DPYD_MOUSE
ID DPYD_MOUSE Reviewed; 1025 AA.
AC Q8CHR6;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)] {ECO:0000305};
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 {ECO:0000312|MGI:MGI:2139667};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-905, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-905, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; BC039699; AAH39699.1; -; mRNA.
DR CCDS; CCDS17797.1; -.
DR RefSeq; NP_740748.1; NM_170778.2.
DR AlphaFoldDB; Q8CHR6; -.
DR SMR; Q8CHR6; -.
DR STRING; 10090.ENSMUSP00000039429; -.
DR iPTMnet; Q8CHR6; -.
DR PhosphoSitePlus; Q8CHR6; -.
DR SwissPalm; Q8CHR6; -.
DR jPOST; Q8CHR6; -.
DR MaxQB; Q8CHR6; -.
DR PaxDb; Q8CHR6; -.
DR PeptideAtlas; Q8CHR6; -.
DR PRIDE; Q8CHR6; -.
DR ProteomicsDB; 279481; -.
DR Antibodypedia; 33674; 250 antibodies from 34 providers.
DR DNASU; 99586; -.
DR Ensembl; ENSMUST00000039177; ENSMUSP00000039429; ENSMUSG00000033308.
DR GeneID; 99586; -.
DR KEGG; mmu:99586; -.
DR UCSC; uc008rdh.1; mouse.
DR CTD; 1806; -.
DR MGI; MGI:2139667; Dpyd.
DR VEuPathDB; HostDB:ENSMUSG00000033308; -.
DR eggNOG; KOG1799; Eukaryota.
DR GeneTree; ENSGT00500000044896; -.
DR HOGENOM; CLU_003991_0_0_1; -.
DR InParanoid; Q8CHR6; -.
DR OMA; WPAIGKE; -.
DR OrthoDB; 592753at2759; -.
DR PhylomeDB; Q8CHR6; -.
DR TreeFam; TF105791; -.
DR Reactome; R-MMU-73621; Pyrimidine catabolism.
DR UniPathway; UPA00131; -.
DR BioGRID-ORCS; 99586; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Dpyd; mouse.
DR PRO; PR:Q8CHR6; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8CHR6; protein.
DR Bgee; ENSMUSG00000033308; Expressed in left lobe of liver and 215 other tissues.
DR ExpressionAtlas; Q8CHR6; baseline and differential.
DR Genevisible; Q8CHR6; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004159; F:dihydropyrimidine dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:MGI.
DR GO; GO:0071949; F:FAD binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; ISO:MGI.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0002058; F:uracil binding; ISO:MGI.
DR GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0007623; P:circadian rhythm; ISO:MGI.
DR GO; GO:0006248; P:CMP catabolic process; IDA:MGI.
DR GO; GO:0006249; P:dCMP catabolic process; IDA:MGI.
DR GO; GO:0046074; P:dTMP catabolic process; ISO:MGI.
DR GO; GO:0046079; P:dUMP catabolic process; IDA:MGI.
DR GO; GO:0006145; P:purine nucleobase catabolic process; ISO:MGI.
DR GO; GO:0006208; P:pyrimidine nucleobase catabolic process; IDA:MGI.
DR GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0006214; P:thymidine catabolic process; ISS:UniProtKB.
DR GO; GO:0006210; P:thymine catabolic process; ISO:MGI.
DR GO; GO:0046050; P:UMP catabolic process; IDA:MGI.
DR GO; GO:0006212; P:uracil catabolic process; ISS:UniProtKB.
DR GO; GO:0019860; P:uracil metabolic process; ISO:MGI.
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 1: Evidence at protein 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_0000327501"
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:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
SQ SEQUENCE 1025 AA; 111253 MW; AA1D1B3E3B72C504 CRC64;
MAGVLSRDAP DIESILALNP RVQAHATLRS TAAKKLDKKH WKRNTDKNCF TCEKLESNFD
DIKHTTLGER GALREAVRCL KCADAPCQKS CPTSLDIKSF ITSIANKNYY GAAKLIFSDN
PLGLTCGMVC PTSDLCVGGC NLHAAEEGPI NIGGLQQFAT EVFKAMNIPQ IRNPSLPPPE
HMPEAYSAKI ALFGAGPASI SCASFLARLG YSNITIFEKQ EYVGGLSTSE IPQFRLPYDV
VNFEIELMKD LGVKIICGKS LSTDEMTLSS LKENGYRAAF IGIGLPEPKK DHIFQGLTQV
QGFYTSKDFL PLVAKSSKTG MCACHSPLPS IRGAVIVLGA GDTAFDCATS ALRCGALRVF
IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKD GKIVAMQFVR TEQDETGNWV
EDEEQTVRLK ADVVISAFGS VLEDPKVKEA LSPIKFNRWG LPEVNPETMQ TSEPWVFAGG
DVVGMANTTV ESVNDGKQAS WYIHKHIQAQ YGTSVPSQPT MPLFYTPVDL VDISVEMAGL
RFPNPFGLAS ATPATSTPMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPLY
GPGQSSFLNI ELISEKTAAY WCHSVTELKA DFPDNILIAS IMCSYNKSDW MELSKMAEAS
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVRVPFFAKL TPNVTDIVSI
ARAAKEGGAD GVTATNTVSG LMGLKADGTP WPAVGIGRRT TYGGVSGTAI RPIALRAVTA
IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
KSIEELADWD GQSPPIISHQ KGKPVPRVAE LMGQKLPSFG PYLEQRKKII AASKIRQKDQ
NTACSPLQRK HFNSQKPIPA IKDVIGKSLQ YLGTFGEMSI MEQVVALIDE EMCINCGKCY
MTCNDSGYQA IQFDPETHLP TVSDTCTGCT LCLSVCPIMD CIRMVSRATP YQPKRGLPLA
VKPVC
