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UniProtKB/Swiss-Prot entry Q12882


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name DPYD_HUMAN
Primary accession number Q12882
Secondary accession numbers A2RRQ2 A2RRQ3 A8K5A2 A8MWG9 Q16694 Q16761 Q96TH1
Integrated into Swiss-Prot on November 1, 1997
Sequence was last modified on November 13, 2007 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 87)
Name and origin of the protein
Protein name Dihydropyrimidine dehydrogenase [NADP+] [Precursor]
Synonyms DHPDHase
DPD
EC 1.3.1.2
Dihydrouracil dehydrogenase
Dihydrothymine dehydrogenase
Gene name
Name: DPYD
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
PubMed=8083224 [NCBI, ExPASy, EBI, Israel, Japan]
Yokota H., Fernandez-Salguero P., Furuya H., Lin K., McBride O.W., Podschun B., Schnackerz K.D., Gonzalez F.J.;
"cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria.";
J. Biol. Chem. 269:23192-23196(1994).
[2]
NUCLEOTIDE SEQUENCE.
PubMed=9135003 [NCBI, ExPASy, EBI, Israel, Japan]
Johnson M.R., Wang K., Tillmanns S., Albin N., Diasio R.B.;
"Structural organization of the human dihydropyrimidine dehydrogenase gene.";
Cancer Res. 57:1660-1663(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/S0304-3835(97)00377-7; PubMed=9464498 [NCBI, ExPASy, EBI, Israel, Japan]
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. 122:107-113(1998).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-29.
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-543 AND ILE-732.
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635.
TISSUE=Liver;
DOI=10.1007/BF01799841; PubMed=8892022 [NCBI, ExPASy, EBI, Israel, Japan]
Vreken P., van Kuilenburg A.B.P., Meinsma R., Smit G.P.A., Bakker H.D., de Abreu R.A., van Gennip A.H.;
"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. 19:645-654(1996).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635.
PubMed=9170156 [NCBI, ExPASy, EBI, Israel, Japan]
Fernandez-Salguero P.M., Sapone A., Wei X., Holt J.R., Jones S., Idle J.R., Gonzalez F.J.;
"Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin.";
Pharmacogenetics 7:161-163(1997).
[9]
CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE.
TISSUE=Liver;
PubMed=1512248 [NCBI, ExPASy, EBI, Israel, Japan]
Lu Z.-H., Zhang R., Diasio R.B.;
"Purification and characterization of dihydropyrimidine dehydrogenase from human liver.";
J. Biol. Chem. 267:17102-17109(1992).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-577, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
[11]
VARIANTS ARG-29; TRP-235 AND HIS-886.
DOI=10.1007/s004390050637; PubMed=9439663 [NCBI, ExPASy, EBI, Israel, Japan]
Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.;
"Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W.";
Hum. Genet. 101:333-338(1997).
[12]
VARIANTS ARG-29; TRP-235 AND HIS-886.
DOI=10.1023/A:1005357307122; PubMed=9266349 [NCBI, ExPASy, EBI, Israel, Japan]
Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.;
"Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene.";
J. Inherit. Metab. Dis. 20:335-338(1997).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U09178; AAA57474.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U20938; AAB51366.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB003063; BAA89789.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK291217; BAF83906.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC091608; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
BC131777; AAI31778.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC131778; AAI31779.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X95670; CAA64973.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U57655; AAB07049.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A54718; A54718.
RefSeq NP_000101.2; -.
UniGene Hs.335034
3D structure databases
HSSP Q28943; 1GTE. [HSSP ENTRY / PDB]
SMR Q12882; 2-1017.
ModBase Q12882.
PTM databases
PhosphoSite Q12882; -.
Enzyme and pathway databases
Reactome REACT_1698; Nucleotide metabolism.
Organism-specific databases
H-InvDB HIX0000804; -.
HGNC HGNC:3012; DPYD.
GenAtlas DPYD.
MIM 274270; gene+phenotype. [NCBI / EBI]
Orphanet 1675; Dihydropyrimidine dehydrogenase deficiency.
PharmGKB PA145; -.
GeneCards Q12882.
Gene expression databases
ArrayExpress Q12882; -.
CleanEx HS_DPYD; -.
GermOnline ENSG00000188641; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0017113; Molecular function: dihydropyrimidine dehydrogenase (NADP+) activity (inferred from direct assay from UniProtKB).
GO:0004159; Molecular function: dihydrouracil dehydrogenase (NAD+) activity (inferred from experiment from Reactome).
GO:0050660; Molecular function: FAD binding (inferred from sequence or structural similarity from UniProtKB).
GO:0050661; Molecular function: NADP binding (inferred from sequence or structural similarity from UniProtKB).
GO:0042803; Molecular function: protein homodimerization activity (inferred from direct assay from UniProtKB).
GO:0006145; Biological process: purine base catabolic process (inferred from mutant phenotype from UniProtKB).
GO:0006214; Biological process: thymidine catabolic process (inferred from direct assay from UniProtKB).
GO:0006210; Biological process: thymine catabolic process (inferred from direct assay from UniProtKB).
GO:0006212; Biological process: uracil catabolic process (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001450; 4Fe4S_Fe_S_bd.
IPR000759; Adrndx_reductase.
IPR013785; Aldolase_TIM.
IPR005720; DHO_DHase_1_core.
IPR001295; Dihydroorotate_DHase_core.
IPR013027; FAD_pyr_nucl-diS_OxRdtase.
