DPYD_PONAB
ID DPYD_PONAB Reviewed; 1025 AA.
AC Q5R895;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:Q28943}.
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}.
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DR EMBL; CR859859; CAH92015.1; -; mRNA.
DR RefSeq; NP_001126169.1; NM_001132697.1.
DR AlphaFoldDB; Q5R895; -.
DR SMR; Q5R895; -.
DR STRING; 9601.ENSPPYP00000001308; -.
DR GeneID; 100173131; -.
DR KEGG; pon:100173131; -.
DR CTD; 1806; -.
DR eggNOG; KOG1799; Eukaryota.
DR InParanoid; Q5R895; -.
DR OrthoDB; 592753at2759; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000001595; 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; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW 4Fe-4S; Acetylation; Cytoplasm; FAD; Flavoprotein; FMN; Iron; Iron-sulfur;
KW Metal-binding; NADP; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1025
FT /note="Dihydropyrimidine dehydrogenase [NADP(+)]"
FT /id="PRO_0000327503"
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"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12882"
SQ SEQUENCE 1025 AA; 111468 MW; 39FAE483BA9983B6 CRC64;
MAPVLSKDSA DIESILALNP RTQTHATLRS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN
PLGLTCGMVC PTPDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPFLPPPE
KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD
QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF
IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN
EDEDQMVHLK ADVVISAFGS VLSDPKVKEA MSPIKFNRWG LPEVDPETMQ TSEAWVFAGG
DVVGLANTTV ESVNDGKQAS WYIHKYIQSQ YGASVSAKPE LPLFYTAIDL VDISVEMAGL
KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI VRGTTSGPMY
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI
ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS
TARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ
NIASSPHKRN CFIPKRPVPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY
MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS
VNPVC
