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Q28943

- DPYD_PIG

UniProt

Q28943 - DPYD_PIG

Protein

Dihydropyrimidine dehydrogenase [NADP(+)]

Gene

DPYD

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Nov 1997)
      Previous versions | rss
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    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.
    FAD.
    FMN.

    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 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

    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

    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 – 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.
    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.
    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: October 1, 2014
    This is version 114 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