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 24-JUL-2013, entry version 143. 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 MASS SPECTROMETRY. 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 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 [14] 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 [15] 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: 5,6-dihydrouracil + NADP(+) = uracil + NADPH. CC -!- COFACTOR: Binds 2 FAD. CC -!- COFACTOR: Binds 2 FMN. CC -!- COFACTOR: Binds 4 4Fe-4S clusters. Contains approximately 16 iron CC atoms per subunit (By similarity). CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis. CC -!- SUBUNIT: Homodimer. 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. Note=The disease is caused by mutations affecting CC the gene represented in this entry. CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family. CC -!- SIMILARITY: Contains 3 4Fe-4S ferredoxin-type domains. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DPYD"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; AL356457; CAH70570.1; -; Genomic_DNA. DR EMBL; AC091608; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; AC093576; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; AC099787; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; AC114878; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; AC138135; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; BX908805; CAH70570.1; JOINED; Genomic_DNA. DR EMBL; BX908805; CAI15125.1; -; Genomic_DNA. DR EMBL; AC091608; CAI15125.1; JOINED; Genomic_DNA. DR EMBL; AC093576; CAI15125.1; JOINED; Genomic_DNA. DR EMBL; AC099787; CAI15125.1; JOINED; Genomic_DNA. DR EMBL; AC114878; CAI15125.1; JOINED; Genomic_DNA. DR EMBL; AC138135; CAI15125.1; JOINED; Genomic_DNA. DR EMBL; AL356457; CAI15125.1; JOINED; 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 IPI; IPI00029772; -. DR IPI; IPI00095889; -. DR PIR; A54718; A54718. DR RefSeq; NP_000101.2; NM_000110.3. DR RefSeq; NP_001153773.1; NM_001160301.1. DR UniGene; Hs.335034; -. DR ProteinModelPortal; Q12882; -. DR SMR; Q12882; 2-1019. DR IntAct; Q12882; 18. DR STRING; 9606.ENSP00000359211; -. DR PhosphoSite; Q12882; -. DR DMDM; 160332325; -. DR PaxDb; Q12882; -. DR PRIDE; Q12882; -. DR DNASU; 1806; -. DR Ensembl; ENST00000370192; ENSP00000359211; ENSG00000188641. DR GeneID; 1806; -. DR KEGG; hsa:1806; -. DR UCSC; uc001drv.3; human. DR CTD; 1806; -. DR GeneCards; GC01M097543; -. DR H-InvDB; HIX0000804; -. DR HGNC; HGNC:3012; DPYD. DR HPA; CAB033241; -. DR MIM; 274270; phenotype. DR MIM; 612779; gene. DR neXtProt; NX_Q12882; -. DR Orphanet; 240839; 5-fluorouracil toxicity. DR Orphanet; 240855; Capecitabine toxicity. DR Orphanet; 1675; Dihydropyrimidine dehydrogenase deficiency. DR Orphanet; 240955; Susceptibility to adverse reaction due to 5-fluorouracil treatment. DR Orphanet; 240963; Susceptibility to adverse reaction due to capecitabine treatment. DR PharmGKB; PA145; -. DR eggNOG; COG0167; -. DR HOVERGEN; HBG004351; -. DR InParanoid; Q12882; -. DR KO; K00207; -. DR OrthoDB; EOG44J2H8; -. DR Reactome; REACT_111217; Metabolism. DR UniPathway; UPA00131; -. DR BindingDB; Q12882; -. DR ChEMBL; CHEMBL3172; -. DR ChiTaRS; DPYD; human. DR DrugBank; DB01101; Capecitabine. DR DrugBank; DB00109; Enfuvirtide. DR GeneWiki; DPYD; -. DR GenomeRNAi; 1806; -. DR NextBio; 35501869; -. DR ArrayExpress; Q12882; -. DR Bgee; Q12882; -. DR CleanEx; HS_DPYD; -. DR Genevestigator; Q12882; -. 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:0004158; F:dihydroorotate oxidase activity; IEA:InterPro. DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) activity; IDA:UniProtKB. