Q12882 (DPYD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dihydropyrimidine dehydrogenase [NADP(+)]
Short name=DHPDHase
Short name=DPD
EC=1.3.1.2

Alternative name(s):
Dihydrothymine dehydrogenase
Dihydrouracil dehydrogenase

Gene names

Name:

DPYD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1025 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Catalytic activity	5,6-dihydrouracil + NADP+ = uracil + NADPH.
Cofactor	Binds 2 FAD. Binds 2 FMN. Binds 4 4Fe-4S clusters. Contains approximately 16 iron atoms per subunit By similarity.
Pathway	Amino-acid biosynthesis; beta-alanine biosynthesis.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Tissue specificity	Found in most tissues with greatest activity found in liver and peripheral blood mononuclear cells.
Involvement in disease	Dihydropyrimidine dehydrogenase deficiency (DPYDD) [MIM:274270]: A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6 Ref.13 Ref.14
Sequence similarities	Belongs to the dihydropyrimidine dehydrogenase family. Contains 3 4Fe-4S ferredoxin-type domains.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat
Ligand	4Fe-4S FAD FMN Flavoprotein Iron Iron-sulfur Metal-binding NADP Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	UMP biosynthetic process Inferred from electronic annotation. Source: InterPro beta-alanine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway purine nucleobase catabolic process Inferred from mutant phenotype PubMed 11988088. Source: UniProtKB thymidine catabolic process Inferred from direct assay Ref.11. Source: UniProtKB thymine catabolic process Inferred from direct assay PubMed 10410956. Source: UniProtKB uracil catabolic process Inferred from direct assay Ref.11PubMed 18075467. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 9348115. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NADP binding Inferred from sequence or structural similarity. Source: UniProtKB dihydroorotate oxidase activity Inferred from electronic annotation. Source: InterPro dihydropyrimidine dehydrogenase (NADP+) activity Inferred from direct assay PubMed 10410956Ref.11PubMed 18075467. Source: UniProtKB flavin adenine dinucleotide binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q12882-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q12882-2)

