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Protein

NAD(P)H dehydrogenase [quinone] 1

Gene

Nqo1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.2 Publications

Catalytic activityi

NAD(P)H + a quinone = NAD(P)+ + a hydroquinone.2 Publications

Cofactori

FAD1 Publication

Kineticsi

kcat is 0.075 min(-1) NADH with as substrate. kcat is 0.074 min(-1) with NADPH as substrate.1 Publication

  1. KM=85 µM for NADH1 Publication
  2. KM=39 µM for NADPH1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei12 – 121FAD1 Publication
    Binding sitei67 – 671FAD1 Publication
    Binding sitei156 – 1561FAD1 Publication
    Binding sitei201 – 2011FAD1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi18 – 192FAD1 Publication
    Nucleotide bindingi104 – 1074FAD1 Publication
    Nucleotide bindingi148 – 1514FAD1 Publication

    GO - Molecular functioni

    • NAD(P)H dehydrogenase (quinone) activity Source: RGD
    • poly(A) RNA binding Source: Ensembl
    • superoxide dismutase activity Source: RGD

    GO - Biological processi

    • aging Source: RGD
    • negative regulation of apoptotic process Source: RGD
    • negative regulation of catalytic activity Source: Ensembl
    • positive regulation of neuron apoptotic process Source: RGD
    • removal of superoxide radicals Source: GOC
    • response to estradiol Source: RGD
    • response to ethanol Source: RGD
    • response to nutrient Source: RGD
    • response to organic cyclic compound Source: RGD
    • response to oxidative stress Source: RGD
    • superoxide metabolic process Source: RGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    FAD, Flavoprotein, NAD, NADP

    Enzyme and pathway databases

    BRENDAi1.6.5.2. 5301.
    ReactomeiR-RNO-350562. Regulation of ornithine decarboxylase (ODC).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD(P)H dehydrogenase [quinone] 1 (EC:1.6.5.22 Publications)
    Alternative name(s):
    Azoreductase
    DT-diaphorase
    Short name:
    DTD
    Menadione reductase
    NAD(P)H:quinone oxidoreductase 1
    Phylloquinone reductase
    Quinone reductase 1
    Short name:
    QR1
    Gene namesi
    Name:Nqo1
    Synonyms:Nmor1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 19

    Organism-specific databases

    RGDi2503. Nqo1.

    Subcellular locationi

    • Cytoplasm 1 Publication

    GO - Cellular componenti

    • cytosol Source: RGD
    • extracellular exosome Source: Ensembl
    • neuronal cell body Source: RGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi117 – 1182FE → KK: Destroys enzyme activity. 1 Publication
    Mutagenesisi161 – 1611V → D: Destroys enzyme activity. 1 Publication
    Mutagenesisi164 – 1641D → Q: Destroys enzyme activity. 1 Publication
    Mutagenesisi195 – 1951H → A: Induces a very low catalytic efficiency. 1 Publication

    Chemistry

    ChEMBLiCHEMBL3091269.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemoved2 Publications
    Chaini2 – 274273NAD(P)H dehydrogenase [quinone] 1PRO_0000071625Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP05982.
    PRIDEiP05982.

    2D gel databases

    World-2DPAGE0004:P05982.

    PTM databases

    iPTMnetiP05982.
    PhosphoSiteiP05982.

    Expressioni

    Inductioni

    By polycyclic hydrocarbons (Governed by the aromatic hydrocarbon-responsive (AH) locus).

    Gene expression databases

    GenevisibleiP05982. RN.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    IntActiP05982. 1 interaction.
    STRINGi10116.ENSRNOP00000017175.

    Structurei

    Secondary structure

    1
    274
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 106Combined sources
    Helixi18 – 3215Combined sources
    Beta strandi36 – 416Combined sources
    Turni42 – 465Combined sources
    Helixi53 – 553Combined sources
    Helixi68 – 7811Combined sources
    Helixi83 – 9412Combined sources
    Beta strandi96 – 1038Combined sources
    Helixi111 – 12010Combined sources
    Turni123 – 1253Combined sources
    Helixi133 – 1353Combined sources
    Turni137 – 1404Combined sources
    Beta strandi142 – 1487Combined sources
    Helixi153 – 1564Combined sources
    Helixi165 – 1739Combined sources
    Helixi174 – 1785Combined sources
    Turni179 – 1813Combined sources
    Beta strandi188 – 1903Combined sources
    Helixi193 – 1953Combined sources
    Helixi198 – 21215Combined sources
    Helixi215 – 2173Combined sources
    Helixi226 – 2283Combined sources
    Turni233 – 2364Combined sources
    Helixi241 – 2477Combined sources
    Beta strandi254 – 2563Combined sources
    Turni266 – 2705Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1QRDX-ray2.40A/B2-274[»]
    ProteinModelPortaliP05982.
    SMRiP05982. Positions 2-274.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05982.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni126 – 1283Substrate bindingBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IKWF. Eukaryota.
    COG2249. LUCA.
    GeneTreeiENSGT00440000033410.
    HOGENOMiHOG000149970.
    HOVERGENiHBG029104.
    InParanoidiP05982.
    KOiK00355.
    OMAiYDKGPFQ.
    OrthoDBiEOG7CZK6F.
    PhylomeDBiP05982.
    TreeFamiTF300296.

