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Protein

Dihydropyrimidine dehydrogenase [NADP(+)]

Gene

DPYD

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.

Catalytic activityi

5,6-dihydrouracil + NADP+ = uracil + NADPH.

Cofactori

Protein has several cofactor binding sites:
  • [4Fe-4S] clusterBy similarityNote: Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms per subunit.By similarity
  • FAD
  • FMN

Enzyme regulationi

Inactivated by 5-iodouracil.1 Publication

Pathwayi: beta-alanine biosynthesis

This protein is involved in the pathway beta-alanine biosynthesis, which is part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the pathway beta-alanine biosynthesis and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi79Iron-sulfur 1 (4Fe-4S)By similarity1
Metal bindingi82Iron-sulfur 1 (4Fe-4S)By similarity1
Metal bindingi87Iron-sulfur 1 (4Fe-4S)By similarity1
Metal bindingi91Iron-sulfur 2 (4Fe-4S)By similarity1
Binding sitei129FAD; via carbonyl oxygenBy similarity1
Metal bindingi130Iron-sulfur 2 (4Fe-4S)By similarity1
Metal bindingi136Iron-sulfur 2 (4Fe-4S)By similarity1
Metal bindingi140Iron-sulfur 1 (4Fe-4S)By similarity1
Metal bindingi156Iron-sulfur 2 (4Fe-4S)By similarity1
Binding sitei235FADBy similarity1
Binding sitei261FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei371NADPBy similarity1
Binding sitei550FMNBy similarity1
Binding sitei609SubstrateBy similarity1
Active sitei671Proton acceptorBy similarity1
Binding sitei709FMNBy similarity1
Binding sitei767FMN; via amide nitrogenBy similarity1
Metal bindingi953Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi956Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi959Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi963Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi986Iron-sulfur 4 (4Fe-4S)By similarity1
Metal bindingi989Iron-sulfur 4 (4Fe-4S)By similarity1
Metal bindingi992Iron-sulfur 4 (4Fe-4S)By similarity1
Metal bindingi996Iron-sulfur 4 (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi194 – 198FADBy similarity5
Nucleotide bindingi218 – 226FADBy similarity9
Nucleotide bindingi340 – 343NADPBy similarity4
Nucleotide bindingi364 – 365NADPBy similarity2
Nucleotide bindingi437 – 439NADPBy similarity3
Nucleotide bindingi480 – 489FADBy similarity10
Nucleotide bindingi481 – 487NADPBy similarity7
Nucleotide bindingi574 – 575FMNBy similarity2
Nucleotide bindingi793 – 795FMNBy similarity3
Nucleotide bindingi816 – 817FMNBy similarity2

GO - Molecular functioni

  • 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  • dihydropyrimidine dehydrogenase (NADP+) activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • NADP binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

4Fe-4S, FAD, Flavoprotein, FMN, Iron, Iron-sulfur, Metal-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00131.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropyrimidine dehydrogenase [NADP(+)] (EC:1.3.1.2)
Short name:
DHPDHase
Short name:
DPD
Alternative name(s):
Dihydrothymine dehydrogenase
Dihydrouracil dehydrogenase
Gene namesi
Name:DPYD
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000799961 – 1025Dihydropyrimidine dehydrogenase [NADP(+)]Add BLAST1025

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei384N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ28007.
PRIDEiQ28007.

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007139.

Structurei

3D structure databases

ProteinModelPortaliQ28007.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 1004Fe-4S ferredoxin-type 1PROSITE-ProRule annotationAdd BLAST32
Domaini944 – 9764Fe-4S ferredoxin-type 2PROSITE-ProRule annotationAdd BLAST33
Domaini978 – 10074Fe-4S ferredoxin-type 3PROSITE-ProRule annotationAdd BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni668 – 670Substrate bindingBy similarity3
Regioni736 – 737Substrate bindingBy similarity2