The sequence of this isoform differs from the canonical sequence as follows:
     162-173: VFKAMSIPQIRN → TLILAFSLMNHL
     174-1025: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 3	3			PRO_0000021114
	Chain	4 – 1025	1022	Dihydropyrimidine dehydrogenase [NADP(+)]		PRO_0000021115
Regions
	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
	Nucleotide binding	194 – 198	5	FAD By similarity
	Nucleotide binding	218 – 226	9	FAD By similarity
	Nucleotide binding	340 – 343	4	NADP By similarity
	Nucleotide binding	364 – 365	2	NADP By similarity
	Nucleotide binding	437 – 439	3	NADP By similarity
	Nucleotide binding	480 – 489	10	FAD By similarity
	Nucleotide binding	481 – 487	7	NADP By similarity
	Nucleotide binding	574 – 575	2	FMN By similarity
	Nucleotide binding	793 – 795	3	FMN By similarity
	Nucleotide binding	816 – 817	2	FMN By similarity
	Region	668 – 670	3	Substrate binding By similarity
	Region	736 – 737	2	Substrate binding By similarity
Sites
	Active site	671	1	Proton acceptor By similarity
	Metal binding	79	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	82	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	87	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	91	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	130	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	136	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	140	1	Iron-sulfur 1 (4Fe-4S) By similarity
	Metal binding	156	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	953	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	956	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	959	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	963	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	986	1	Iron-sulfur 4 (4Fe-4S) By similarity
	Metal binding	989	1	Iron-sulfur 4 (4Fe-4S) By similarity
	Metal binding	992	1	Iron-sulfur 4 (4Fe-4S) By similarity
	Metal binding	996	1	Iron-sulfur 4 (4Fe-4S) By similarity
	Binding site	129	1	FAD; via carbonyl oxygen By similarity
	Binding site	235	1	FAD By similarity
	Binding site	261	1	FAD; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	371	1	NADP By similarity
	Binding site	550	1	FMN By similarity
	Binding site	609	1	Substrate By similarity
	Binding site	709	1	FMN By similarity
	Binding site	767	1	FMN; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	384	1	N6-acetyllysine Ref.12
Natural variations
	Alternative sequence	162 – 173	12	VFKAM…PQIRN → TLILAFSLMNHL in isoform 2.		VSP_044929
	Alternative sequence	174 – 1025	852	Missing in isoform 2.		VSP_044930
	Natural variant	29	1	C → R in DPYDD; allele DPYD*9A and allele DPYD*9B; loss of activity. Ref.5 Ref.6 Ref.13 Ref.14 Ref.15 Corresponds to variant rs1801265 [ dbSNP | Ensembl ].		VAR_005173
	Natural variant	166	1	M → V. Corresponds to variant rs2297595 [ dbSNP | Ensembl ].		VAR_054034
	Natural variant	235	1	R → W in DPYDD; allele DPYD*8; loss of activity. Ref.13 Ref.14 Corresponds to variant rs1801266 [ dbSNP | Ensembl ].		VAR_005174
	Natural variant	534	1	S → N in allele DPYD*4; low activity. Corresponds to variant rs1801158 [ dbSNP | Ensembl ].		VAR_005175
	Natural variant	543	1	I → V in allele DPYD*5. Ref.8 Corresponds to variant rs1801159 [ dbSNP | Ensembl ].		VAR_005176
	Natural variant	732	1	V → I. Ref.8 Corresponds to variant rs1801160 [ dbSNP | Ensembl ].		VAR_014760
	Natural variant	886	1	R → H in DPYDD; allele DPYD*9B; 25% of activity. Ref.13 Ref.14 Corresponds to variant rs1801267 [ dbSNP | Ensembl ].		VAR_005177
	Natural variant	995	1	V → F in allele DPYD*10; low activity. Corresponds to variant rs1801268 [ dbSNP | Ensembl ].		VAR_005178
Experimental info
	Sequence conflict	131	1	P → S in AAI08743. Ref.6
	Sequence conflict	845	1	E → G in BAF83906. Ref.5
	Sequence conflict	910	1	N → S in AAA57474. Ref.1
	Sequence conflict	1024	1	V → G in AAI31779. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 13, 2007. Version 2. Checksum: 0201943955AB2C21	FASTA	1,025	111,401
	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
	Isoform 2 [UniParc]. Checksum: 94D241E912F29B6B	FASTA	173	18,936
	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 PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT ETLILAFSLM NHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria." Yokota H., Fernandez-Salguero P., Furuya H., Lin K., McBride O.W., Podschun B., Schnackerz K.D., Gonzalez F.J. J. Biol. Chem. 269:23192-23196(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Structural organization of the human dihydropyrimidine dehydrogenase gene." Johnson M.R., Wang K., Tillmanns S., Albin N., Diasio R.B. Cancer Res. 57:1660-1663(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine." Ogura K., Nishiyama T., Takubo H., Kato A., Okuda H., Arakawa K., Fukushima M., Nagayama S., Kawaguchi Y., Watabe T. Cancer Lett. 122:107-113(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT DPYDD ARG-29.
