DPYD

Protein identityUniProt · HPA

UniProt accession

Q12882

Gene

DPYD

Ensembl

ENSG00000188641

Chromosome

1

Canonical length

1025 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

Canonical amino-acid sequenceUniProt

1025 residues, UniProt reviewed canonical sequence.

>Q12882|DPYD
     1  MAPVLSKDSA DIESILALNP RTQTHATLCS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD
    61  DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN
   121  PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPSLPPPE
   181  KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV
   241  VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD
   301  QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF
   361  IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN
   421  EDEDQMVHLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWG LPEVDPETMQ TSEAWVFAGG
   481  DVVGLANTTV ESVNDGKQAS WYIHKYVQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAGL
   541  KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY
   601  GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS
   661  GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI
   721  ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS
   781  IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL
   841  KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ
   901  NVAFSPLKRN CFIPKRPIPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY
   961  MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS
  1021  VNPVC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DPYD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DPYD.

Disease | AllUniProt

Conditions DPYD is implicated in, by any mechanism.

• Dihydropyrimidine dehydrogenase deficiency (DPYDD) MIM:274270

Disease | GeneticClinVar

146 pathogenic / likely-pathogenic of 621 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dihydropyrimidine dehydrogenase deficiency
• DPYD-related disorder
• Inborn genetic diseases
• Fluorouracil response
• Neurodevelopmental delay

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1

gnomAD pLI

0

gnomAD missense Z

-0.22

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• CMP catabolic process
• dCMP catabolic process
• dUMP catabolic process
• pyrimidine nucleobase catabolic process
• thymine catabolic process
• UMP catabolic process
• uracil catabolic process
• xenobiotic catabolic process
• beta-alanine biosynthetic process
• purine nucleobase catabolic process
• thymidine catabolic process
• TMP catabolic process

Molecular functions

• 4 iron, 4 sulfur cluster binding
• flavin adenine dinucleotide binding
• metal ion binding
• NADP binding
• protein homodimerization activity
• dihydropyrimidine dehydrogenase (NADP+) activity
• uracil binding

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Dihydroorotate dehydrogenase, catalytic
• Alpha-helical ferredoxin
• Aldolase-type TIM barrel
• 4Fe-4S ferredoxin-type, iron-sulphur binding domain
• 4Fe-4S ferredoxin, iron-sulphur binding, conserved site
• FAD/NAD(P)-binding domain
• FAD/NAD(P)-binding domain superfamily
• Dihydroorotate dehydrogenase
• Pyridine nucleotide-disulphide oxidoreductase
• Dihydroprymidine dehydrogenase domain II
• Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster
• 4Fe-4S dicluster domain

KeywordsUniProt

• 4Fe-4S
• Acetylation
• Cytoplasm
• FAD
• Flavoprotein
• FMN
• Iron
• Iron-sulfur
• Metal-binding
• NADP
• Nucleotide-binding
• Oxidoreductase
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of DPYD in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GOPC