GenomeNet

Database: UniProt
Entry: Q12882
LinkDB: Q12882
Original site: Q12882 
ID   DPYD_HUMAN              Reviewed;        1025 AA.
AC   Q12882; A2RRQ2; A2RRQ3; A8K5A2; A8MWG9; B1AN21; E9PFN1; Q16694;
AC   Q16761; Q32NB0; Q96HL6; Q96TH1;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 2.
DT   13-FEB-2019, entry version 190.
DE   RecName: Full=Dihydropyrimidine dehydrogenase [NADP(+)];
DE            Short=DHPDHase;
DE            Short=DPD;
DE            EC=1.3.1.2;
DE   AltName: Full=Dihydrothymine dehydrogenase;
DE   AltName: Full=Dihydrouracil dehydrogenase;
DE   Flags: Precursor;
GN   Name=DPYD;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=8083224;
RA   Yokota H., Fernandez-Salguero P., Furuya H., Lin K., McBride O.W.,
RA   Podschun B., Schnackerz K.D., Gonzalez F.J.;
RT   "cDNA cloning and chromosome mapping of human dihydropyrimidine
RT   dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and
RT   congenital thymine uraciluria.";
RL   J. Biol. Chem. 269:23192-23196(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9135003;
RA   Johnson M.R., Wang K., Tillmanns S., Albin N., Diasio R.B.;
RT   "Structural organization of the human dihydropyrimidine dehydrogenase
RT   gene.";
RL   Cancer Res. 57:1660-1663(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9464498; DOI=10.1016/S0304-3835(97)00377-7;
RA   Ogura K., Nishiyama T., Takubo H., Kato A., Okuda H., Arakawa K.,
RA   Fukushima M., Nagayama S., Kawaguchi Y., Watabe T.;
RT   "Suicidal inactivation of human dihydropyrimidine dehydrogenase by
RT   (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine.";
RL   Cancer Lett. 122:107-113(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT DPYDD
RP   ARG-29.
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT DPYDD
RP   ARG-29.
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
RP   VARIANTS VAL-543 AND ILE-732.
RC   TISSUE=Skin, and Uterus;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635.
RC   TISSUE=Liver;
RX   PubMed=8892022; DOI=10.1007/BF01799841;
RA   Vreken P., van Kuilenburg A.B.P., Meinsma R., Smit G.P.A.,
RA   Bakker H.D., de Abreu R.A., van Gennip A.H.;
RT   "A point mutation in an invariant splice donor site leads to exon
RT   skipping in two unrelated Dutch patients with dihydropyrimidine
RT   dehydrogenase deficiency.";
RL   J. Inherit. Metab. Dis. 19:645-654(1996).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635.
RX   PubMed=9170156;
RA   Fernandez-Salguero P.M., Sapone A., Wei X., Holt J.R., Jones S.,
RA   Idle J.R., Gonzalez F.J.;
RT   "Lack of correlation between phenotype and genotype for the
RT   polymorphically expressed dihydropyrimidine dehydrogenase in a family
RT   of Pakistani origin.";
RL   Pharmacogenetics 7:161-163(1997).
RN   [11]
RP   CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Liver;
RX   PubMed=1512248;
RA   Lu Z.-H., Zhang R., Diasio R.B.;
RT   "Purification and characterization of dihydropyrimidine dehydrogenase
RT   from human liver.";
RL   J. Biol. Chem. 267:17102-17109(1992).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-384, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA   Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA   Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-
RT   terminal acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-905, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [16]
RP   VARIANTS DPYDD ARG-29; TRP-235 AND HIS-886.
RX   PubMed=9439663; DOI=10.1007/s004390050637;
RA   Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.;
RT   "Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and
RT   expression of missense mutations C29R, R886H and R235W.";
RL   Hum. Genet. 101:333-338(1997).
RN   [17]
RP   VARIANTS DPYDD ARG-29; TRP-235 AND HIS-886.
RX   PubMed=9266349; DOI=10.1023/A:1005357307122;
RA   Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.;
RT   "Identification of novel point mutations in the dihydropyrimidine
RT   dehydrogenase gene.";
RL   J. Inherit. Metab. Dis. 20:335-338(1997).
