ID A0A3P8ZCV3_ESOLU Unreviewed; 1047 AA.
AC A0A3P8ZCV3;
DT 13-FEB-2019, integrated into UniProtKB/TrEMBL.
DT 02-DEC-2020, sequence version 2.
DT 27-MAR-2024, entry version 25.
DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)] {ECO:0000256|ARBA:ARBA00018247, ECO:0000256|RuleBase:RU364041};
DE Short=DHPDHase {ECO:0000256|RuleBase:RU364041};
DE Short=DPD {ECO:0000256|RuleBase:RU364041};
DE EC=1.3.1.2 {ECO:0000256|ARBA:ARBA00013004, ECO:0000256|RuleBase:RU364041};
DE AltName: Full=Dihydrothymine dehydrogenase {ECO:0000256|ARBA:ARBA00032722, ECO:0000256|RuleBase:RU364041};
DE AltName: Full=Dihydrouracil dehydrogenase {ECO:0000256|ARBA:ARBA00030119, ECO:0000256|RuleBase:RU364041};
GN Name=DPYD {ECO:0000313|Ensembl:ENSELUP00000026606.2};
OS Esox lucius (Northern pike).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Protacanthopterygii; Esociformes;
OC Esocidae; Esox.
OX NCBI_TaxID=8010 {ECO:0000313|Ensembl:ENSELUP00000026606.2, ECO:0000313|Proteomes:UP000265140};
RN [1] {ECO:0000313|Ensembl:ENSELUP00000026606.2, ECO:0000313|Proteomes:UP000265140}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=25069045;
RA Rondeau E.B., Minkley D.R., Leong J.S., Messmer A.M., Jantzen J.R.,
RA von Schalburg K.R., Lemon C., Bird N.H., Koop B.F.;
RT "The genome and linkage map of the northern pike (Esox lucius): conserved
RT synteny revealed between the salmonid sister group and the Neoteleostei.";
RL PLoS ONE 9:e102089-e102089(2014).
RN [2] {ECO:0000313|Ensembl:ENSELUP00000026606.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
CC -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC reduction of uracil and thymine. {ECO:0000256|RuleBase:RU364041}.
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:0000256|ARBA:ARBA00033676};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58286;
CC Evidence={ECO:0000256|ARBA:ARBA00033676};
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:0000256|ARBA:ARBA00033654};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18095;
CC Evidence={ECO:0000256|ARBA:ARBA00033654};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|ARBA:ARBA00001974,
CC ECO:0000256|RuleBase:RU364041};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000256|ARBA:ARBA00001917,
CC ECO:0000256|RuleBase:RU364041};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000256|RuleBase:RU364041};
CC Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms
CC per subunit. {ECO:0000256|RuleBase:RU364041};
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000256|ARBA:ARBA00004668, ECO:0000256|RuleBase:RU364041}.
CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC {ECO:0000256|ARBA:ARBA00010804, ECO:0000256|RuleBase:RU364041}.
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DR AlphaFoldDB; A0A3P8ZCV3; -.
DR Ensembl; ENSELUT00000018092.2; ENSELUP00000026606.2; ENSELUG00000002581.2.
DR GeneTree; ENSGT00500000044896; -.
DR InParanoid; A0A3P8ZCV3; -.
DR OMA; KMAIANY; -.
DR OrthoDB; 1211169at2759; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000265140; LG21.
DR Bgee; ENSELUG00000002581; Expressed in liver and 15 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
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 CDD; cd02940; DHPD_FMN; 1.
DR Gene3D; 3.30.70.20; -; 1.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR Gene3D; 1.10.1060.10; Alpha-helical ferredoxin; 1.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 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_cat.
DR InterPro; IPR028261; DPD_II.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR009051; Helical_ferredxn.
DR PANTHER; PTHR43073; DIHYDROPYRIMIDINE DEHYDROGENASE [NADP(+)]; 1.
DR PANTHER; PTHR43073:SF2; DIHYDROPYRIMIDINE DEHYDROGENASE [NADP(+)]; 1.
DR Pfam; PF01180; DHO_dh; 1.
