Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q28943

- DPYD_PIG

UniProt

Q28943 - DPYD_PIG

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

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

Protein has several cofactor binding sites:

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 oxygen1 Publication
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 – 2351FAD1 Publication
Binding sitei261 – 2611FAD; via amide nitrogen and carbonyl oxygen1 Publication
Binding sitei371 – 3711NADP1 Publication
Binding sitei550 – 5501FMN1 Publication
Binding sitei609 – 6091Substrate
Active sitei671 – 6711Proton acceptor1 Publication
Binding sitei709 – 7091FMN1 Publication
Binding sitei767 – 7671FMN; via amide nitrogen1 Publication
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 – 1985FAD1 Publication
Nucleotide bindingi218 – 2269FAD1 Publication
Nucleotide bindingi340 – 3434NADP1 Publication
Nucleotide bindingi364 – 3652NADP1 Publication
Nucleotide bindingi437 – 4393NADP1 Publication
Nucleotide bindingi480 – 48910FAD1 Publication
Nucleotide bindingi481 – 4877NADP1 Publication
Nucleotide bindingi574 – 5752FMN1 Publication
Nucleotide bindingi793 – 7953FMN1 Publication
Nucleotide bindingi816 – 8172FMN1 Publication

GO - Molecular functioni

  1. 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  2. dihydroorotate dehydrogenase 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-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ28943.

Interactioni

Subunit structurei

Homodimer.3 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 – 156Combined sources
Turni16 – 183Combined sources
Beta strandi24 – 263Combined sources
Helixi31 – 4111Combined sources
Helixi69 – 7810Combined sources
Helixi86 – 894Combined sources
Helixi97 – 1059Combined sources
Helixi109 – 11911Combined sources
Helixi123 – 1297Combined sources
Helixi132 – 1343Combined sources
Helixi136 – 1394Combined sources
Helixi141 – 1444Combined sources
Helixi152 – 16615Combined sources
Helixi179 – 1813Combined sources
Helixi184 – 1874Combined sources
Beta strandi190 – 1934Combined sources
Helixi197 – 20812Combined sources
Beta strandi214 – 2229Combined sources
Helixi226 – 2294Combined sources
Turni233 – 2353Combined sources
Helixi238 – 24912Combined sources
Turni250 – 2523Combined sources
Beta strandi254 – 2585Combined sources
Helixi268 – 2736Combined sources
Beta strandi278 – 2814Combined sources
Helixi292 – 2943Combined sources
Turni299 – 3024Combined sources
Beta strandi303 – 3053Combined sources
Helixi306 – 31712Combined sources
Beta strandi322 – 3243Combined sources
Beta strandi333 – 3386Combined sources
Helixi342 – 35312Combined sources
Beta strandi357 – 3626Combined sources
Helixi367 – 3693Combined sources
Helixi374 – 3829Combined sources
Beta strandi386 – 3883Combined sources
Beta strandi390 – 39910Combined sources
Beta strandi402 – 41312Combined sources
Beta strandi419 – 43012Combined sources
Beta strandi432 – 4365Combined sources
Helixi445 – 4506Combined sources
Turni451 – 4533Combined sources
Beta strandi460 – 4623Combined sources
Turni466 – 4683Combined sources
Beta strandi476 – 4783Combined sources
Helixi481 – 4833Combined sources
Helixi489 – 51022Combined sources
Helixi527 – 5304Combined sources
Beta strandi535 – 5373Combined sources
Beta strandi540 – 5489Combined sources
Helixi552 – 5543Combined sources
Helixi557 – 56610Combined sources
Beta strandi569 – 5724Combined sources
Helixi579 – 5813Combined sources
Beta strandi590 – 5923Combined sources
Beta strandi607 – 6093Combined sources
Helixi618 – 63114Combined sources
Beta strandi635 – 6417Combined sources
Helixi647 – 65913Combined sources
Beta strandi663 – 6686Combined sources
Beta strandi678 – 6803Combined sources
Helixi684 – 6863Combined sources
Helixi688 – 70114Combined sources
Beta strandi706 – 7105Combined sources
Helixi717 – 72711Combined sources
Beta strandi730 – 7345Combined sources
Beta strandi738 – 7403Combined sources
Beta strandi750 – 7523Combined sources
Turni755 – 7584Combined sources
Beta strandi763 – 7675Combined sources
Helixi768 – 7703Combined sources
Helixi771 – 78414Combined sources
Beta strandi790 – 7956Combined sources
Helixi799 – 8079Combined sources
Beta strandi811 – 8166Combined sources
Helixi817 – 8204Combined sources
Helixi826 – 84015Combined sources
Helixi844 – 8463Combined sources
Beta strandi848 – 8503Combined sources
Beta strandi858 – 8603Combined sources
Turni869 – 8735Combined sources
Helixi880 – 89920Combined sources
Helixi921 – 9244Combined sources
Turni925 – 9284Combined sources
Helixi929 – 9313Combined sources
Helixi935 – 9373Combined sources
Beta strandi940 – 9423Combined sources
Beta strandi944 – 9485Combined sources
Turni950 – 9523Combined sources
Helixi958 – 9669Combined sources
Beta strandi971 – 9733Combined sources
Turni975 – 9773Combined sources
Beta strandi980 – 9823Combined sources
Helixi991 – 9955Combined sources
Turni999 – 10013Combined sources
Beta strandi1002 – 10065Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ28943.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG0167.
HOGENOMiHOG000007797.
HOVERGENiHBG004351.
InParanoidiQ28943.
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

