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Identification
HMDB Protein ID HMDBP00727
Secondary Accession Numbers
  • 6002
  • HMDBP04302
Name Dihydropyrimidine dehydrogenase [NADP(+)]
Synonyms
  1. DHPDHase
  2. DPD
  3. Dihydrothymine dehydrogenase
  4. Dihydrouracil dehydrogenase
Gene Name DPYD
Protein Type Unknown
Biological Properties
General Function Involved in electron carrier activity
Specific Function Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Pathways
  • Beta Ureidopropionase Deficiency
  • beta-alanine biosynthesis
  • beta-Alanine metabolism
  • beta-Alanine metabolism
  • Carnosinuria, carnosinemia
  • Dihydropyrimidinase Deficiency
  • Drug metabolism - other enzymes
  • GABA-Transaminase Deficiency
  • MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
  • Pantothenate and CoA biosynthesis
  • Pyrimidine metabolism
  • Pyrimidine metabolism
  • UMP Synthase Deficiency (Orotic Aciduria)
  • Ureidopropionase Deficiency
Reactions
Dihydrouracil + NADP → Uracil + NADPH details
Dihydrouracil + NADP → Uracil + NADPH + Hydrogen Ion details
Dihydrothymine + NADP → Thymine + NADPH + Hydrogen Ion details
Fluorouracil + NADPH + Hydrogen Ion → 5,6-Dihydro-5-fluorouracil + NADP details
GO Classification
Biological Process
beta-alanine biosynthetic process
purine nucleobase catabolic process
thymidine catabolic process
thymine catabolic process
UMP biosynthetic process
uracil catabolic process
Cellular Component
cytosol
Component
cell part
intracellular part
cytoplasm
Function
oxidoreductase activity, acting on the ch-ch group of donors
binding
catalytic activity
electron carrier activity
metal cluster binding
iron-sulfur cluster binding
dihydroorotate oxidase activity
oxidoreductase activity, acting on the ch-ch group of donors, quinone or related compound as acceptor
dihydroorotate dehydrogenase activity
oxidoreductase activity
Molecular Function
metal ion binding
NADP binding
oxidoreductase activity
4 iron, 4 sulfur cluster binding
protein homodimerization activity
dihydroorotate oxidase activity
dihydropyrimidine dehydrogenase (NADP+) activity
iron-sulfur cluster binding
flavin adenine dinucleotide binding
Process
metabolic process
nitrogen compound metabolic process
cellular nitrogen compound metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
nucleobase, nucleoside and nucleotide metabolic process
nucleoside phosphate metabolic process
nucleotide metabolic process
cellular aromatic compound metabolic process
cellular metabolic process
nucleobase metabolic process
pyrimidine base metabolic process
pyrimidine base biosynthetic process
'de novo' pyrimidine base biosynthetic process
pyrimidine nucleoside monophosphate biosynthetic process
pyrimidine ribonucleoside monophosphate biosynthetic process
ump biosynthetic process
oxidation reduction
pyrimidine nucleotide metabolic process
pyrimidine nucleotide biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 1
Locus 1p22
SNPs DPYD
Gene Sequence
>3078 bp
ATGGCCCCTGTGCTCAGTAAGGACTCGGCGGACATCGAGAGTATCCTGGCTTTAAATCCT
CGAACACAAACTCATGCAACTCTGTGTTCCACTTCGGCCAAGAAATTAGACAAGAAACAT
TGGAAAAGAAATCCTGATAAGAACTGCTTTAATTGTGAGAAGCTGGAGAATAATTTTGAT
GACATCAAGCACACGACTCTTGGTGAGCGAGGAGCTCTCCGAGAAGCAATGAGATGCCTG
AAATGTGCAGATGCCCCGTGTCAGAAGAGCTGTCCAACTAATCTTGATATTAAATCATTC
ATCACAAGTATTGCAAACAAGAACTATTATGGAGCTGCTAAGATGATATTTTCTGACAAC
CCACTTGGTCTGACTTGTGGAATGGTATGTCCAACCTCTGATCTTTGTGTAGGTGGATGC
AATTTATATGCCACTGAAGAGGGACCCATTAATATTGGTGGATTGCAGCAATTTGCTACT
GAGGTATTCAAAGCAATGAGTATCCCACAGATCAGAAATCCTTCGCTGCCTCCCCCAGAA
AAAATGTCTGAAGCCTATTCTGCAAAGATTGCTCTTTTTGGTGCTGGGCCTGCAAGTATA
AGTTGTGCTTCCTTTTTGGCTCGATTGGGGTACTCTGACATCACTATATTTGAAAAACAA
GAATATGTTGGTGGTTTAAGTACTTCTGAAATTCCTCAGTTCCGGCTGCCGTATGATGTA
GTGAATTTTGAGATTGAGCTAATGAAGGACCTTGGTGTAAAGATAATTTGCGGTAAAAGC
CTTTCAGTGAATGAAATGACTCTTAGCACTTTGAAAGAAAAAGGCTACAAAGCTGCTTTC
ATTGGAATAGGTTTGCCAGAACCCAATAAAGATGCCATCTTCCAAGGCCTGACGCAGGAC
CAGGGGTTTTATACATCCAAAGACTTTTTGCCACTTGTAGCCAAAGGCAGTAAAGCAGGA
ATGTGCGCCTGTCACTCTCCATTGCCATCGATACGGGGAGTCGTGATCGTACTTGGAGCT
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
Protein Properties
Number of Residues 1025
Molecular Weight 111400.32
Theoretical pI 7.05
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Dihydropyrimidine dehydrogenase [NADP+]
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRNCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
GenBank ID Protein 6729338
UniProtKB/Swiss-Prot ID Q12882
UniProtKB/Swiss-Prot Entry Name DPYD_HUMAN
PDB IDs Not Available
GenBank Gene ID AB003063
GeneCard ID DPYD
GenAtlas ID DPYD
HGNC ID HGNC:3012
References
General References
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  7. 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. [PubMed:8083224 ]
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