DR Pfam; PF14691; Fer4_20; 1.
DR Pfam; PF14697; Fer4_21; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR PRINTS; PR00419; ADXRDTASE.
DR SUPFAM; SSF54862; 4Fe-4S ferredoxins; 1.
DR SUPFAM; SSF46548; alpha-helical ferredoxin; 1.
DR SUPFAM; SSF51395; FMN-linked oxidoreductases; 1.
DR SUPFAM; SSF51971; Nucleotide-binding domain; 1.
DR PROSITE; PS00198; 4FE4S_FER_1; 1.
DR PROSITE; PS51379; 4FE4S_FER_2; 2.
PE 3: Inferred from homology;
KW 4Fe-4S {ECO:0000256|ARBA:ARBA00022485, ECO:0000256|RuleBase:RU364041};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|RuleBase:RU364041};
KW Flavoprotein {ECO:0000256|RuleBase:RU364041};
KW FMN {ECO:0000256|ARBA:ARBA00022643, ECO:0000256|RuleBase:RU364041};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|RuleBase:RU364041};
KW Iron-sulfur {ECO:0000256|ARBA:ARBA00023014};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW NADP {ECO:0000256|RuleBase:RU364041};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|RuleBase:RU364041};
KW Reference proteome {ECO:0000313|Proteomes:UP000265140};
KW Repeat {ECO:0000256|ARBA:ARBA00022737}.
FT DOMAIN 949..981
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
FT DOMAIN 983..1012
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
SQ SEQUENCE 1047 AA; 113870 MW; 3AA7DD50EC522C3D CRC64;
MEMSRMLSKD LPDIESILAL NPRVKSHADI HSTASKKAEK KHWKRNPEKS CDSCLDLENN
FDDIKHTTLS ERGALREAMR CLKCADAPCQ KSCPTNLDIK SFITSIANKN YYGAAKSILS
DNPLGLTCGM VCPTSDLCVG GCNLYASEEG PINIGGLQQF ATEIFSKMGI PQVRNPALPA
PDQMPDSFHS KIALIGCGPA SISCASFLAR LGYDDITIFE KQKWIGGLSS AEIPQFRLPY
EVVNFEVELM KDLGVKVVCE KALGQDGMTL LSLREEGYKA VFIGIGLPQA NRHKIFDGLT
IDQGFYTSKD FLPLVAKASK TGMCSCKSSL PELCGTVIVL GAGDTAFDCA TSALRCGAKR
VFVVFRKGFT NIRAVPEEME LAKEEKCEFM PFLSPREVTM KAGRVAGMEF CRTEQTDDGD
WIEDEDQIIR LKANYIISAF GSMLNDPKVK EALAPVRLNR WGLPELDSDS MQTSEPWAFA
GGDVAGLANT TVESVNDGKQ ASWHMHKYLQ YLHGQTVPSV PQLPLFYCAI DSVDISVEMC
GIRFPNPFGL ASAPPTTSTA MIRRAFMEGW GFALTKTFSL DKDLVTNVSP RIVRGTTSGP
LFGPGQSSFL NIELISEKTA AYWCQSVTEL KADFPDNVII SSIMCSYNKA DWTELAQMAE
ASGADALELN LSCPHGMGER GMGLACGQDT ELVRNICRWV RKAVRIPFFA KLTPNVTDIV
DIAMAAQEGG ADGVTATNTV SGLMGLRADG TPWPGVGREK RTTYGGVSGN AIRPITLRAV
SAIARALPGF PILATGGIDS AESGLQFLHA GASVLQVCSA VQNQDFTLIE DYCLGLKALL
YLKSIDELQD WDGQSPPTIR HQKGKPVPRL EGLLGKSLPS FGPYLLEKKK VLADYKEAVR
DYVEKTTVVE SSGTRTYTAK KPIPAVKDVI AGALKYIGAY GDLNNSEQVQ AIIDEGMCIN
CGKCYLTCND SGYQAISFDP KTHLPKVNDS CTGCTLCLSV CPVIDCIKMF ARTTPYVPKR
GLPQAVMPAL IMRVKGGSKM EWKGREK
//
