DPYD_CAEEL
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 03-AUG-2022, entry version 163.
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 investigating
RT 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 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. {ECO:0000250,
CC 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; EC=1.3.1.2;
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms
CC 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}.
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DR EMBL; FO080672; CCD65682.1; -; Genomic_DNA.
DR PIR; T15616; T15616.
DR RefSeq; NP_508927.2; NM_076526.5.
DR AlphaFoldDB; Q18164; -.
DR SMR; Q18164; -.
DR BioGRID; 45751; 11.
DR DIP; DIP-25332N; -.
DR STRING; 6239.C25F6.3; -.
DR EPD; Q18164; -.
DR PaxDb; Q18164; -.
DR PeptideAtlas; Q18164; -.
DR EnsemblMetazoa; C25F6.3.1; C25F6.3.1; WBGene00016103.
DR GeneID; 180818; -.
DR KEGG; cel:CELE_C25F6.3; -.
DR CTD; 180818; -.
DR WormBase; C25F6.3; CE38489; WBGene00016103; dpyd-1.
DR eggNOG; KOG1799; Eukaryota.
DR GeneTree; ENSGT00500000044896; -.
DR HOGENOM; CLU_003991_0_0_1; -.
DR InParanoid; Q18164; -.
DR OMA; WPAIGKE; -.
DR OrthoDB; 592753at2759; -.
DR PhylomeDB; Q18164; -.
DR Reactome; R-CEL-73621; Pyrimidine catabolism.
DR SignaLink; Q18164; -.
DR UniPathway; UPA00131; -.
DR PRO; PR:Q18164; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00016103; Expressed in material anatomical entity and 4 other tissues.
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:0051536; F:iron-sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; 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; 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 3: Inferred from homology;
KW 4Fe-4S; FAD; Flavoprotein; FMN; Iron; Iron-sulfur; Metal-binding; NADP;
KW Nucleotide-binding; Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..1059
FT /note="Dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000079997"
FT DOMAIN 84..118
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 955..987
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 989..1019
FT /note="4Fe-4S ferredoxin-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT ACT_SITE 685
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 102
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 145
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 207..211
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 231..239
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 354..357
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 378..379
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 385
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 451..453
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 494..503
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 495..501
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 564
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 588..589
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 623
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 682..684
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 723
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 750..751
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 781
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 807..809
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 830..831
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 964
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 967
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 970
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 974
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 998
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1001
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1004
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1008
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="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