RN   [18]
RP   VARIANTS ASN-534 AND VAL-543.
RX   PubMed=9472650; DOI=10.1038/bjc.1998.79;
RA   Ridge S.A., Sludden J., Wei X., Sapone A., Brown O., Hardy S.,
RA   Canney P., Fernandez-Salguero P., Gonzalez F.J., Cassidy J.,
RA   McLeod H.L.;
RT   "Dihydropyrimidine dehydrogenase pharmacogenetics in patients with
RT   colorectal cancer.";
RL   Br. J. Cancer 77:497-500(1998).
RN   [19]
RP   VARIANTS ASN-534; VAL-543 AND ILE-732.
RX   PubMed=9723824; DOI=10.1046/j.1365-2125.1998.00751.x;
RA   Ridge S.A., Sludden J., Brown O., Robertson L., Wei X., Sapone A.,
RA   Fernandez-Salguero P.M., Gonzalez F.J., Vreken P.,
RA   van Kuilenburg A.B., van Gennip A.H., McLeod H.L.;
RT   "Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian
RT   subjects.";
RL   Br. J. Clin. Pharmacol. 46:151-156(1998).
RN   [20]
RP   VARIANT [LARGE SCALE ANALYSIS] ARG-29.
RX   PubMed=18987736; DOI=10.1038/nature07485;
RA   Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA   Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA   Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA   Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA   Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA   Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA   Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J.,
RA   Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C.,
RA   Graubert T.A., DiPersio J.F., Wilson R.K.;
RT   "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT   genome.";
RL   Nature 456:66-72(2008).
CC   -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the
CC       reduction of uracil and thymine. Also involved the degradation of
CC       the chemotherapeutic drug 5-fluorouracil.
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;
CC         EC=1.3.1.2;
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC       Note=Binds 2 FAD.;
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC       Note=Binds 2 FMN.;
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250};
CC       Note=Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron
CC       atoms per subunit. {ECO:0000250};
CC   -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC   -!- SUBUNIT: Homodimer.
CC   -!- INTERACTION:
CC       Q9HD26:GOPC; NbExp=3; IntAct=EBI-2839838, EBI-349832;
CC       Q9BS40:LXN; NbExp=3; IntAct=EBI-2839838, EBI-1044504;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q12882-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q12882-2; Sequence=VSP_044929, VSP_044930;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Found in most tissues with greatest activity
CC       found in liver and peripheral blood mononuclear cells.
CC   -!- DISEASE: Dihydropyrimidine dehydrogenase deficiency (DPYDD)
CC       [MIM:274270]: A metabolic disorder with large phenotypic
CC       variability, ranging from no symptoms to a convulsive disorder
CC       with motor and mental retardation. It is characterized by
CC       persistent urinary excretion of excessive amounts of uracil,
CC       thymine and 5-hydroxymethyluracil. Patients suffering from this
CC       disease show a severe reaction to the anticancer drug 5-
CC       fluorouracil. {ECO:0000269|PubMed:14702039,
CC       ECO:0000269|PubMed:16710414, ECO:0000269|PubMed:9266349,
CC       ECO:0000269|PubMed:9439663}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family.
CC       {ECO:0000305}.
DR   EMBL; U09178; AAA57474.1; -; mRNA.
DR   EMBL; U20938; AAB51366.1; -; mRNA.
DR   EMBL; AB003063; BAA89789.1; -; mRNA.
DR   EMBL; BT006740; AAP35386.1; -; mRNA.
DR   EMBL; AK291217; BAF83906.1; -; mRNA.
DR   EMBL; AC091608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC099787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC114878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC138135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX908805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471097; EAW73002.1; -; Genomic_DNA.
DR   EMBL; BC008379; AAH08379.1; -; mRNA.
DR   EMBL; BC064027; AAH64027.1; -; mRNA.
DR   EMBL; BC108742; AAI08743.1; -; mRNA.
DR   EMBL; BC131777; AAI31778.1; -; mRNA.
