Dihydropyrimidine dehydrogenase [NADP(+)]

Details

Name
Dihydropyrimidine dehydrogenase [NADP(+)]
Kind
protein
Synonyms
  • 1.3.1.2
  • DHPDHase
  • Dihydrothymine dehydrogenase
  • Dihydrouracil dehydrogenase
  • DPD
Gene Name
DPYD
UniProtKB Entry
Q12882Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037106|Dihydropyrimidine dehydrogenase [NADP(+)]
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRNCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
Number of residues
1025
Molecular Weight
111400.32
Theoretical pI
7.05
GO Classification
Functions
uracil binding
Processes
CMP catabolic process / dCMP catabolic process / dUMP catabolic process / UMP catabolic process
General Function
Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248)
Specific Function
4 iron, 4 sulfur cluster binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010674|Dihydropyrimidine dehydrogenase [NADP(+)] (DPYD)
ATGGCCCCTGTGCTCAGTAAGGACTCGGCGGACATCGAGAGTATCCTGGCTTTAAATCCT
CGAACACAAACTCATGCAACTCTGTGTTCCACTTCGGCCAAGAAATTAGACAAGAAACAT
TGGAAAAGAAATCCTGATAAGAACTGCTTTAATTGTGAGAAGCTGGAGAATAATTTTGAT
GACATCAAGCACACGACTCTTGGTGAGCGAGGAGCTCTCCGAGAAGCAATGAGATGCCTG
AAATGTGCAGATGCCCCGTGTCAGAAGAGCTGTCCAACTAATCTTGATATTAAATCATTC
ATCACAAGTATTGCAAACAAGAACTATTATGGAGCTGCTAAGATGATATTTTCTGACAAC
CCACTTGGTCTGACTTGTGGAATGGTATGTCCAACCTCTGATCTTTGTGTAGGTGGATGC
AATTTATATGCCACTGAAGAGGGACCCATTAATATTGGTGGATTGCAGCAATTTGCTACT
GAGGTATTCAAAGCAATGAGTATCCCACAGATCAGAAATCCTTCGCTGCCTCCCCCAGAA
AAAATGTCTGAAGCCTATTCTGCAAAGATTGCTCTTTTTGGTGCTGGGCCTGCAAGTATA
AGTTGTGCTTCCTTTTTGGCTCGATTGGGGTACTCTGACATCACTATATTTGAAAAACAA
GAATATGTTGGTGGTTTAAGTACTTCTGAAATTCCTCAGTTCCGGCTGCCGTATGATGTA
GTGAATTTTGAGATTGAGCTAATGAAGGACCTTGGTGTAAAGATAATTTGCGGTAAAAGC
CTTTCAGTGAATGAAATGACTCTTAGCACTTTGAAAGAAAAAGGCTACAAAGCTGCTTTC
ATTGGAATAGGTTTGCCAGAACCCAATAAAGATGCCATCTTCCAAGGCCTGACGCAGGAC
CAGGGGTTTTATACATCCAAAGACTTTTTGCCACTTGTAGCCAAAGGCAGTAAAGCAGGA
ATGTGCGCCTGTCACTCTCCATTGCCATCGATACGGGGAGTCGTGATTGTACTTGGAGCT
GGAGACACTGCCTTTGACTGTGCAACATCTGCTCTACGTTGTGGAGCTCGCCGTGTGTTC
ATCGTCTTCAGAAAAGGCTTTGTTAATATAAGAGCTGTCCCTGAGGAGATGGAACTTGCT
AAGGAAGAAAAGTGTGAATTTCTGCCATTCCTGTCCCCACGGAAGGTTATAGTAAAAGGT
GGGAGAATTGTTGCTATGCAGTTTGTTCGGACAGAGCAAGATGAAACTGGAAAATGGAAT
GAAGATGAAGATCAGATGGTCCATCTGAAAGCCGATGTGGTCATCAGTGCCTTTGGTTCA
GTTCTGAGTGATCCTAAAGTAAAAGAAGCCTTGAGCCCTATAAAATTTAACAGATGGGGT
CTCCCAGAAGTAGATCCAGAAACTATGCAAACTAGTGAAGCATGGGTATTTGCAGGTGGT
GATGTCGTTGGTTTGGCTAACACTACAGTGGAATCGGTGAATGATGGAAAGCAAGCTTCT
TGGTACATTCACAAATACGTACAGTCACAATATGGAGCTTCCGTTTCTGCCAAGCCTGAA
CTACCCCTCTTTTACACTCCTATTGATCTGGTGGACATTAGTGTAGAAATGGCCGGATTG
AAGTTTATAAATCCTTTTGGTCTTGCTAGCGCAACTCCAGCCACCAGCACATCAATGATT
CGAAGAGCTTTTGAAGCTGGATGGGGTTTTGCCCTCACCAAAACTTTCTCTCTTGATAAG
GACATTGTGACAAATGTTTCCCCCAGAATCATCCGGGGAACCACCTCTGGCCCCATGTAT
GGCCCTGGACAAAGCTCCTTTCTGAATATTGAGCTCATCAGTGAGAAAACGGCTGCATAT
TGGTGTCAAAGTGTCACTGAACTAAAGGCTGACTTTCCAGACAACATTGTGATTGCTAGC
ATTATGTGCAGTTACAATAAAAATGACTGGACGGAACTTGCCAAGAAGTCTGAGGATTCT
GGAGCAGATGCCCTGGAGTTAAATTTATCATGTCCACATGGCATGGGAGAAAGAGGAATG
GGCCTGGCCTGTGGGCAGGATCCAGAGCTGGTGCGGAACATCTGCCGCTGGGTTAGGCAA
GCTGTTCAGATTCCTTTTTTTGCCAAGCTGACCCCAAATGTCACTGATATTGTGAGCATC
GCAAGAGCTGCAAAGGAAGGTGGTGCCAATGGCGTTACAGCCACCAACACTGTCTCAGGT
CTGATGGGATTAAAATCTGATGGCACACCTTGGCCAGCAGTGGGGATTGCAAAGCGAACT
ACATATGGAGGAGTGTCTGGGACAGCAATCAGACCTATTGCTTTGAGAGCTGTGACCTCC
ATTGCTCGTGCTCTGCCTGGATTTCCCATTTTGGCTACTGGTGGAATTGACTCTGCTGAA
AGTGGTCTTCAGTTTCTCCATAGTGGTGCTTCCGTCCTCCAGGTATGCAGTGCCATTCAG
AATCAGGATTTCACTGTGATCGAAGACTACTGCACTGGCCTCAAAGCCCTGCTTTATCTG
AAAAGCATTGAAGAACTACAAGACTGGGATGGACAGAGTCCAGCTACTGTGAGTCACCAG
