ID A0A2Y9SGE7_PHYMC Unreviewed; 1025 AA.
AC A0A2Y9SGE7;
DT 12-SEP-2018, integrated into UniProtKB/TrEMBL.
DT 12-SEP-2018, sequence version 1.
DT 27-MAR-2024, entry version 28.
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|RefSeq:XP_023975370.1};
OS Physeter macrocephalus (Sperm whale) (Physeter catodon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Physeteridae; Physeter.
OX NCBI_TaxID=9755 {ECO:0000313|Proteomes:UP000248484, ECO:0000313|RefSeq:XP_023975370.1};
RN [1] {ECO:0000313|RefSeq:XP_023975370.1}
RP IDENTIFICATION.
RC TISSUE=Muscle {ECO:0000313|RefSeq:XP_023975370.1};
RG RefSeq;
RL Submitted (NOV-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 RefSeq; XP_023975370.1; XM_024119602.3.
DR AlphaFoldDB; A0A2Y9SGE7; -.
DR STRING; 9755.ENSPCTP00005002884; -.
DR Ensembl; ENSPCTT00005003164; ENSPCTP00005002884; ENSPCTG00005002078.
DR Ensembl; ENSPCTT00005003182; ENSPCTP00005002901; ENSPCTG00005002078.
DR Ensembl; ENSPCTT00005003224; ENSPCTP00005002939; ENSPCTG00005002078.
DR KEGG; pcad:102986090; -.
DR InParanoid; A0A2Y9SGE7; -.
DR OrthoDB; 1211169at2759; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000248484; Chromosome 4.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
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:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006248; P:CMP catabolic process; IEA:Ensembl.
DR GO; GO:0006249; P:dCMP catabolic process; IEA:Ensembl.
DR GO; GO:0046079; P:dUMP catabolic process; IEA:Ensembl.
DR GO; GO:0006145; P:purine nucleobase catabolic process; IEA:Ensembl.
DR GO; GO:0006214; P:thymidine catabolic process; IEA:Ensembl.
DR GO; GO:0006210; P:thymine catabolic process; IEA:Ensembl.
DR GO; GO:0046050; P:UMP catabolic process; IEA:Ensembl.
DR GO; GO:0006212; P:uracil catabolic process; IEA:Ensembl.
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; 2.
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:UP000248484};
KW Repeat {ECO:0000256|ARBA:ARBA00022737}.
FT DOMAIN 944..976
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
FT DOMAIN 978..1007
FT /note="4Fe-4S ferredoxin-type"
FT /evidence="ECO:0000259|PROSITE:PS51379"
SQ SEQUENCE 1025 AA; 111688 MW; 994A1935E03A73E0 CRC64;
MAPVLSKDVV DIESILALNP RTQSHATLHS TLAKKLAKKH WKRNPDKNCF NCEKLENNFD
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSISNKNYY GAAKMIFSDN
PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMNIPQ IRNHFLPPPE
KMPEAYSAKI ALLGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSISE IPQFRLPYNV
VNFEIELMKD LGVKIICGKS LSVNEITLST LKEEGYKAAF IGIGLPEPKK DHIFQGLTQD
QGFYTSKDFL PLVAKSSKAG MCACHSPLPS IRGAVIVLGA GDTAFDCATS ALRCGARRVF
IVFRKGFVHI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAVQFVR TEQDETGKWN
EDEDQIVRLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWD LPEVDPETMQ TSEPWVFAGG
DVVGMANTTV ESVNDGKQAS WYIHKYIQSQ YGASVSATPE LPLFYTPIDL VDISVEMAGL
KFTNPFGLAS ATPTTSSSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY
GPGQSSFLNI ELISEKTAAY WCQSVTELKT DFPDNIVIAS IMCSYNKNDW MELSRKAEAS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI
ARAAKEGGAD GVTATNTVSG LMGLKADGTP WPAVGTGKRT TYGGVSGTAV RPIALRAVST
IAHALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAVQ NQDFTVIQDY CTGLKALLYL
QSIEELQDWD GQSPPTESHQ KGKPVPRIAE LVGKKLPSFG PYLEQRKKII AEEKIRLKEQ
NATFPPLERK HFIPKKPIPT IKDVIGKALQ YLGTFGELSN LEQVVAVIDE EMCISCGKCY
MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIID CIRMVSRTTP YEPKRGLPLA
VNPVC
//