DR   EMBL; BC131778; AAI31779.1; -; mRNA.
DR   EMBL; X95670; CAA64973.1; -; Genomic_DNA.
DR   EMBL; U57655; AAB07049.1; -; Genomic_DNA.
DR   CCDS; CCDS30777.1; -. [Q12882-1]
DR   CCDS; CCDS53346.1; -. [Q12882-2]
DR   PIR; A54718; A54718.
DR   RefSeq; NP_000101.2; NM_000110.3. [Q12882-1]
DR   RefSeq; NP_001153773.1; NM_001160301.1. [Q12882-2]
DR   UniGene; Hs.335034; -.
DR   ProteinModelPortal; Q12882; -.
DR   SMR; Q12882; -.
DR   BioGrid; 108140; 9.
DR   IntAct; Q12882; 20.
DR   STRING; 9606.ENSP00000359211; -.
DR   BindingDB; Q12882; -.
DR   ChEMBL; CHEMBL3172; -.
DR   DrugBank; DB03554; 5-Iodouracil.
DR   DrugBank; DB03048; 6-Carboxymethyluracil.
DR   DrugBank; DB01101; Capecitabine.
DR   DrugBank; DB03516; Eniluracil.
DR   DrugBank; DB03147; Flavin adenine dinucleotide.
DR   DrugBank; DB00544; Fluorouracil.
DR   DrugBank; DB02338; Nadph Dihydro-Nicotinamide-Adenine-Dinucleotidephosphate.
DR   DrugBank; DB03247; Riboflavin Monophosphate.
DR   DrugBank; DB03419; Uracil.
DR   CarbonylDB; Q12882; -.
DR   iPTMnet; Q12882; -.
DR   PhosphoSitePlus; Q12882; -.
DR   BioMuta; DPYD; -.
DR   DMDM; 160332325; -.
DR   EPD; Q12882; -.
DR   jPOST; Q12882; -.
DR   MaxQB; Q12882; -.
DR   PaxDb; Q12882; -.
DR   PeptideAtlas; Q12882; -.
DR   PRIDE; Q12882; -.
DR   ProteomicsDB; 58999; -.
DR   DNASU; 1806; -.
DR   Ensembl; ENST00000306031; ENSP00000307107; ENSG00000188641. [Q12882-2]
DR   Ensembl; ENST00000370192; ENSP00000359211; ENSG00000188641. [Q12882-1]
DR   GeneID; 1806; -.
DR   KEGG; hsa:1806; -.
DR   UCSC; uc001drv.4; human. [Q12882-1]
DR   CTD; 1806; -.
DR   DisGeNET; 1806; -.
DR   EuPathDB; HostDB:ENSG00000188641.12; -.
DR   GeneCards; DPYD; -.
DR   H-InvDB; HIX0000804; -.
DR   HGNC; HGNC:3012; DPYD.
DR   HPA; CAB033241; -.
DR   HPA; HPA045210; -.
DR   MalaCards; DPYD; -.
DR   MIM; 274270; phenotype.
DR   MIM; 612779; gene.
DR   neXtProt; NX_Q12882; -.
DR   OpenTargets; ENSG00000188641; -.
DR   Orphanet; 293948; 1p21.3 microdeletion syndrome.
DR   Orphanet; 240839; 5-fluorouracil toxicity.
DR   Orphanet; 1675; Dihydropyrimidine dehydrogenase deficiency.
DR   PharmGKB; PA145; -.
DR   eggNOG; KOG0399; Eukaryota.
DR   eggNOG; COG0167; LUCA.
DR   eggNOG; COG0493; LUCA.
DR   eggNOG; COG1146; LUCA.
DR   GeneTree; ENSGT00500000044896; -.
DR   HOGENOM; HOG000169491; -.
DR   HOVERGEN; HBG074715; -.
DR   InParanoid; Q12882; -.
DR   KO; K00207; -.
DR   OMA; HWKRNAD; -.
DR   OrthoDB; 1314811at2759; -.
DR   PhylomeDB; Q12882; -.
DR   TreeFam; TF105791; -.
