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Q28943

- DPYD_PIG

UniProt

Q28943 - DPYD_PIG

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Protein

Dihydropyrimidine dehydrogenase [NADP(+)]

Gene
DPYD
Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.3 Publications

Catalytic activityi

5,6-dihydrouracil + NADP+ = uracil + NADPH.2 Publications

Cofactori

Binds 4 4Fe-4S clusters. Contains approximately 16 iron atoms per subunit.4 Publications
FAD.4 Publications
FMN.4 Publications

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi79 – 791Iron-sulfur 1 (4Fe-4S)
Metal bindingi82 – 821Iron-sulfur 1 (4Fe-4S)
Metal bindingi87 – 871Iron-sulfur 1 (4Fe-4S)
Metal bindingi91 – 911Iron-sulfur 2 (4Fe-4S)
Binding sitei129 – 1291FAD; via carbonyl oxygen
Metal bindingi130 – 1301Iron-sulfur 2 (4Fe-4S)
Metal bindingi136 – 1361Iron-sulfur 2 (4Fe-4S)
Metal bindingi140 – 1401Iron-sulfur 1 (4Fe-4S)
Metal bindingi156 – 1561Iron-sulfur 2 (4Fe-4S)
Binding sitei235 – 2351FAD
Binding sitei261 – 2611FAD; via amide nitrogen and carbonyl oxygen
Binding sitei371 – 3711NADP
Binding sitei550 – 5501FMN
Binding sitei609 – 6091Substrate
Active sitei671 – 6711Proton acceptor1 Publication
Binding sitei709 – 7091FMN
Binding sitei767 – 7671FMN; via amide nitrogen
Metal bindingi953 – 9531Iron-sulfur 3 (4Fe-4S)
Metal bindingi956 – 9561Iron-sulfur 3 (4Fe-4S)
Metal bindingi959 – 9591Iron-sulfur 3 (4Fe-4S)
Metal bindingi963 – 9631Iron-sulfur 3 (4Fe-4S)
Metal bindingi986 – 9861Iron-sulfur 4 (4Fe-4S)
Metal bindingi989 – 9891Iron-sulfur 4 (4Fe-4S)
Metal bindingi992 – 9921Iron-sulfur 4 (4Fe-4S)
Metal bindingi996 – 9961Iron-sulfur 4 (4Fe-4S)

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi194 – 1985FAD
Nucleotide bindingi218 – 2269FAD
Nucleotide bindingi340 – 3434NADP
Nucleotide bindingi364 – 3652NADP
Nucleotide bindingi437 – 4393NADP
Nucleotide bindingi480 – 48910FAD
Nucleotide bindingi481 – 4877NADP
Nucleotide bindingi574 – 5752FMN
Nucleotide bindingi793 – 7953FMN
Nucleotide bindingi816 – 8172FMN

GO - Molecular functioni

  1. 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  2. dihydroorotate oxidase activity Source: InterPro
  3. dihydropyrimidine dehydrogenase (NADP+) activity Source: UniProtKB
  4. flavin adenine dinucleotide binding Source: UniProtKB
  5. FMN binding Source: UniProtKB
  6. metal ion binding Source: UniProtKB-KW
  7. NADP binding Source: UniProtKB
  8. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. beta-alanine biosynthetic process Source: UniProtKB-UniPathway
  2. thymidine catabolic process Source: UniProtKB
  3. UMP biosynthetic process Source: InterPro
  4. uracil catabolic process Source: UniProtKB
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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Unplaced

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi126 – 1261C → A: No effect on enzyme activity. Reduced iron content. 1 Publication
Mutagenesisi156 – 1561Q → E: Loss of enzyme activity. Reduces iron content. 1 Publication
Mutagenesisi235 – 2351R → A or K: Loss of enzyme activity. Loss of FAD binding. 1 Publication
Mutagenesisi670 – 6701S → A: Strongly reduced affinity for uracil. Reduces enzyme activity by 30%. 1 Publication
Mutagenesisi671 – 6711C → A: Reduces catalytic activity by 99%. 1 Publication
Mutagenesisi673 – 6731H → Q: Reduces activity by 50%.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 33PRO_0000021116
Chaini4 – 10251022Dihydropyrimidine dehydrogenase [NADP(+)]PRO_0000021117Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei384 – 3841N6-acetyllysine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ28943.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000007333.

