DPYD_CAEBR
ID DPYD_CAEBR Reviewed; 1053 AA.
AC A8XKG6;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Probable 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 {ECO:0000312|WormBase:CBG14689};
GN ORFNames=CBG14689 {ECO:0000312|WormBase:CBG14689};
OS Caenorhabditis briggsae.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6238;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AF16;
RX PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA Durbin R.M., Waterston R.H.;
RT "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT genomics.";
RL PLoS Biol. 1:166-192(2003).
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 (By similarity).
CC {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 -!- 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;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000250|UniProtKB:Q12882}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000255}.
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DR EMBL; HE600983; CAP33140.2; -; Genomic_DNA.
DR AlphaFoldDB; A8XKG6; -.
DR SMR; A8XKG6; -.
DR STRING; 6238.CBG14689; -.
DR WormBase; CBG14689; CBP49349; WBGene00035110; Cbr-dpyd-1.
DR eggNOG; KOG1799; Eukaryota.
DR HOGENOM; CLU_003991_0_0_1; -.
DR InParanoid; A8XKG6; -.
DR OMA; WPAIGKE; -.
DR OrthoDB; 592753at2759; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000008549; Chromosome X.
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; 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: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:0006210; P:thymine catabolic process; IBA:GO_Central.
DR GO; GO:0006212; P:uracil catabolic process; IBA:GO_Central.
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..1053
FT /note="Probable dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000355577"
FT DOMAIN 84..115
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 949..981
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 983..1013
FT /note="4Fe-4S ferredoxin-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT ACT_SITE 695
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 574
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 598..599
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 633
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 692..694
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 733
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 760..761
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 791
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 817..819
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 840..841
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 958
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 961
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
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 968
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
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 995
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
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 1002
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1053 AA; 114672 MW; AF22FB28C82FD43E CRC64;
MTPKPNTSNP NVGLPLLSKD SPDIESLLIL NPKVQSKANA VPSAVTKKNK HNWKRNEEKG
CGASCGESKL KNDFRDIKHT TLSERGALKE AMRCLKCADA PCQKSCPTQL DIKSFITSIS
NKNYYGAARA ILSDNPLGLT CGMICPTSDL CVGSCNLQAS EEGAINIGGL QQYACDVFKQ
MNVRQIVSKE VRENRNASHK EQIALIGCGP ASISCASFLA RLGYTDITIY EKRAYIGGLS
SAEIPQFRLP YDVVDFEIQL ARDVGVKIET NRSLCKEDIT LDKLKSQGAA AVFIGIGNPE
PKIDPLFEGL TIENGFYTSK NYLPAVAAAS KPGMCGCKRT PLPTMRGRVV VLGAGDTAMD
CATSALRCGA SRVTIAFRKG FTGIRAVPEE MEAAKEEKCE FLPFSAPRKI NVKDGRIVSI
EFNKTEQDDN GKWYEDEEQI VILKCDYVIS AFGSTLKEDT VLSALQPCKL NKWGGIEVDS
TTQQTSEAWV FAGGDVAGVA ETTVESVNDG KTLMDLTFKI QIAAWNMHRY IQAKHGNVLG
ETPELPKFFT PIDEVDISVD MCGVKFENPF GLASAPPTTS GPMCRRAFEQ GWGFILTKTY
GLDKDLVTNV SPRIVRGSTS GPLYGPNQGS FMNIELISEK SCEYWLQCIR ELKRDHPTKI
VVASIMCVYN KEDWIELATK SEAAGADILE LNLSCPHGMG EKGMGLACGQ SPEIVKEICR
WVRACVKIPF FPKMTPNITD VREIARAARD GGASGVTATN TVSSLMHMKA DGNAWPAIGN
TKRTTYGGMS GSAIRPIAMK AVSSIANELD GFPIMATGGI ESAETGLGFL MAGASVLQVC
SAVQNQDFTV VEDYCTGLKA LLYLSGAESL KEWDGQSPPV EKHQKGKPIL LQGQKNMPFF
GKFRDEREKL EALKLSESNL LDTDNYHFAS RPDTQVARVP TVEDVIEHEV AIIDHDMCIN
CGKCYMTCND SGYQAITFDA VTHQPHVTED DCTGCTLCYS VCPIPECIQM VPRKGPWKAP
KRGVKPTVEP GTPKVVKVDQ RGRVILESTG GMQ
