Reviewed, UniProtKB/Swiss-Prot O89000 (DPYD_RAT)

Names and origin

Protein names

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

Gene names

Name:	Dpyd
Synonyms:	DPD

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1025 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine By similarity.
Catalytic activity	5,6-dihydrouracil + NADP+ = uracil + NADPH.
Cofactor	Binds 2 4Fe-4S clusters By similarity. FAD By similarity. FMN By similarity.
Enzyme regulation	Inactivated by 5-iodouracil By similarity.
Pathway	Amino-acid biosynthesis; beta-alanine biosynthesis.
Subunit structure	Homodimer By similarity.
Subcellular location	Cytoplasm By similarity.
Sequence similarities	Belongs to the dihydropyrimidine dehydrogenase family. Contains 3 4Fe-4S ferredoxin-type domains.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Repeat
Ligand	4Fe-4S FAD FMN Flavoprotein Iron Iron-sulfur Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	'de novo' pyrimidine base biosynthetic process Inferred from electronic annotation. Source: InterPro UMP biosynthetic process Inferred from electronic annotation. Source: InterPro circadian rhythm Inferred from direct assay. Source: RGD oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to drug Inferred from direct assay. Source: RGD response to glucocorticoid stimulus Ref.1 Inferred from expression pattern. Source: RGD response to nutrient Inferred from direct assay. Source: RGD thymidine catabolic process Inferred from sequence or structural similarity. Source: UniProtKB uracil catabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB soluble fraction Inferred from direct assay. Source: RGD
Molecular function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NADP or NADPH binding Inferred from direct assay. Source: UniProtKB dihydroorotate oxidase activity Inferred from electronic annotation. Source: InterPro dihydropyrimidine dehydrogenase (NADP+) activity Ref.1 Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Inferred from direct assay. Source: UniProtKB uracil binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1025	1025	Dihydropyrimidine dehydrogenase [NADP+]		PRO_0000327502
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
Sites
	Metal binding	953	1	Iron-sulfur 1 (4Fe-4S) Potential
	Metal binding	956	1	Iron-sulfur 1 (4Fe-4S) Potential
	Metal binding	959	1	Iron-sulfur 1 (4Fe-4S) Potential
	Metal binding	963	1	Iron-sulfur 1 (4Fe-4S) Potential
	Metal binding	986	1	Iron-sulfur 2 (4Fe-4S) Potential
	Metal binding	989	1	Iron-sulfur 2 (4Fe-4S) Potential
	Metal binding	992	1	Iron-sulfur 2 (4Fe-4S) Potential
	Metal binding	996	1	Iron-sulfur 2 (4Fe-4S) Potential
Amino acid modifications
	Modified residue	384	1	N6-acetyllysine By similarity
	Modified residue	577	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O89000-1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 07859E73D249828C	FASTA	1,025	111,468
	10 20 30 40 50 60 MAGVLSRDAP DIESILALNP RIQAHATLRS TMAKKLDKKH WKRNTDKNCF ICEKLENNFD 70 80 90 100 110 120 DIKHTTLGER GALREAVRCL KCADAPCQKS CPTSLDIKSF ITSIANKNYY GAAKLIFSDN 130 140 150 160 170 180 PLGLTCGMVC PTSDLCVGGC NLHATEEGPI NIGGLQQFAT EVFKAMNIPQ IRSPLLPPPE 190 200 210 220 230 240 HMPEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV 250 260 270 280 290 300 VNFEIELMKD LGVKIICGKS ISTDEMTLST LKENGYKAAF IGIGLPEPKK DHIFQGLTQV 310 320 330 340 350 360 QGFYTSKDFL PLVAKGSKPG MCACHSPLPS VRGAVIVLGA GDTAFDCATS ALRCGARRVF 370 380 390 400 410 420 IVFRKGFANI RAVPEEMELA KEEKCEFLPF LSPRKVIVKD GKIVGMQFVR TEQDETGNWV 430 440 450 460 470 480 EDEEQIVRLK ADVVISPFGS VLDDPKVIEA LSPIKFNRWG LPEVNPETMQ TSEPWVFAGG 490 500 510 520 530 540 DVVGMANTTV ESVNDGKQAS WYIHEYIQAQ YGALVPSQPT LPLFYTPVDL VDISVEMAGL 550 560 570 580 590 600 RFPNPFGLAS ATPATSTPMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPLY 610 620 630 640 650 660 GPGQSSFLNI ELISEKTAAY WCHSVTELKA DFPDNILIAS IMCSYNKNDW MELSKMAEAS 670 680 690 700 710 720 GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ SVRVPFFAKL TPNVTDIVSI 730 740 750 760 770 780 ARAAKEGGAD GVTATNTVSG LMGLKADGSP WPSVGSGKRT TYGGVSGTTI RPIALRAVTA 790 800 810 820 830 840 IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL 850 860 870 880 890 900 KSIEELSDWD GQSPPTMSHQ KGKPVPHIAE LMGQKLPSFG PYLERRKKIL AASKIRENDQ 910 920 930 940 950 960 NRACSPLQRK HFNSQKPIPA IKDVIGKSLQ YLGTFGELNI MEQVVALIDE EMCINCGKCY 970 980 990 1000 1010 1020 MTCNDSGYQA IQFDPETHLP TVSDTCTGCT LCLSVCPIMD CIRMVSRATP YEPKRGLPLA VKPVC