IPR012285; Fum_reductase_C.
IPR016040; NAD(P)-bd.
Graphical view of domain structure.
Gene3D G3DSA:3.20.20.70; Aldolase_TIM; 1.
G3DSA:1.10.1060.10; Fum_reductase_C; 1.
G3DSA:3.40.50.720; NAD(P)-bd; 1.
Pfam PF01180; DHO_dh; 1.
PF00037; Fer4; 2.
PF07992; Pyr_redox_2; 1.
Pfam graphical view of domain structure.
PRINTS PR00419; ADXRDTASE.
PR00368; FADPNR.
ProDom PD000139; FAD_pyr_redox; 1.
[Domain structure / List of seq. sharing at least 1 domain]
TIGRFAMs TIGR01037; pyrD_sub1_fam; 1.
PROSITE PS00198; 4FE4S_FER_1; 1.
PS51379; 4FE4S_FER_2; 3.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q12882.
Genome annotation databases
Ensembl ENSG00000188641; Homo sapiens. [Contig view]
GeneID 1806; -.
KEGG hsa:1806; -.
Phylogenomic databases
HOGENOM Q12882; -.
HOVERGEN Q12882; -.
Other
DrugBank DB01101; Capecitabine.
DB00109; Enfuvirtide.
SOURCE DPYD; Homo sapiens.
ProtoNet Q12882.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
4Fe-4S; Cytoplasm; Direct protein sequencing; Disease mutation; FAD; Flavoprotein; FMN; Iron; Iron-sulfur; Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; Repeat.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
PROPEP   1      3  3      PRO_0000021114
CHAIN   4   1025  1022     Dihydropyrimidine dehydrogenase [NADP+]. PRO_0000021115
DOMAIN   69    100  32     4Fe-4S ferredoxin-type 1. 
DOMAIN   944    976  33     4Fe-4S ferredoxin-type 2. 
DOMAIN   978   1007  30     4Fe-4S ferredoxin-type 3. 
NP_BIND   335    351  17     NADP (Potential). 
NP_BIND   471    481  11     FAD (Potential). 
REGION   661    678  18     Uracil binding (Potential). 
METAL   953    953        Iron-sulfur 1 (4Fe-4S) (Potential). 
METAL   956    956        Iron-sulfur 1 (4Fe-4S) (Potential). 
METAL   959    959        Iron-sulfur 1 (4Fe-4S) (Potential). 
METAL   963    963        Iron-sulfur 1 (4Fe-4S) (Potential). 
METAL   986    986        Iron-sulfur 2 (4Fe-4S) (Potential). 
METAL   989    989        Iron-sulfur 2 (4Fe-4S) (Potential). 
METAL   992    992        Iron-sulfur 2 (4Fe-4S) (Potential). 
METAL   996    996        Iron-sulfur 2 (4Fe-4S) (Potential). 
MOD_RES   577    577        Phosphoserine. 
VARIANT   29     29  1     C -> R (in allele DPYD*9A and allele DPYD*9B; loss of activity; dbSNP:rs1801265 [NCBI]). VAR_005173 [3D]
VARIANT   235    235  1     R -> W (in allele DPYD*8; loss of activity; dbSNP:rs1801266 [NCBI]). VAR_005174 [3D]
VARIANT   534    534  1     S -> N (in allele DPYD*4; low activity; dbSNP:rs1801158 [NCBI]). VAR_005175 [3D]
VARIANT   543    543  1     I -> V (in allele DPYD*5; dbSNP:rs1801159 [NCBI]). VAR_005176 [3D]
VARIANT   732    732  1     V -> I (in dbSNP:rs1801160 [NCBI]). VAR_014760 [3D]
VARIANT   886    886  1     R -> H (in allele DPYD*9B; 25% of activity; dbSNP:rs1801267 [NCBI]). VAR_005177 [3D]
VARIANT   995    995  1     V -> F (in allele DPYD*10; low activity; dbSNP:rs1801268 [NCBI]). VAR_005178 [3D]
CONFLICT   845    845        E -> G (in Ref. 4; BAF83906). 
CONFLICT   910    910        N -> S (in Ref. 1; AAA57474). 
CONFLICT   1024   1024        V -> G (in Ref. 6; AAI31779). 
Sequence information
Length: 1025 AA [This is the length of the unprocessed precursor] Molecular weight: 111401 Da [This is the MW of the unprocessed precursor] CRC64: 0201943955AB2C21 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAPVLSKDSA DIESILALNP RTQTHATLCS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD 

        70         80         90        100        110        120 
DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN 

       130        140        150        160        170        180 
PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPSLPPPE 

       190        200        210        220        230        240 
KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV 

       250        260        270        280        290        300 
VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD 

       310        320        330        340        350        360 
QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF 

       370        380        390        400        410        420 
IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN 

       430        440        450        460        470        480 
EDEDQMVHLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWG LPEVDPETMQ TSEAWVFAGG 

       490        500        510        520        530        540 
DVVGLANTTV ESVNDGKQAS WYIHKYVQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAGL 

       550        560        570        580        590        600 
KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY 

       610        620        630        640        650        660 
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS 

       670        680        690        700        710        720 
GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI 

       730        740        750        760        770        780 
ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS 

       790        800        810        820        830        840 
IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL 

       850        860        870        880        890        900 
KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ 

       910        920        930        940        950        960 
NVAFSPLKRN CFIPKRPIPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY 

       970        980        990       1000       1010       1020 
MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS 


VNPVC 

Q12882 in FASTA format

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