[6]	"The DNA sequence and biological annotation of human chromosome 1." 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. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT DPYDD ARG-29.
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS VAL-543 AND ILE-732. Tissue: Skin and Uterus.
[9]	"A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency." Vreken P., van Kuilenburg A.B.P., Meinsma R., Smit G.P.A., Bakker H.D., de Abreu R.A., van Gennip A.H. J. Inherit. Metab. Dis. 19:645-654(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635. Tissue: Liver.
[10]	"Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin." Fernandez-Salguero P.M., Sapone A., Wei X., Holt J.R., Jones S., Idle J.R., Gonzalez F.J. Pharmacogenetics 7:161-163(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635.
[11]	"Purification and characterization of dihydropyrimidine dehydrogenase from human liver." Lu Z.-H., Zhang R., Diasio R.B. J. Biol. Chem. 267:17102-17109(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-384, MASS SPECTROMETRY.
[13]	"Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W." Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H. Hum. Genet. 101:333-338(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DPYDD ARG-29; TRP-235 AND HIS-886.
[14]	"Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene." Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H. J. Inherit. Metab. Dis. 20:335-338(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DPYDD ARG-29; TRP-235 AND HIS-886.
[15]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-29.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U09178 mRNA. Translation: AAA57474.1. U20938 mRNA. Translation: AAB51366.1. AB003063 mRNA. Translation: BAA89789.1. BT006740 mRNA. Translation: AAP35386.1. AK291217 mRNA. Translation: BAF83906.1. AL356457 , AC091608, AC093576, AC099787, AC114878, AC138135, BX908805 Genomic DNA. Translation: CAH70570.1. BX908805 , AC091608, AC093576, AC099787, AC114878, AC138135, AL356457 Genomic DNA. Translation: CAI15125.1. CH471097 Genomic DNA. Translation: EAW73002.1. BC008379 mRNA. Translation: AAH08379.1. BC064027 mRNA. Translation: AAH64027.1. BC108742 mRNA. Translation: AAI08743.1. BC131777 mRNA. Translation: AAI31778.1. BC131778 mRNA. Translation: AAI31779.1. X95670 Genomic DNA. Translation: CAA64973.1. U57655 Genomic DNA. Translation: AAB07049.1.
IPI	IPI00029772. IPI00095889.
PIR	A54718.
RefSeq	NP_000101.2. NM_000110.3. NP_001153773.1. NM_001160301.1.
UniGene	Hs.335034.
3D structure databases
ProteinModelPortal	Q12882.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12882. 18 interactions.
STRING	9606.ENSP00000359211.
PTM databases
PhosphoSite	Q12882.
Polymorphism databases
DMDM	160332325.
Proteomic databases
PaxDb	Q12882.
PRIDE	Q12882.
Protocols and materials databases
DNASU	1806.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370192; ENSP00000359211; ENSG00000188641.
GeneID	1806.
KEGG	hsa:1806.
UCSC	uc001drv.3. human. uc001drw.3. human.
Organism-specific databases
CTD	1806.
GeneCards	GC01M097543.
H-InvDB	HIX0000804.
HGNC	HGNC:3012. DPYD.
HPA	CAB033241.
MIM	274270. phenotype. 612779. gene.
neXtProt	NX_Q12882.
Orphanet	240839. 5-fluorouracil toxicity. 240855. Capecitabine toxicity. 1675. Dihydropyrimidine dehydrogenase deficiency. 240955. Susceptibility to adverse reaction due to 5-fluorouracil treatment. 240963. Susceptibility to adverse reaction due to capecitabine treatment.
PharmGKB	PA145.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0167.
HOVERGEN	HBG004351.
InParanoid	Q12882.
KO	K00207.
OrthoDB	EOG44J2H8.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00131.
Gene expression databases
ArrayExpress	Q12882.
Bgee	Q12882.
CleanEx	HS_DPYD.
Genevestigator	Q12882.
GermOnline	ENSG00000188641. Homo sapiens.
Family and domain databases
Gene3D	1.10.1060.10. 1 hit. 3.20.20.70. 1 hit.
InterPro	IPR017896. 4Fe4S_Fe-S-bd. IPR017900. 4Fe4S_Fe_S_CS. IPR013785. Aldolase_TIM. IPR005720. Dihydroorotate_DH. IPR012135. Dihydroorotate_DH_1_2. IPR012285. Fum_reductase_C. IPR009051. Helical_ferredxn. [Graphical view]
Pfam	PF01180. DHO_dh. 1 hit. [Graphical view]
SUPFAM	SSF46548. Helical_ferredxn. 1 hit.
TIGRFAMs	TIGR01037. pyrD_sub1_fam. 1 hit.
PROSITE	PS00198. 4FE4S_FER_1. 1 hit. PS51379. 4FE4S_FER_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q12882.
ChEMBL	CHEMBL3172.
ChiTaRS	DPYD. human.
DrugBank	DB01101. Capecitabine. DB00109. Enfuvirtide.
GenomeRNAi	1806.
NextBio	35501869.
SOURCE	Search...

Entry information

Entry name

DPYD_HUMAN

Accession

Primary (citable) accession number: Q12882
Secondary accession number(s): A2RRQ2 , A2RRQ3, A8K5A2, A8MWG9, B1AN21, E9PFN1, Q16694, Q16761, Q32NB0, Q96HL6, Q96TH1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 13, 2007
Last modified:	May 29, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.