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050661; F:NADP binding; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. 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:0006214; P:thymidine catabolic process; IDA:UniProtKB. DR GO; GO:0006210; P:thymine catabolic process; IDA:UniProtKB. DR GO; GO:0006222; P:UMP biosynthetic process; IEA:InterPro. 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 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; IPR012135; Dihydroorotate_DH_1_2. DR InterPro; IPR012285; Fum_reductase_C. DR InterPro; IPR009051; Helical_ferredxn. DR Pfam; PF01180; DHO_dh; 1. DR SUPFAM; SSF46548; Helical_ferredxn; 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; Polymorphism; Reference proteome; KW 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 DOMAIN 944 976 4Fe-4S ferredoxin-type 2. FT DOMAIN 978 1007 4Fe-4S ferredoxin-type 3. FT NP_BIND 194 198 FAD (By similarity). FT NP_BIND 218 226 FAD (By similarity). FT NP_BIND 340 343 NADP (By similarity). FT NP_BIND 364 365 NADP (By similarity). FT NP_BIND 437 439 NADP (By similarity). FT NP_BIND 480 489 FAD (By similarity). FT NP_BIND 481 487 NADP (By similarity). FT NP_BIND 574 575 FMN (By similarity). FT NP_BIND 793 795 FMN (By similarity). FT NP_BIND 816 817 FMN (By similarity). FT REGION 668 670 Substrate binding (By similarity). FT REGION 736 737 Substrate binding (By similarity). FT ACT_SITE 671 671 Proton acceptor (By similarity). FT METAL 79 79 Iron-sulfur 1 (4Fe-4S) (By similarity). FT METAL 82 82 Iron-sulfur 1 (4Fe-4S) (By similarity). FT METAL 87 87 Iron-sulfur 1 (4Fe-4S) (By similarity). FT METAL 91 91 Iron-sulfur 2 (4Fe-4S) (By similarity). FT METAL 130 130 Iron-sulfur 2 (4Fe-4S) (By similarity). FT METAL 136 136 Iron-sulfur 2 (4Fe-4S) (By similarity). FT METAL 140 140 Iron-sulfur 1 (4Fe-4S) (By similarity). FT METAL 156 156 Iron-sulfur 2 (4Fe-4S) (By similarity). FT METAL 953 953 Iron-sulfur 3 (4Fe-4S) (By similarity). FT METAL 956 956 Iron-sulfur 3 (4Fe-4S) (By similarity). FT METAL 959 959 Iron-sulfur 3 (4Fe-4S) (By similarity). FT METAL 963 963 Iron-sulfur 3 (4Fe-4S) (By similarity). FT METAL 986 986 Iron-sulfur 4 (4Fe-4S) (By similarity). FT METAL 989 989 Iron-sulfur 4 (4Fe-4S) (By similarity). FT METAL 992 992 Iron-sulfur 4 (4Fe-4S) (By similarity). FT METAL 996 996 Iron-sulfur 4 (4Fe-4S) (By similarity). FT BINDING 129 129 FAD; via carbonyl oxygen (By similarity). FT BINDING 235 235 FAD (By similarity). FT BINDING 261 261 FAD; via amide nitrogen and carbonyl FT oxygen (By similarity). FT BINDING 371 371 NADP (By similarity). FT BINDING 550 550 FMN (By similarity). FT BINDING 609 609 Substrate (By similarity). FT BINDING 709 709 FMN (By similarity). FT BINDING 767 767 FMN; via amide nitrogen (By similarity). FT MOD_RES 384 384 N6-acetyllysine. FT VAR_SEQ 162 173 VFKAMSIPQIRN -> TLILAFSLMNHL (in isoform FT 2). FT /FTId=VSP_044929. FT VAR_SEQ 174 1025 Missing (in isoform 2). 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 /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 /FTId=VAR_005174. FT VARIANT 534 534 S -> N (in allele DPYD*4; low activity; FT dbSNP:rs1801158). FT /FTId=VAR_005175. FT VARIANT 543 543 I -> V (in allele DPYD*5; FT dbSNP:rs1801159). FT /FTId=VAR_005176. FT VARIANT 732 732 V -> I (in dbSNP:rs1801160). FT /FTId=VAR_014760. FT VARIANT 886 886 R -> H (in DPYDD; allele DPYD*9B; 25% of FT activity; dbSNP:rs1801267). 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 CONFLICT 845 845 E -> G (in Ref. 5; BAF83906). FT CONFLICT 910 910 N -> S (in Ref. 1; AAA57474). FT CONFLICT 1024 1024 V -> G (in Ref. 8; AAI31779). 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 //