Structurei

Secondary structure

1
1025
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 156
Turni16 – 183
Beta strandi24 – 263
Helixi31 – 4111
Helixi69 – 7810
Helixi86 – 894
Helixi97 – 1059
Helixi109 – 11911
Helixi123 – 1297
Helixi132 – 1343
Helixi136 – 1394
Helixi141 – 1444
Helixi152 – 16615
Helixi179 – 1813
Helixi184 – 1874
Beta strandi190 – 1934
Helixi197 – 20812
Beta strandi214 – 2229
Helixi226 – 2294
Turni233 – 2353
Helixi238 – 24912
Turni250 – 2523
Beta strandi254 – 2585
Helixi268 – 2736
Beta strandi278 – 2814
Helixi292 – 2943
Turni299 – 3024
Beta strandi303 – 3053
Helixi306 – 31712
Beta strandi322 – 3243
Beta strandi333 – 3386
Helixi342 – 35312
Beta strandi357 – 3626
Helixi367 – 3693
Helixi374 – 3829
Beta strandi386 – 3883
Beta strandi390 – 39910
Beta strandi402 – 41312
Beta strandi419 – 43012
Beta strandi432 – 4365
Helixi445 – 4506
Turni451 – 4533
Beta strandi460 – 4623
Turni466 – 4683
Beta strandi476 – 4783
Helixi481 – 4833
Helixi489 – 51022
Helixi527 – 5304
Beta strandi535 – 5373
Beta strandi540 – 5489
Helixi552 – 5543
Helixi557 – 56610
Beta strandi569 – 5724
Helixi579 – 5813
Beta strandi590 – 5923
Beta strandi607 – 6093
Helixi618 – 63114
Beta strandi635 – 6417
Helixi647 – 65913
Beta strandi663 – 6686
Beta strandi678 – 6803
Helixi684 – 6863
Helixi688 – 70114
Beta strandi706 – 7105
Helixi717 – 72711
Beta strandi730 – 7345
Beta strandi738 – 7403
Beta strandi750 – 7523
Turni755 – 7584
Beta strandi763 – 7675
Helixi768 – 7703
Helixi771 – 78414
Beta strandi790 – 7956
Helixi799 – 8079
Beta strandi811 – 8166
Helixi817 – 8204
Helixi826 – 84015
Helixi844 – 8463
Beta strandi848 – 8503
Beta strandi858 – 8603
Turni869 – 8735
Helixi880 – 89920
Helixi921 – 9244
Turni925 – 9284
Helixi929 – 9313
Helixi935 – 9373
Beta strandi940 – 9423
Beta strandi944 – 9485
Turni950 – 9523
Helixi958 – 9669
Beta strandi971 – 9733
Turni975 – 9773
Beta strandi980 – 9823
Helixi991 – 9955
Turni999 – 10013
Beta strandi1002 – 10065

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GT8X-ray3.30A/B/C/D1-1025[»]
1GTEX-ray1.65A/B/C/D1-1025[»]
1GTHX-ray2.25A/B/C/D1-1025[»]
1H7WX-ray1.90A/B/C/D1-1025[»]
1H7XX-ray2.01A/B/C/D1-1025[»]
ProteinModelPortaliQ28943.
SMRiQ28943. Positions 2-1020.

Miscellaneous databases

EvolutionaryTraceiQ28943.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini69 – 100324Fe-4S ferredoxin-type 1Add
BLAST
Domaini944 – 976334Fe-4S ferredoxin-type 2Add
BLAST
Domaini978 – 1007304Fe-4S ferredoxin-type 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni668 – 6703Substrate binding
Regioni736 – 7372Substrate binding

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0167.
HOGENOMiHOG000007797.
HOVERGENiHBG004351.
KOiK00207.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR017896. 4Fe4S_Fe-S-bd.
IPR017900. 4Fe4S_Fe_S_CS.
IPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR012135. Dihydroorotate_DH_1_2.
IPR028261. DPD_II.
IPR009051. Helical_ferredxn.
[Graphical view]
PfamiPF01180. DHO_dh. 1 hit.
PF14691. Fer4_20. 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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q28943-1 [UniParc]FASTAAdd to Basket

« Hide

MAPVLSKDVA DIESILALNP RTQSHAALHS TLAKKLDKKH WKRNPDKNCF     50
HCEKLENNFG DIKHTTLGER GALREAMRCL KCADAPCQKS CPTHLDIKSF 100
ITSISNKNYY GAAKMIFSDN PLGLTCGMVC PTSDLCVGGC NLYATEEGSI 150
NIGGLQQFAS EVFKAMNIPQ IRNPCLPSQE KMPEAYSAKI ALLGAGPASI 200
SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV VNFEIELMKD 250
LGVKIICGKS LSENEITLNT LKEEGYKAAF IGIGLPEPKT DDIFQGLTQD 300
QGFYTSKDFL PLVAKSSKAG MCACHSPLPS IRGAVIVLGA GDTAFDCATS 350
ALRCGARRVF LVFRKGFVNI RAVPEEVELA KEEKCEFLPF LSPRKVIVKG 400
GRIVAVQFVR TEQDETGKWN EDEDQIVHLK ADVVISAFGS VLRDPKVKEA 450
LSPIKFNRWD LPEVDPETMQ TSEPWVFAGG DIVGMANTTV ESVNDGKQAS 500
WYIHKYIQAQ YGASVSAKPE LPLFYTPVDL VDISVEMAGL KFINPFGLAS 550
AAPTTSSSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI VRGTTSGPMY 600
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW 650
MELSRKAEAS GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ 700
AVQIPFFAKL TPNVTDIVSI ARAAKEGGAD GVTATNTVSG LMGLKADGTP 750
WPAVGAGKRT TYGGVSGTAI RPIALRAVTT IARALPGFPI LATGGIDSAE 800
SGLQFLHSGA SVLQVCSAVQ NQDFTVIQDY CTGLKALLYL KSIEELQGWD 850
GQSPGTESHQ KGKPVPRIAE LMGKKLPNFG PYLEQRKKII AEEKMRLKEQ 900
NAAFPPLERK PFIPKKPIPA IKDVIGKALQ YLGTFGELSN IEQVVAVIDE 950
EMCINCGKCY MTCNDSGYQA IQFDPETHLP TVTDTCTGCT LCLSVCPIID 1000
CIRMVSRTTP YEPKRGLPLA VNPVC 1025
Length:1,025
Mass (Da):111,424
Last modified:November 1, 1997 - v1
Checksum:iB8D553AD862845D0
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U09179 mRNA. Translation: AAA57475.1.
PIRiB54718.
RefSeqiNP_999209.1. NM_214044.2.
UniGeneiSsc.153.

