sulfur 1 (4Fe-4S) (Potential).
FT   METAL       974    974       Iron-sulfur 1 (4Fe-4S) (Potential).
FT   METAL       998    998       Iron-sulfur 2 (4Fe-4S) (Potential).
FT   METAL      1001   1001       Iron-sulfur 2 (4Fe-4S) (Potential).
FT   METAL      1004   1004       Iron-sulfur 2 (4Fe-4S) (Potential).
FT   METAL      1008   1008       Iron-sulfur 2 (4Fe-4S) (Potential).
SQ   SEQUENCE   1059 AA;  115301 MW;  E5DDEEE1ED145262 CRC64;
     MTPKPNTTSP TNNLPLLSKD SPDIESLLIL NPKVQDKANA VPSAVTKKNK HNWKRNEEKG
     CGSTCGESKL KNDFRDIKHT TLSERGALKE AMRCLKCADA PCQKSCPTQL DVKSFITSIS
     NKNYYGAARQ ILSDNPLGLT CGMICPTSDL CVGSCNLQAS EEGAINIGGL QQYACDVFKQ
     MNVRQIVSKE VRENRNASHK EQVALIGCGP ASISCASFLA RLGYTDITIY EKRAYIGGLS
     SAEIPQFRLP YDVVDFEIQL ARDIGVQIET NRPLGKDGLT LAKLKEQGAA AVFIGIGNPE
     PKIDPLFEGL TIENGFYTSK NYLPAVAAAS KPGMCGCKRT PLPTMRGRVV VLGAGDTAMD
     CATSALRCGA SRVTIAFRKG FTGIRAVPEE MEAAKEEKCE FLPFSAPRKI NVKDGRIVSI
     EFNKTEQDDN GKWYEDEEQI VILKCDYVIS AFGSTLKEDA VLSALQPCQL NKWGGIEVDS
     TTQQTSEKWV FAGGDVAGVA ETTVESVNDG KIAAWNMHRY IQSLHGNQVS ETPELPQFFT
     PIDEVDISVD MCGVKFENPF GLASAPPTTS GPMCRRAFEQ GWGFILTKTY GLDKDLVTNV
     SPRIVRGSTS GPLYGPNQGS FMNIELISEK SCEYWLQCIR ELKRDHPTKI VIASIMCVYN
     KADWIELATK SEEAGADILE LNLSCPHGMG EKGMGLACGQ SPEIVKEICR WVRACVKIPF
     FPKMTPNITD VREIARAARD GGASGVTATN TVSSLMHMKA DGNAWPAIGS TKRTTYGGMS
     GSAIRPIAMK AVSSIANELD GFPIMATGGI ESAETGLGFL MAGASVLQVC SAVQNQDFTV
     VDDYCTGLKA LLYLSGAESL KNWDGQSPPI EKHQKGKPIL LQGQKKMPFF GKYRDEREKL
     EAIKLSESNL LDTENYHFAS RPDTQVSRVP TVEDVIGKAL PRIGPYVTLD NQEQKVAIID
     DDMCINCGKC YMTCNDSGYQ AITFDPVTHQ PHVTEDDCTG CTLCYSVCPI PECIEMVPRT
     GPWKAPKRGV KPSVEPGTPK VVKVDQRGRV ILDTTGGMQ
//