DPYD_BOVIN
ID DPYD_BOVIN Reviewed; 1025 AA.
AC Q28007; Q9TRV4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)];
DE Short=DHPDHase;
DE Short=DPD;
DE EC=1.3.1.2 {ECO:0000250|UniProtKB:Q12882};
DE AltName: Full=Dihydrothymine dehydrogenase;
DE AltName: Full=Dihydrouracil dehydrogenase;
GN Name=DPYD;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8912928; DOI=10.3109/10425179609008450;
RA Albin N., Johnson M.R., Diasio R.B.;
RT "cDNA cloning of bovine liver dihydropyrimidine dehydrogenase.";
RL DNA Seq. 6:243-250(1996).
RN [2]
RP PROTEIN SEQUENCE OF 668-678, AND ACTIVITY REGULATION.
RC TISSUE=Liver;
RX PubMed=1939061; DOI=10.1016/s0021-9258(18)54881-x;
RA Porter D.J.T., Chestnut W.G., Taylor L.C.E., Merrill B.M., Spector T.;
RT "Inactivation of dihydropyrimidine dehydrogenase by 5-iodouracil.";
RL J. Biol. Chem. 266:19988-19994(1991).
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. {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 PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18095;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,6-dihydrothymine + NADP(+) = H(+) + NADPH + thymine;
CC Xref=Rhea:RHEA:58284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17821,
CC ChEBI:CHEBI:27468, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.2;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58286;
CC Evidence={ECO:0000250|UniProtKB:Q12882};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 2 FAD. {ECO:0000250|UniProtKB:Q28943};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 2 FMN. {ECO:0000250|UniProtKB:Q28943};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q28943};
CC Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms
CC per subunit. {ECO:0000250|UniProtKB:Q28943};
CC -!- ACTIVITY REGULATION: Inactivated by 5-iodouracil.
CC {ECO:0000269|PubMed:1939061}.
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000250|UniProtKB:Q12882}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12882}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q12882}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U20981; AAB40985.1; -; mRNA.
DR PIR; A44626; A44626.
DR RefSeq; NP_776466.1; NM_174041.2.
DR AlphaFoldDB; Q28007; -.
DR SMR; Q28007; -.
DR STRING; 9913.ENSBTAP00000007139; -.
DR ChEMBL; CHEMBL4630827; -.
DR PaxDb; Q28007; -.
DR PRIDE; Q28007; -.
DR GeneID; 281124; -.
DR KEGG; bta:281124; -.
DR CTD; 1806; -.
DR eggNOG; KOG1799; Eukaryota.
DR InParanoid; Q28007; -.
DR OrthoDB; 592753at2759; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000009136; Unplaced.
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:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
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; IEA:InterPro.
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 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Cytoplasm; Direct protein sequencing; FAD;
KW Flavoprotein; FMN; Iron; Iron-sulfur; Metal-binding; NADP;
KW Nucleotide-binding; Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..1025
FT /note="Dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000079996"
FT DOMAIN 69..100
FT /note="4Fe-4S ferredoxin-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 944..976
FT /note="4Fe-4S ferredoxin-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT DOMAIN 978..1007
FT /note="4Fe-4S ferredoxin-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711"
FT ACT_SITE 671
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 82
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 129
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 140
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 194..198
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 218..226
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 340..343
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 364..365
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 371
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 437..439
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 480..489
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 481..487
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 550
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 574..575
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 609
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 668..670
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 709
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 736..737
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 767
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 793..795
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 816..817
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250"
FT BINDING 953
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 956
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 959
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 963
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 986
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 989
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
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 996
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT MOD_RES 384
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12882"
SQ SEQUENCE 1025 AA; 111697 MW; 5B55F93A06C47F4F CRC64;
MAPVLSKDVA DIESILALNP RTQSRATLRS TLAKKLDKKH WKRNPDKNCF NCEKLENNFD
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSISNKNYY GAAKMIFSDN
PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQYAT EVFKAMNIPQ IRNPSLPPPE
KMPEAYSAKI ALLGAGPASI SCASFLARLG YNDITIFEKQ EYVGGISTSE IPQFRLPYDV
VNFEIELMKD LGVKIICGKS LSVNDITLST LKEEGYKAAF IGIGLPEPKK DHIFQGLTQD
QGFYTSKDFL PLVAKSSKAG MCACHSPLLS IRGTVIVLGA GDTAFDCATS ALRCGARRVF
IVFRKGFVNI RAVPEEVELA REEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN
EDGDQIACLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWD LPEVDPETMQ TSEPWVFAGG
DVVGIANTTV EAVNDGKQAS WYIHRYIQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAAL
KFTNPFGLAS ATPTTSSSMI RRAFEAGWAF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNRNDW MELSRKAEAS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVRIPFFAKL TPNVTDIVSI
ARAAKEGGAN GVTATNTVSG LMGLKADGTP WPAVGREKRT TYGGVSGTAI RPIALRAVTT
IARALPEFPI LATGGIDSAE SGLQFLHGGA SVLQVCSAIQ NQDFTIIQDY CTGLKALLYL
KSIEELQDWD GQSPATKSHQ KGKPVPCIAE LVGKKLPSFG PYLEKCKKII AEEKLRLKKE
NVTVLPLERN HFIPKKPIPS VKDVIGKALQ YLGTYGELNN TEQVVAVIDE EMCINCGKCY
MTCNDSGYQA IQFDPETHLP TVTDTCTGCT LCLSVCPIID CIKMVSRTTP YEPKRGLPLA
VNPVS