    Family and domain databases

    Gene3Di3.40.50.360. 1 hit.
    InterProiIPR003680. Flavodoxin_fold.
    IPR029039. Flavoprotein-like_dom.
    [Graphical view]
    PfamiPF02525. Flavodoxin_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52218. SSF52218. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P05982-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAVRRALIVL AHAERTSFNY AMKEAAVEAL KKKGWEVVES DLYAMNFNPL
    60 70 80 90 100
    ISRNDITGEP KDSENFQYPV ESSLAYKEGR LSPDIVAEQK KLEAADLVIF
    110 120 130 140 150
    QFPLYWFGVP AILKGWFERV LVAGFAYTYA TMYDKGPFQN KKTLLSITTG
    160 170 180 190 200
    GSGSMYSLQG VHGDMNVILW PIQSGILRFC GFQVLEPQLV YSIGHTPPDA
    210 220 230 240 250
    RVQVLEGWKK RLETVWEESP LYFAPSSLFD LNFQAGFLLK KEVQEEQKKN
    260 270
    KFGLSVGHHL GKSIPADNQI KARK
    Length:274
    Mass (Da):30,947
    Last modified:January 23, 2007 - v4
    Checksum:i40E8801320A20F09
    GO

    Sequence cautioni

    The sequence AAA41988.1 differs from that shown. Reason: Erroneous initiation. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti31 – 311Missing AA sequence (PubMed:3144286).Curated
    Sequence conflicti80 – 801R → G in X17464 (PubMed:2504488).Curated
    Sequence conflicti135 – 1351K → Q in AAA41988 (PubMed:3100515).Curated
    Sequence conflicti216 – 2161W → E AA sequence (PubMed:3144286).Curated
    Sequence conflicti227 – 2271S → E AA sequence (PubMed:3144286).Curated
    Sequence conflicti263 – 2631S → I AA sequence (PubMed:3144286).Curated
    Sequence conflicti269 – 2691Q → E AA sequence (PubMed:2499768).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02608 mRNA. Translation: AAA41716.1.
    J02679 mRNA. Translation: AAA41715.1.
    M36660 mRNA. Translation: AAA39829.1.
    J02640 mRNA. Translation: AAA41988.1. Different initiation.
    M31805
    , M31801, M31802, M31804 Genomic DNA. Translation: AAA41989.1.
    M33039, M33038 Genomic DNA. Translation: AAA41990.1.
    BC083542 mRNA. Translation: AAH83542.1.
    X17464 mRNA. No translation available.
    PIRiA34162.
    RefSeqiNP_058696.2. NM_017000.3.
    UniGeneiRn.11234.

    Genome annotation databases

    EnsembliENSRNOT00000017174; ENSRNOP00000017175; ENSRNOG00000012772.
    GeneIDi24314.
    KEGGirno:24314.
    UCSCiRGD:2503. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J02608 mRNA. Translation: AAA41716.1.
    J02679 mRNA. Translation: AAA41715.1.
    M36660 mRNA. Translation: AAA39829.1.
    J02640 mRNA. Translation: AAA41988.1. Different initiation.
    M31805
    , M31801, M31802, M31804 Genomic DNA. Translation: AAA41989.1.
    M33039, M33038 Genomic DNA. Translation: AAA41990.1.
    BC083542 mRNA. Translation: AAH83542.1.
    X17464 mRNA. No translation available.
    PIRiA34162.
    RefSeqiNP_058696.2. NM_017000.3.
    UniGeneiRn.11234.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1QRDX-ray2.40A/B2-274[»]
    ProteinModelPortaliP05982.
    SMRiP05982. Positions 2-274.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiP05982. 1 interaction.
    STRINGi10116.ENSRNOP00000017175.

    Chemistry

    ChEMBLiCHEMBL3091269.

    PTM databases

    iPTMnetiP05982.
    PhosphoSiteiP05982.

    2D gel databases

    World-2DPAGE0004:P05982.

    Proteomic databases

    PaxDbiP05982.
    PRIDEiP05982.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000017174; ENSRNOP00000017175; ENSRNOG00000012772.
    GeneIDi24314.
    KEGGirno:24314.
    UCSCiRGD:2503. rat.

    Organism-specific databases

    CTDi1728.
    RGDi2503. Nqo1.

    Phylogenomic databases

    eggNOGiENOG410IKWF. Eukaryota.
    COG2249. LUCA.
    GeneTreeiENSGT00440000033410.
    HOGENOMiHOG000149970.
    HOVERGENiHBG029104.
    InParanoidiP05982.
    KOiK00355.
    OMAiYDKGPFQ.
    OrthoDBiEOG7CZK6F.
    PhylomeDBiP05982.
    TreeFamiTF300296.

    Enzyme and pathway databases

    BRENDAi1.6.5.2. 5301.
    ReactomeiR-RNO-350562. Regulation of ornithine decarboxylase (ODC).

