ID A0A0G2K355_RAT Unreviewed; 1025 AA.
AC A0A0G2K355;
DT 22-JUL-2015, integrated into UniProtKB/TrEMBL.
DT 25-MAY-2022, sequence version 2.
DT 27-MAR-2024, entry version 41.
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:ENSRNOP00000072507.2,
GN ECO:0000313|RGD:621218};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000072507.2, ECO:0000313|Proteomes:UP000002494};
RN [1] {ECO:0000313|Ensembl:ENSRNOP00000072507.2, ECO:0000313|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000072507.2,
RC ECO:0000313|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RG Rat Genome Sequencing Project Consortium;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000313|Ensembl:ENSRNOP00000072507.2}
RP IDENTIFICATION.
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000072507.2};
RG Ensembl;
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 AlphaFoldDB; A0A0G2K355; -.
DR Ensembl; ENSRNOT00000086125.2; ENSRNOP00000072507.2; ENSRNOG00000017105.8.
DR RGD; 621218; Dpyd.
DR VEuPathDB; HostDB:ENSRNOG00000017105; -.
DR GeneTree; ENSGT00500000044896; -.
DR OMA; SIHCQLQ; -.
DR UniPathway; UPA00131; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000017105; Expressed in liver and 20 other cell types or tissues.
DR ExpressionAtlas; A0A0G2K355; baseline and differential.
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 1: Evidence at protein level;
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 Proteomics identification {ECO:0007829|PeptideAtlas:A0A0G2K355};
KW Reference proteome {ECO:0000313|Proteomes:UP000002494};
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; 111399 MW; C6F3FF472A3336BE CRC64;
MAGVLSRDAP DIESILALNP RIQAHATLRS TMAKKLDKKH WKRNTDKNCF TCEKLENNFD
DIKHTTLGER GALREAVRCL KCADAPCQKS CPTSLDIKSF ITSIANKNYY GAAKLIFSDN
PLGLTCGMVC PTSDLCVGGC NLHATEEGPI NIGGLQQFAT EVFKAMNIPQ IRSPLLPPPE
HMPEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
VNFEIELMKD LGVKIICGKS ISTDEMTLST LKENGYKAAF IGIGLPEPKK DHIFQGLTQV
QGFYTSKDFL PLVAKGSKPG MCACHSPLPS VRGAVIVLGA GDTAFDCATS ALRCGARRVF
IVFRKGFANI RAVPEEMELA KEEKCEFLPF LSPRKVIVKD GKIVGMQFVR TEQDETGNWV
EDEEQIVRLK ADVVISAFGS VLDDPKVIEA LSPIKFNRWG LPEVNPETMQ TSEPWVFAGG
DVVGMANTTV ESVNDGKQAS WYIHKYIQAQ YGALVPSQPT LPLFYTPVDL VDISVEMAGL
RFPNPFGLAS ATPATSTPMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPLY
GPGQSSFLNI ELISEKTAAY WCHSVTELKA DFPDNILIAS IMCSYNKNDW MELSKMAEAS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ SVRVPFFAKL TPNVTDIVSI
ARAAKEGGAD GVTATNTVSG LMGLKADGSP WPSVGSGKRT TYGGVSGTAI RPIALRAVTA
IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
KSIEELSDWD GQSPPTMSHQ KGKPVPHIAE LMGQKLPSFG PYLERRKKIL AASKIREKDQ
NRACSPLQRK HFNSQKPIPA IKDVIGKSLQ YLGTFGELNV MEQVVALIDE EMCINCGKCY
MTCNDSGYQA IQFDPETHLP TVSDTCTGCT LCLSVCPIMD CIRMVSRATP YEPKRGLPLA
VKPVC
//
