ID A0A3P8ZE51_ESOLU Unreviewed; 1034 AA.
AC A0A3P8ZE51;
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:ENSELUP00000026582.2};
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:ENSELUP00000026582.2, ECO:0000313|Proteomes:UP000265140};
RN [1] {ECO:0000313|Ensembl:ENSELUP00000026582.2, 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:ENSELUP00000026582.2}
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; A0A3P8ZE51; -.
DR Ensembl; ENSELUT00000018161.2; ENSELUP00000026582.2; ENSELUG00000002581.2.
DR GeneTree; ENSGT00500000044896; -.
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 953..985
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
FT DOMAIN 987..1016
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
SQ SEQUENCE 1034 AA; 112636 MW; 74B5F6CA683D945C CRC64;
MVNGHSARLL PLLPGSILAL 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
DIAMAAQEGI LLTAIDIPVA LDLEAGLHFI KHFHKSFPAM LCVWTLKGFL RSGNAIRPIT
LRAVSAIARA LPGFPILATG GIDSAESGLQ FLHAGASVLQ VCSAVQNQDF TLIEDYCLGL
KALLYLKSID ELQDWDGQSP PTIRHQKGKP VPRLEGLLGK SLPSFGPYLL EKKKVLADYK
EAVRDYVEKT TVVESSGTRT YTAKKPIPAV KDVIAGALKY IGAYGDLNNS EQVQAIIDEG
MCINCGKCYL TCNDSGYQAI SFDPKTHLPK VNDSCTGCTL CLSVCPVIDC IKMFARTTPY
VPKRGLPQAV MPVC
//