    Miscellaneous databases

    EvolutionaryTraceiP05982.
    NextBioi602959.
    PROiP05982.

    Gene expression databases

    GenevisibleiP05982. RN.

    Family and domain databases

    Gene3Di3.40.50.360. 1 hit.
    InterProiIPR003680. Flavodoxin_fold.
    IPR029039. Flavoprotein-like_dom.
    [Graphical view]
    PfamiPF02525. Flavodoxin_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52218. SSF52218. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "NAD(P)H:menadione oxidoreductase. Novel purification of enzyme cDNA and complete amino acid sequence, and gene regulation."
      Robertson J.A., Chen H.-C., Nebert D.W.
      J. Biol. Chem. 261:15794-15799(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. "Autoregulation plus positive and negative elements controlling transcription of genes in the [Ah] battery."
      Robertson J.A., Nebert D.W., Hankinson O.
      Chem. Scr. 27:83-87(1987)
      Cited for: NUCLEOTIDE SEQUENCE.
    3. "Rat liver NAD(P)H: quinone reductase nucleotide sequence analysis of a quinone reductase cDNA clone and prediction of the amino acid sequence of the corresponding protein."
      Bayney R.M., Rodkey J.A., Bennett C.D., Lu A.Y.H., Pickett C.B.
      J. Biol. Chem. 262:572-575(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    4. "Rat liver NAD(P)H:quinone reductase. Regulation of quinone reductase gene expression by planar aromatic compounds and determination of the exon structure of the quinone reductase structural gene."
      Bayney R.M., Morton M.R., Favreau L.V., Pickett C.B.
      J. Biol. Chem. 264:21793-21797(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE.
      Tissue: Liver.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Heart.
    6. "Structure-function relationship of NAD(P)H:quinone reductase: characterization of NH2-terminal blocking group and essential tyrosine and lysine residues."
      Haniu M., Yuan H., Chen S.A., Iyanagi T., Lee T.D., Shively J.E.
      Biochemistry 27:6877-6883(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-274, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2.
    7. "Rat liver NAD(P)H:quinone reductase: isolation of a quinone reductase structural gene and prediction of the NH2 terminal sequence of the protein by double-stranded sequencing of exons 1 and 2."
      Bayney R.M., Pickett C.B.
      Arch. Biochem. Biophys. 260:847-850(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 1-57.
    8. "Expression of mammalian DT-diaphorase in Escherichia coli: purification and characterization of the expressed protein."
      Ma Q., Wang R., Yang C.S., Lu A.Y.H.
      Arch. Biochem. Biophys. 283:311-317(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-21, FUNCTION, COFACTOR, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
    9. "The nitroreductase enzyme in Walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2)."
      Knox R.J., Boland M.P., Friedlos F., Coles B., Southan C., Roberts J.J.
      Biochem. Pharmacol. 37:4671-4677(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 24-131 AND 156-270.
    10. "Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells."
      Dear T.N., McDonald D.A., Kefford R.F.
      Cancer Res. 49:5323-5328(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 80-274.
    11. "Reaction of rat liver DT-diaphorase (NAD(P)H:quinone acceptor reductase) with 5'-[p-(fluorosulfonyl)benzoyl]-adenosine."
      Liu X.F., Yuan H., Haniu M., Iyanagi T., Shively J.E., Chen S.A.
      Mol. Pharmacol. 35:818-822(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 147-156 AND 263-271.
    12. "Rat liver NAD(P)H:quinone oxidoreductase: cDNA expression and site-directed mutagenesis."
      Forrest G.L., Qian J., Ma J.-X., Kaplan W.D., Akman S., Doroshow J., Chen S.A.
      Biochem. Biophys. Res. Commun. 169:1087-1093(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS.
    13. "Subunit functional studies of NAD(P)H:quinone oxidoreductase with a heterodimer approach."
      Cui K., Lu A.Y., Yang C.S.
      Proc. Natl. Acad. Sci. U.S.A. 92:1043-1047(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-195.
    14. "The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction."
      Li R., Bianchet M.A., Talalay P., Amzel L.M.
      Proc. Natl. Acad. Sci. U.S.A. 92:8846-8850(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FAD AND DUROQUINONE, SUBUNIT.
      Tissue: Liver.
    15. Erratum
      Li R., Bianchet M.A., Talalay P., Amzel L.M.
      Proc. Natl. Acad. Sci. U.S.A. 92:10815-10815(1995)

    Entry informationi

    Entry nameiNQO1_RAT
    AccessioniPrimary (citable) accession number: P05982
    Secondary accession number(s): Q63478
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: January 23, 2007
    Last modified: April 13, 2016
    This is version 146 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Quinone reductase accepts electrons from both NADH and NADPH with equal efficiency.
    This protein is inhibited by dicoumarol.

    Caution

    PubMed:2480957 sequence seems incorrectly to be attributed to a mouse sequence while it really seems to correspond to the rat sequence.Curated

    Keywords - Technical termi

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

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    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.