Sequence similaritiesi

Contains 3 4Fe-4S ferredoxin-type domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0399. Eukaryota.
COG0167. LUCA.
COG0493. LUCA.
COG1146. LUCA.
HOGENOMiHOG000007797.
HOVERGENiHBG004351.
InParanoidiQ28007.
KOiK00207.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
3.50.50.60. 3 hits.
InterProiIPR017896. 4Fe4S_Fe-S-bd.
IPR017900. 4Fe4S_Fe_S_CS.
IPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR028261. DPD_II.
IPR023753. FAD/NAD-binding_dom.
IPR009051. Helical_ferredxn.
[Graphical view]
PfamiPF01180. DHO_dh. 1 hit.
PF14691. Fer4_20. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
SUPFAMiSSF46548. SSF46548. 1 hit.
TIGRFAMsiTIGR01037. pyrD_sub1_fam. 1 hit.
PROSITEiPS00198. 4FE4S_FER_1. 1 hit.
PS51379. 4FE4S_FER_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q28007-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPVLSKDVA DIESILALNP RTQSRATLRS TLAKKLDKKH WKRNPDKNCF
60 70 80 90 100
NCEKLENNFD DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF
110 120 130 140 150
ITSISNKNYY GAAKMIFSDN PLGLTCGMVC PTSDLCVGGC NLYATEEGPI
160 170 180 190 200
NIGGLQQYAT EVFKAMNIPQ IRNPSLPPPE KMPEAYSAKI ALLGAGPASI
210 220 230 240 250
SCASFLARLG YNDITIFEKQ EYVGGISTSE IPQFRLPYDV VNFEIELMKD
260 270 280 290 300
LGVKIICGKS LSVNDITLST LKEEGYKAAF IGIGLPEPKK DHIFQGLTQD
310 320 330 340 350
QGFYTSKDFL PLVAKSSKAG MCACHSPLLS IRGTVIVLGA GDTAFDCATS
360 370 380 390 400
ALRCGARRVF IVFRKGFVNI RAVPEEVELA REEKCEFLPF LSPRKVIVKG
410 420 430 440 450
GRIVAMQFVR TEQDETGKWN EDGDQIACLK ADVVISAFGS VLSDPKVKEA
460 470 480 490 500
LSPIKFNRWD LPEVDPETMQ TSEPWVFAGG DVVGIANTTV EAVNDGKQAS
510 520 530 540 550
WYIHRYIQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAAL KFTNPFGLAS
560 570 580 590 600
ATPTTSSSMI RRAFEAGWAF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY
610 620 630 640 650
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNRNDW
660 670 680 690 700
MELSRKAEAS GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ
710 720 730 740 750
AVRIPFFAKL TPNVTDIVSI ARAAKEGGAN GVTATNTVSG LMGLKADGTP
760 770 780 790 800
WPAVGREKRT TYGGVSGTAI RPIALRAVTT IARALPEFPI LATGGIDSAE
810 820 830 840 850
SGLQFLHGGA SVLQVCSAIQ NQDFTIIQDY CTGLKALLYL KSIEELQDWD
860 870 880 890 900
GQSPATKSHQ KGKPVPCIAE LVGKKLPSFG PYLEKCKKII AEEKLRLKKE
910 920 930 940 950
NVTVLPLERN HFIPKKPIPS VKDVIGKALQ YLGTYGELNN TEQVVAVIDE
960 970 980 990 1000
EMCINCGKCY MTCNDSGYQA IQFDPETHLP TVTDTCTGCT LCLSVCPIID
1010 1020
CIKMVSRTTP YEPKRGLPLA VNPVS
Length:1,025
Mass (Da):111,697
Last modified:November 1, 1997 - v1
Checksum:i5B55F93A06C47F4F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20981 mRNA. Translation: AAB40985.1.
PIRiA44626.
RefSeqiNP_776466.1. NM_174041.2.
UniGeneiBt.2424.

Genome annotation databases

GeneIDi281124.
KEGGibta:281124.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20981 mRNA. Translation: AAB40985.1.
PIRiA44626.
RefSeqiNP_776466.1. NM_174041.2.
UniGeneiBt.2424.

3D structure databases

ProteinModelPortaliQ28007.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000007139.

Proteomic databases

PaxDbiQ28007.
PRIDEiQ28007.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281124.
KEGGibta:281124.

Organism-specific databases

CTDi1806.

Phylogenomic databases

eggNOGiKOG0399. Eukaryota.
COG0167. LUCA.
COG0493. LUCA.
COG1146. LUCA.
HOGENOMiHOG000007797.
HOVERGENiHBG004351.
InParanoidiQ28007.
KOiK00207.

Enzyme and pathway databases

UniPathwayiUPA00131.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
3.50.50.60. 3 hits.
InterProiIPR017896. 4Fe4S_Fe-S-bd.
IPR017900. 4Fe4S_Fe_S_CS.
IPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR028261. DPD_II.
IPR023753. FAD/NAD-binding_dom.
IPR009051. Helical_ferredxn.
[Graphical view]
PfamiPF01180. DHO_dh. 1 hit.
PF14691. Fer4_20. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]
SUPFAMiSSF46548. SSF46548. 1 hit.
TIGRFAMsiTIGR01037. pyrD_sub1_fam. 1 hit.
PROSITEiPS00198. 4FE4S_FER_1. 1 hit.
PS51379. 4FE4S_FER_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPYD_BOVIN
AccessioniPrimary (citable) accession number: Q28007
Secondary accession number(s): Q9TRV4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 5, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.