DR   BioCyc; MetaCyc:HS06975-MONOMER; -.
DR   BRENDA; 1.3.1.2; 2681.
DR   Reactome; R-HSA-73621; Pyrimidine catabolism.
DR   SIGNOR; Q12882; -.
DR   UniPathway; UPA00131; -.
DR   ChiTaRS; DPYD; human.
DR   GeneWiki; DPYD; -.
DR   GenomeRNAi; 1806; -.
DR   PRO; PR:Q12882; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000188641; Expressed in 219 organ(s), highest expression level in germinal epithelium of ovary.
DR   Genevisible; Q12882; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR   GO; GO:0004159; F:dihydrouracil dehydrogenase (NAD+) activity; IBA:GO_Central.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003954; F:NADH dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0002058; F:uracil binding; IBA:GO_Central.
DR   GO; GO:0019483; P:beta-alanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006145; P:purine nucleobase catabolic process; IMP:UniProtKB.
DR   GO; GO:0006208; P:pyrimidine nucleobase catabolic process; IMP:UniProtKB.
DR   GO; GO:0046135; P:pyrimidine nucleoside catabolic process; TAS:Reactome.
DR   GO; GO:0006214; P:thymidine catabolic process; IDA:UniProtKB.
DR   GO; GO:0006210; P:thymine catabolic process; IDA:UniProtKB.
DR   GO; GO:0006212; P:uracil catabolic process; IDA:UniProtKB.
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; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR023753; FAD/NAD-binding_dom.
DR   InterPro; IPR009051; Helical_ferredxn.
DR   Pfam; PF01180; DHO_dh; 1.
DR   Pfam; PF14691; Fer4_20; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   SUPFAM; SSF46548; SSF46548; 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; Alternative splicing; Complete proteome;
KW   Cytoplasm; Direct protein sequencing; Disease mutation; FAD;
KW   Flavoprotein; FMN; Iron; Iron-sulfur; Metal-binding; NADP;
KW   Nucleotide-binding; Oxidoreductase; Phosphoprotein; Polymorphism;
KW   Reference proteome; Repeat.
FT   PROPEP        1      3
FT                                /FTId=PRO_0000021114.
FT   CHAIN         4   1025       Dihydropyrimidine dehydrogenase
FT                                [NADP(+)].
FT                                /FTId=PRO_0000021115.
FT   DOMAIN       69    100       4Fe-4S ferredoxin-type 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      944    976       4Fe-4S ferredoxin-type 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   DOMAIN      978   1007       4Fe-4S ferredoxin-type 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00711}.
FT   NP_BIND     194    198       FAD. {ECO:0000250}.
FT   NP_BIND     218    226       FAD. {ECO:0000250}.
FT   NP_BIND     340    343       NADP. {ECO:0000250}.
FT   NP_BIND     364    365       NADP. {ECO:0000250}.
FT   NP_BIND     437    439       NADP. {ECO:0000250}.
FT   NP_BIND     480    489       FAD. {ECO:0000250}.
FT   NP_BIND     481    487       NADP. {ECO:0000250}.
FT   NP_BIND     574    575       FMN. {ECO:0000250}.
FT   NP_BIND     793    795       FMN. {ECO:0000250}.
FT   NP_BIND     816    817       FMN. {ECO:0000250}.
FT   REGION      668    670       Substrate binding. {ECO:0000250}.
FT   REGION      736    737       Substrate binding. {ECO:0000250}.
FT   ACT_SITE    671    671       Proton acceptor. {ECO:0000250}.
FT   METAL        79     79       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        82     82       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        87     87       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL        91     91       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       130    130       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       136    136       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       140    140       Iron-sulfur 1 (4Fe-4S). {ECO:0000250}.
FT   METAL       156    156       Iron-sulfur 2 (4Fe-4S). {ECO:0000250}.
FT   METAL       953    953       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       956    956       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       959    959       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       963    963       Iron-sulfur 3 (4Fe-4S). {ECO:0000250}.
FT   METAL       986    986       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       989    989       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       992    992       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   METAL       996    996       Iron-sulfur 4 (4Fe-4S). {ECO:0000250}.
