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Database: UniProt
Entry: Q18164
LinkDB: Q18164
Original site: Q18164 
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-JAN-2019, entry version 147.
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-1; ORFNames=C25F6.3;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   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 26:344-349(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       {ECO:0000250, ECO:0000269|PubMed:18612238}.
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   -!- 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       {ECO:0000305}.
DR   EMBL; FO080672; CCD65682.1; -; Genomic_DNA.
DR   PIR; T15616; T15616.
DR   RefSeq; NP_508927.2; NM_076526.5.
DR   UniGene; Cel.5583; -.
DR   ProteinModelPortal; Q18164; -.
DR   SMR; Q18164; -.
DR   BioGrid; 45751; 1.
DR   DIP; DIP-25332N; -.
DR   STRING; 6239.C25F6.3; -.
DR   EPD; Q18164; -.
DR   PaxDb; Q18164; -.
DR   PeptideAtlas; Q18164; -.
DR   PRIDE; Q18164; -.
DR   EnsemblMetazoa; C25F6.3; C25F6.3; WBGene00016103.
DR   GeneID; 180818; -.
DR   KEGG; cel:CELE_C25F6.3; -.
DR   CTD; 180818; -.
DR   WormBase; C25F6.3; CE38489; WBGene00016103; dpyd-1.
DR   eggNOG; KOG0399; Eukaryota.
DR   eggNOG; COG0167; LUCA.
DR   eggNOG; COG0493; LUCA.
DR   eggNOG; COG1146; LUCA.
DR   GeneTree; ENSGT00500000044896; -.
DR   HOGENOM; HOG000007797; -.
DR   InParanoid; Q18164; -.
DR   KO; K00207; -.
DR   OMA; HWKRNAD; -.
DR   OrthoDB; 592753at2759; -.
DR   PhylomeDB; Q18164; -.
DR   Reactome; R-CEL-73621; Pyrimidine catabolism.
DR   UniPathway; UPA00131; -.
DR   PRO; PR:Q18164; -.
DR   Proteomes; UP000001940; Chromosome X.
DR   Bgee; WBGene00016103; Expressed in 4 organ(s), highest expression level in material anatomical entity.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR   GO; GO:0004159; F:dihydrouracil dehydrogenase (NAD+) activity; IBA:GO_Central.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003954; F:NADH dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR   GO; GO:0002058; F:uracil binding; IBA:GO_Central.
DR   GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
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   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   3: Inferred from homology;
KW   4Fe-4S; Complete proteome; FAD; Flavoprotein; FMN; Iron; Iron-sulfur;
KW   Metal-binding; NADP; Nucleotide-binding; Oxidoreductase;
KW   Reference proteome; Repeat.
FT   CHAIN         1   1059       Dihydropyrimidine dehydrogenase
FT                                [NADP(+)].
FT                                /FTId=PRO_0000079997.
FT   DOMAIN       84    118       4Fe-4S ferredoxin-type 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      955    987       4Fe-4S ferredoxin-type 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      989   1019       4Fe-4S ferredoxin-type 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   NP_BIND     207    211       FAD. {ECO:0000250}.
FT   NP_BIND     231    239       FAD. {ECO:0000250}.
FT   NP_BIND     354    357       NADP. {ECO:0000250}.
FT   NP_BIND     378    379       NADP. {ECO:0000250}.
FT   NP_BIND     451    453       NADP. {ECO:0000250}.
FT   NP_BIND     494    503       FAD. {ECO:0000250}.
FT   NP_BIND     495    501       NADP. {ECO:0000250}.
FT   NP_BIND     588    589       FMN. {ECO:0000250}.
FT   NP_BIND     807    809       FMN. {ECO:0000250}.
FT   NP_BIND     830    831       FMN. {ECO:0000250}.
FT   REGION      682    684       Substrate binding. {ECO:0000250}.
FT   REGION      750    751       Substrate binding. {ECO:0000250}.
FT   ACT_SITE    685    685       Proton acceptor. {ECO:0000250}.
FT   METAL        94     94       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        97     97       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL       102    102       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL       106    106       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       145    145       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       151    151       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       155    155       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL       171    171       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       964    964       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       967    967       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       970    970       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       974    974       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       998    998       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL      1001   1001       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL      1004   1004       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL      1008   1008       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   BINDING     248    248       FAD. {ECO:0000250}.
FT   BINDING     274    274       FAD; via amide nitrogen and carbonyl
FT                                oxygen. {ECO:0000250}.
FT   BINDING     385    385       NADP. {ECO:0000250}.
FT   BINDING     564    564       FMN. {ECO:0000250}.
FT   BINDING     623    623       Substrate. {ECO:0000250}.
FT   BINDING     723    723       FMN. {ECO:0000250}.
FT   BINDING     781    781       FMN; via amide nitrogen. {ECO:0000250}.
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
//
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