Genome annotation databases

GeneIDi397109.
KEGGissc:397109.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U09179 mRNA. Translation: AAA57475.1 .
PIRi B54718.
RefSeqi NP_999209.1. NM_214044.2.
UniGenei Ssc.153.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1GT8 X-ray 3.30 A/B/C/D 1-1025 [» ]
1GTE X-ray 1.65 A/B/C/D 1-1025 [» ]
1GTH X-ray 2.25 A/B/C/D 1-1025 [» ]
1H7W X-ray 1.90 A/B/C/D 1-1025 [» ]
1H7X X-ray 2.01 A/B/C/D 1-1025 [» ]
ProteinModelPortali Q28943.
SMRi Q28943. Positions 2-1020.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9823.ENSSSCP00000007333.

Chemistry

DrugBanki DB00544. Fluorouracil.

Proteomic databases

PaxDbi Q28943.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 397109.
KEGGi ssc:397109.

Organism-specific databases

CTDi 1806.

Phylogenomic databases

eggNOGi COG0167.
HOGENOMi HOG000007797.
HOVERGENi HBG004351.
KOi K00207.

Enzyme and pathway databases

UniPathwayi UPA00131 .

Miscellaneous databases

EvolutionaryTracei Q28943.

Family and domain databases

Gene3Di 3.20.20.70. 1 hit.
InterProi IPR017896. 4Fe4S_Fe-S-bd.
IPR017900. 4Fe4S_Fe_S_CS.
IPR013785. Aldolase_TIM.
IPR005720. Dihydroorotate_DH.
IPR012135. Dihydroorotate_DH_1_2.
IPR028261. DPD_II.
IPR009051. Helical_ferredxn.
[Graphical view ]
Pfami PF01180. DHO_dh. 1 hit.
PF14691. Fer4_20. 1 hit.
[Graphical view ]
SUPFAMi SSF46548. SSF46548. 1 hit.
TIGRFAMsi TIGR01037. pyrD_sub1_fam. 1 hit.
PROSITEi PS00198. 4FE4S_FER_1. 1 hit.
PS51379. 4FE4S_FER_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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], PARTIAL PROTEIN SEQUENCE.
    Tissue: Liver.
  2. "Porcine recombinant dihydropyrimidine dehydrogenase: comparison of the spectroscopic and catalytic properties of the wild-type and C671A mutant enzymes."
    Rosenbaum K., Jahnke K., Curti B., Hagen W.R., Schnackerz K.D., Vanoni M.A.
    Biochemistry 37:17598-17609(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MUTAGENESIS OF CYS-671.
  3. "Insights into the mechanism of dihydropyrimidine dehydrogenase from site-directed mutagenesis targeting the active site loop and redox cofactor coordination."
    Lohkamp B., Voevodskaya N., Lindqvist Y., Dobritzsch D.
    Biochim. Biophys. Acta 1804:2198-2206(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF CYS-126; GLN-156; ARG-235 AND SER-670.
  4. "Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil."
    Dobritzsch D., Schneider G., Schnackerz K.D., Lindqvist Y.
    EMBO J. 20:650-660(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEXES WITH 5-FLUOROURACIL; FAD; FMN; 4FE-4S IRON-SULFUR CLUSTER AND NADP, FUNCTION, SUBUNIT, COFACTOR.
  5. "Crystal structure of the productive ternary complex of dihydropyrimidine dehydrogenase with NADPH and 5-iodouracil. Implications for mechanism of inhibition and electron transfer."
    Dobritzsch D., Ricagno S., Schneider G., Schnackerz K.D., Lindqvist Y.
    J. Biol. Chem. 277:13155-13166(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH 5-IODOURACIL; FAD; FMN; 4FE-4S IRON-SULFUR CLUSTER AND NADP, COFACTOR, ACTIVE SITE.

Entry informationi

Entry nameiDPYD_PIG
AccessioniPrimary (citable) accession number: Q28943
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: December 11, 2013
This is version 113 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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