FT   BINDING     129    129       FAD; via carbonyl oxygen. {ECO:0000250}.
FT   BINDING     235    235       FAD. {ECO:0000250}.
FT   BINDING     261    261       FAD; via amide nitrogen and carbonyl
FT                                oxygen. {ECO:0000250}.
FT   BINDING     371    371       NADP. {ECO:0000250}.
FT   BINDING     550    550       FMN. {ECO:0000250}.
FT   BINDING     609    609       Substrate. {ECO:0000250}.
FT   BINDING     709    709       FMN. {ECO:0000250}.
FT   BINDING     767    767       FMN; via amide nitrogen. {ECO:0000250}.
FT   MOD_RES     384    384       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     905    905       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   VAR_SEQ     162    173       VFKAMSIPQIRN -> TLILAFSLMNHL (in isoform
FT                                2). {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|Ref.4}.
FT                                /FTId=VSP_044929.
FT   VAR_SEQ     174   1025       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|Ref.4}.
FT                                /FTId=VSP_044930.
FT   VARIANT      29     29       C -> R (in DPYDD; allele DPYD*9A and
FT                                allele DPYD*9B; loss of activity;
FT                                dbSNP:rs1801265).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|PubMed:16710414,
FT                                ECO:0000269|PubMed:18987736,
FT                                ECO:0000269|PubMed:9266349,
FT                                ECO:0000269|PubMed:9439663}.
FT                                /FTId=VAR_005173.
FT   VARIANT     166    166       M -> V (in dbSNP:rs2297595).
FT                                /FTId=VAR_054034.
FT   VARIANT     235    235       R -> W (in DPYDD; allele DPYD*8; loss of
FT                                activity; dbSNP:rs1801266).
FT                                {ECO:0000269|PubMed:9266349,
FT                                ECO:0000269|PubMed:9439663}.
FT                                /FTId=VAR_005174.
FT   VARIANT     534    534       S -> N (in allele DPYD*4;
FT                                dbSNP:rs1801158).
FT                                {ECO:0000269|PubMed:9472650,
FT                                ECO:0000269|PubMed:9723824}.
FT                                /FTId=VAR_005175.
FT   VARIANT     543    543       I -> V (in allele DPYD*5;
FT                                dbSNP:rs1801159).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:9472650,
FT                                ECO:0000269|PubMed:9723824}.
FT                                /FTId=VAR_005176.
FT   VARIANT     732    732       V -> I (in dbSNP:rs1801160).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:9723824}.
FT                                /FTId=VAR_014760.
FT   VARIANT     886    886       R -> H (in DPYDD; allele DPYD*9B; 25% of
FT                                activity; dbSNP:rs1801267).
FT                                {ECO:0000269|PubMed:9266349,
FT                                ECO:0000269|PubMed:9439663}.
FT                                /FTId=VAR_005177.
FT   VARIANT     995    995       V -> F (in allele DPYD*10; low activity;
FT                                dbSNP:rs1801268).
FT                                /FTId=VAR_005178.
FT   CONFLICT    131    131       P -> S (in Ref. 6; AAI08743).
FT                                {ECO:0000305}.
FT   CONFLICT    845    845       E -> G (in Ref. 5; BAF83906).
FT                                {ECO:0000305}.
FT   CONFLICT    910    910       N -> S (in Ref. 1; AAA57474).
FT                                {ECO:0000305}.
FT   CONFLICT   1024   1024       V -> G (in Ref. 8; AAI31779).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1025 AA;  111401 MW;  0201943955AB2C21 CRC64;
     MAPVLSKDSA DIESILALNP RTQTHATLCS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD
     DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN
     PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPSLPPPE
     KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
     VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD
     QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF
     IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN
     EDEDQMVHLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWG LPEVDPETMQ TSEAWVFAGG
     DVVGLANTTV ESVNDGKQAS WYIHKYVQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAGL
     KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY
     GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS
     GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI
     ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS
     IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
     KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ
     NVAFSPLKRN CFIPKRPIPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY
     MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS
     VNPVC
//
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