        10         20         30         40         50
MAPVLSKDVA DIESILALNP RTQSHAALHS TLAKKLDKKH WKRNPDKNCF
60 70 80 90 100
HCEKLENNFG DIKHTTLGER GALREAMRCL KCADAPCQKS CPTHLDIKSF
110 120 130 140 150
ITSISNKNYY GAAKMIFSDN PLGLTCGMVC PTSDLCVGGC NLYATEEGSI
160 170 180 190 200
NIGGLQQFAS EVFKAMNIPQ IRNPCLPSQE KMPEAYSAKI ALLGAGPASI
210 220 230 240 250
SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV VNFEIELMKD
260 270 280 290 300
LGVKIICGKS LSENEITLNT LKEEGYKAAF IGIGLPEPKT DDIFQGLTQD
310 320 330 340 350
QGFYTSKDFL PLVAKSSKAG MCACHSPLPS IRGAVIVLGA GDTAFDCATS
360 370 380 390 400
ALRCGARRVF LVFRKGFVNI RAVPEEVELA KEEKCEFLPF LSPRKVIVKG
410 420 430 440 450
GRIVAVQFVR TEQDETGKWN EDEDQIVHLK ADVVISAFGS VLRDPKVKEA
460 470 480 490 500
LSPIKFNRWD LPEVDPETMQ TSEPWVFAGG DIVGMANTTV ESVNDGKQAS
510 520 530 540 550
WYIHKYIQAQ YGASVSAKPE LPLFYTPVDL VDISVEMAGL KFINPFGLAS
560 570 580 590 600
AAPTTSSSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI VRGTTSGPMY
610 620 630 640 650
GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW
660 670 680 690 700
MELSRKAEAS GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ
710 720 730 740 750
AVQIPFFAKL TPNVTDIVSI ARAAKEGGAD GVTATNTVSG LMGLKADGTP
760 770 780 790 800
WPAVGAGKRT TYGGVSGTAI RPIALRAVTT IARALPGFPI LATGGIDSAE
810 820 830 840 850
SGLQFLHSGA SVLQVCSAVQ NQDFTVIQDY CTGLKALLYL KSIEELQGWD
860 870 880 890 900
GQSPGTESHQ KGKPVPRIAE LMGKKLPNFG PYLEQRKKII AEEKMRLKEQ
910 920 930 940 950
NAAFPPLERK PFIPKKPIPA IKDVIGKALQ YLGTFGELSN IEQVVAVIDE
960 970 980 990 1000
EMCINCGKCY MTCNDSGYQA IQFDPETHLP TVTDTCTGCT LCLSVCPIID
1010 1020
CIRMVSRTTP YEPKRGLPLA VNPVC
Length:1,025
Mass (Da):111,424
Last modified:November 1, 1997 - v1
Checksum:iB8D553AD862845D0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.

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.
InParanoidi Q28943.
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: November 26, 2014
This is version 116 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