DPYD_DICDI
ID DPYD_DICDI Reviewed; 1009 AA.
AC Q55FT1; Q5ZQQ8;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 119.
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=pyd1; ORFNames=DDB_G0267966;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Gojkovic Z., Sandrini M.P.B., Piskur J.;
RT "Dihydropyrimidine dehydrogenases and the evolution of the pyrimidine
RT degradation pathway.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC reduction of uracil and thymine (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF545064; AAQ11981.1; -; mRNA.
DR EMBL; AAFI02000003; EAL73436.1; -; Genomic_DNA.
DR RefSeq; XP_647452.1; XM_642360.1.
DR AlphaFoldDB; Q55FT1; -.
DR SMR; Q55FT1; -.
DR STRING; 44689.DDB0231100; -.
DR PaxDb; Q55FT1; -.
DR EnsemblProtists; EAL73436; EAL73436; DDB_G0267966.
DR GeneID; 8616259; -.
DR KEGG; ddi:DDB_G0267966; -.
DR dictyBase; DDB_G0267966; pyd1.
DR eggNOG; KOG1799; Eukaryota.
DR HOGENOM; CLU_003991_0_0_1; -.
DR InParanoid; Q55FT1; -.
DR OMA; WPAIGKE; -.
DR PhylomeDB; Q55FT1; -.
DR Reactome; R-DDI-73621; Pyrimidine catabolism.
DR UniPathway; UPA00131; -.
DR PRO; PR:Q55FT1; -.
DR Proteomes; UP000002195; Chromosome 1.
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 2: Evidence at transcript level;
KW 4Fe-4S; Cytoplasm; FAD; Flavoprotein; FMN; Iron; Iron-sulfur;
KW Metal-binding; NADP; Nucleotide-binding; Oxidoreductase;
KW Reference proteome; Repeat.
FT CHAIN 1..1009
FT /note="Dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000327500"
FT DOMAIN 69..99
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 932..964
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 965..995
FT /note="4Fe-4S ferredoxin-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT ACT_SITE 669
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 86
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 90
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 129
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 135
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 139
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 193..197
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 217..225
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 234
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 339..342
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 363..364
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 370
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 436..438
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 478..486
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 479..484
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 548
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 572..573
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 607
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 666..668
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 707
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 734..735
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 765
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 791..793
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 814..815
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 941
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 944
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 947
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 951
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="4"
FT /evidence="ECO:0000250"
FT BINDING 977
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 980
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 984
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT CONFLICT 68
FT /note="E -> G (in Ref. 1; AAQ11981)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="R -> H (in Ref. 1; AAQ11981)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="S -> C (in Ref. 1; AAQ11981)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1009 AA; 110444 MW; CBC49049106B86B7 CRC64;
MTGHTGDVSQ VHDIEILALN PTVNKHATFK PTIVSKKDKE NWARLDHCKK GCELKNDFED
VKPTTLTERG ALFESARCLK CADAPCQKGC PTQLDIKSFI SSISTKNYYG AAKTIFSDNP
LGLTCGMVCP VSSLCQYGCN LAATEEGPIN IGGLQQFATE VFKKMNIPQI RDPSLTPLSQ
LPESYKAKIA LIGCGPTSIS CATFLGRLGY TDVTIFEKEQ YLGGLSSSEI PNYRLNYEVV
EFEIKLMKDL GVKVEYGKRL GENGFTVESL QKQGYEAIYL GIGMPEPKID PVFNELTSDQ
GFFSSKEFLP KVSKASKAGM CGCKSQLPQL NGRVIVLGAG DTAFDCATSA FRCGASRVTV
CFRRGFSDMR AVPEEVDIAK DERCEFLPYV LPKQVIKRDG KVVAMEFYKT EKGDDGNYSV
DEDQFFRVKC DYIISAFGSQ IGSVAESCSP LQFNKWGTAD IDPMTMTSKH AEWLFCGGDL
VGNGTTVEAV NDGKTASWNI HKYLQSLHGI PIPDGPPQLP NFFTPIDLVD ISVEMCGMKF
PNPFGLASAT PATSAAMIRR SFEQGWGFAV TKTFSLDKDL VTNVSPRIVR GTTSGHHFGP
GQGAFLNIEL ISEKTCHYWC KAIGELKRDF PDRIVIASIM CGFNKEDWTQ LAKMAEASGA
DGIELNLSCP HGMGEKGMGL ACGQDTELVF HICQWVRAAT RLPFFAKLTP NVTEIKEIAK
AAHDGGADGV TAINTVSGLM GLKGDSNAWP AIGDEKRTTY GGVSGNATRP IALRAVSSIR
KSLPDYPIMA TGGADSADAT IQFLHCGASV VQICSSVQNQ DFTVVQDYIT GLKTYLYMQS
REDLLQWDGQ SPPNEIINKN PKLKGLPKFG KYLLERNRID TEEKQNIDLQ KVKNPLVPSP
NPTHPVPSLK DQINRAIPRI GRHDDLKRDQ QVVALIDEDK CINCGKCYMT CNDSGYQAIK
FDGKTHIPLV TDLCTGCDLC LSVCPVPDCI TMVPRETIYV PDRGLTVQN