AAAGGGAAACCAGTTCCACGTATAGCTGAACTCATGGACAAGAAACTGCCAAGTTTTGGA
CCTTATCTGGAACAGCGCAAGAAAATCATAGCAGAAAACAAGATTAGACTGAAAGAACAA
AATGTAGCTTTTTCACCACTTAAGAGAAACTGTTTTATCCCCAAAAGGCCTATTCCTACC
ATCAAGGATGTAATAGGAAAAGCACTGCAGTACCTTGGAACATTTGGTGAATTGAGCAAC
GTAGAGCAAGTTGTGGCTATGATTGATGAAGAAATGTGTATCAACTGTGGTAAATGCTAC
ATGACCTGTAATGATTCTGGCTACCAGGCTATACAGTTTGATCCAGAAACCCACCTGCCC
ACCATAACCGACACTTGTACAGGCTGTACTCTGTGTCTCAGTGTTTGCCCTATTGTCGAC
TGCATCAAAATGGTTTCCAGGACAACACCTTATGAACCAAAGAGAGGCGTACCCTTATCT
GTGAATCCGGTGTGTTAA
Chromosome Location
1
Locus
1p21.3
External Identifiers
ResourceLink
UniProtKB IDQ12882
UniProtKB Entry NameDPYD_HUMAN
GenBank Protein ID558305
GenBank Gene IDU09178
GeneCard IDDPYD
GenAtlas IDDPYD
HGNC IDHGNC:3012
KEGG IDhsa:1806
NCBI Gene ID1806
General References
  1. Yokota H, Fernandez-Salguero P, Furuya H, Lin K, McBride OW, Podschun B, Schnackerz KD, Gonzalez FJ: cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. J Biol Chem. 1994 Sep 16;269(37):23192-6. [Article]
  2. Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB: Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Res. 1997 May 1;57(9):1660-3. [Article]
  3. Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T: Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett. 1998 Jan 9;122(1-2):107-13. [Article]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH: A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. J Inherit Metab Dis. 1996;19(5):645-54. [Article]
  8. Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ: Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin. Pharmacogenetics. 1997 Apr;7(2):161-3. [Article]
  9. Lu ZH, Zhang R, Diasio RB: Purification and characterization of dihydropyrimidine dehydrogenase from human liver. J Biol Chem. 1992 Aug 25;267(24):17102-9. [Article]
  10. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
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  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  13. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet. 1997 Dec;101(3):333-8. [Article]
  14. Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH: Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene. J Inherit Metab Dis. 1997 Jul;20(3):335-8. [Article]
  15. Ridge SA, Sludden J, Wei X, Sapone A, Brown O, Hardy S, Canney P, Fernandez-Salguero P, Gonzalez FJ, Cassidy J, McLeod HL: Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer. Br J Cancer. 1998;77(3):497-500. [Article]
  16. Ridge SA, Sludden J, Brown O, Robertson L, Wei X, Sapone A, Fernandez-Salguero PM, Gonzalez FJ, Vreken P, van Kuilenburg AB, van Gennip AH, McLeod HL: Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects. Br J Clin Pharmacol. 1998 Aug;46(2):151-6. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
(5S)-5-Iododihydro-2,4(1H,3H)-pyrimidinedioneexperimentalyestargetinhibitorDetails
NADPHexperimentalunknowntargetDetails
6-CarboxymethyluracilexperimentalyestargetinhibitorDetails
Flavin adenine dinucleotideapprovedyestargetinhibitorDetails
Flavin mononucleotideapproved, investigationalunknowntargetDetails
Uracilexperimental, investigationalyestargetmodulatorDetails
EniluracilinvestigationalyestargetmodulatorDetails
5-IodouracilexperimentalyestargetinhibitorDetails
FluorouracilapprovedunknownenzymesubstrateDetails
GimeracilapprovedyestargetinhibitorDetails
Tegafur-uracilapproved, investigationalnoenzymesubstrateDetails
Tegafur-uracilapproved, investigationalyestargetantagonistDetails
FluorouracilapprovedyestargetinhibitorDetails