References

[1]	"Cloning of rat dihydropyrimidine dehydrogenase and correlation of its mRNA increase in the rat liver with age." Kimura M., Fujimoto Sakata S., Matoba Y., Matsuda K., Kontani Y., Kaneko M., Tamaki N. J. Nutr. Sci. Vitaminol. 44:537-546(1998) [PubMed: 9819714] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D85035 mRNA. Translation: BAA33218.1.
IPI	IPI00209289.
RefSeq	NP_112289.1.
UniGene	Rn.158382
3D structure databases
HSSP	HSSP built from PDB template 1H7X based on UniProtKB Q28943.
SMR	O89000. Positions 2-1017.
ModBase	Search...
Protein-protein interaction databases
STRING	O89000.
Proteomic databases
PRIDE	O89000.
Genome annotation databases
Ensembl	ENSRNOT00000023229; ENSRNOP00000023227; ENSRNOG00000017105; Rattus norvegicus. [Genome view]
GeneID	81656.
KEGG	rno:81656.
Organism-specific databases
CTD	81656.
RGD	621218. Dpyd.
Phylogenomic databases
HOVERGEN	O89000.
Enzyme and pathway databases
BRENDA	1.3.1.2. 248.
Gene expression databases
Genevestigator	O89000.
Family and domain databases
InterPro	IPR017896. 4Fe4S_Fe-S-bd. IPR001450. 4Fe4S_Fe_S_bd_subgr. IPR017900. 4Fe4S_Fe_S_CS. IPR000759. Adrndx_reductase. IPR013785. Aldolase_TIM. IPR012135. Dihydroorotate_DH_1_2. IPR005720. Dihydroorotate_DH_1_core. IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR012285. Fum_reductase_C. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.20.20.70. Aldolase_TIM. 1 hit. G3DSA:1.10.1060.10. Fum_reductase_C. 1 hit. G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF01180. DHO_dh. 1 hit. PF00037. Fer4. 1 hit. PF07992. Pyr_redox_2. 1 hit. [Graphical view]
PRINTS	PR00419. ADXRDTASE.
ProDom	PD000139. FAD_pyr_redox. 1 hit. [Graphical view] [Entries sharing at least one domain]
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 Resources
NextBio	615210.

Entry information

Entry name

DPYD_RAT

Accession

Primary (citable) accession number: O89000

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	November 1, 1998
Last modified:	October 13, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)