P05982 · NQO1_RAT

  • Protein
    NAD(P)H dehydrogenase [quinone] 1
  • Gene
    Nqo1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (PubMed:1703398, PubMed:7862630, PubMed:8999809).
Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (By similarity).
Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (By similarity).
Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (By similarity).

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.

Catalytic activity

Cofactor

FAD (UniProtKB | Rhea| CHEBI:57692 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
85 μMNADH
39 μMNADPH
110 μMNADH
2.5 μMmenadione
840 μM5-(aziridin-1-yl)-2,4-dinitrobenzamide
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
2400 μmol/min/mgtoward menadione
140 nmol/min/mgtoward 5-(aziridin-1-yl)-2,4-dinitrobenzamide
kcat is 0.075 min-1 NADH with as substrate. kcat is 0.074 min-1 with NADPH as substrate.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site12FAD (UniProtKB | ChEBI)
Binding site18-19FAD (UniProtKB | ChEBI)
Binding site67FAD (UniProtKB | ChEBI)
Binding site104-107FAD (UniProtKB | ChEBI)
Binding site126-128substrate
Binding site148-151FAD (UniProtKB | ChEBI)
Binding site156FAD (UniProtKB | ChEBI)
Binding site201FAD (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentneuronal cell body
Cellular Componentnucleus
Molecular Functionidentical protein binding
Molecular FunctionNAD(P)H dehydrogenase (quinone) activity
Molecular FunctionNADH:ubiquinone reductase (non-electrogenic) activity
Molecular FunctionNADPH dehydrogenase (quinone) activity
Molecular Functionsuperoxide dismutase activity
Biological Processcell redox homeostasis
Biological Processcellular response to hydrogen peroxide
Biological Processcellular response to metal ion
Biological Processcellular response to oxidative stress
Biological Processinnate immune response
Biological ProcessNADH oxidation
Biological ProcessNADPH oxidation
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of ferroptosis
Biological Processnegative regulation of protein catabolic process
Biological Processpositive regulation of neuron apoptotic process
Biological Processprotein catabolic process
Biological Processprotein polyubiquitination
Biological Processremoval of superoxide radicals
Biological Processresponse to alkaloid
Biological Processresponse to amine
Biological Processresponse to carbohydrate
Biological Processresponse to electrical stimulus
Biological Processresponse to estradiol
Biological Processresponse to ethanol
Biological Processresponse to flavonoid
Biological Processresponse to hormone
Biological Processresponse to hydrogen sulfide
Biological Processresponse to ischemia
Biological Processresponse to L-glutamine
Biological Processresponse to lipopolysaccharide
Biological Processresponse to nutrient
Biological Processresponse to organic cyclic compound
Biological Processresponse to oxidative stress
Biological Processresponse to testosterone
Biological Processresponse to tetrachloromethane
Biological Processresponse to xenobiotic stimulus
Biological Processsuperoxide metabolic process
Biological Processubiquinone metabolic process
Biological Processvitamin E metabolic process
Biological Processvitamin K metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    NAD(P)H dehydrogenase [quinone] 1
  • EC number
  • Alternative names
    • Azoreductase
    • DT-diaphorase
      (DTD)
    • Menadione reductase
    • NAD(P)H:quinone oxidoreductase 1
    • Phylloquinone reductase
    • Quinone reductase 1 (QR1)

Gene names

    • Name
      Nqo1
    • Synonyms
      Nmor1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P05982
  • Secondary accessions
    • Q63478

Proteomes

Organism-specific databases

Subcellular Location

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis105Decreases the catalytic efficiency toward menadione and nitrobenzene substrates.
Mutagenesis117-118Destroys enzyme activity.
Mutagenesis131Decreases the catalytic efficiency toward menadione. Has no effect on the catalytic efficiency toward nitrobenzene substrate.
Mutagenesis161Destroys enzyme activity.
Mutagenesis164Destroys enzyme activity.
Mutagenesis195Induces a very low catalytic efficiency.
Mutagenesis204Has no effect on the catalytic efficiency toward menadione and nitrobenzene substrates.
Mutagenesis219Has no effect on the catalytic efficiency toward menadione and nitrobenzene substrates.
Mutagenesis239Has no effect on the catalytic efficiency toward menadione. Slightly decreases the catalytic efficiency toward nitrobenzene substrate.

Chemistry

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, cross-link.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00000716252-274NAD(P)H dehydrogenase [quinone] 1
Modified residue82Phosphoserine
Cross-link251Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Keywords

Proteomic databases

PTM databases

Expression

Induction

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

Gene expression databases

Interaction

Subunit

Homodimer (PubMed:7568029).
Interacts with PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in response to oxidative stress and protects it from ubiquitin-independent degradation by the core 20S proteasome (By similarity).
Interacts with TP73 (via SAM domain); this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).
Interacts with TP53; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).

Protein-protein interaction databases

Chemistry

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region225-274Important for apoenzyme conformational stability

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    274
  • Mass (Da)
    30,947
  • Last updated
    2007-01-23 v4
  • Checksum
    40E8801320A20F09
MAVRRALIVLAHAERTSFNYAMKEAAVEALKKKGWEVVESDLYAMNFNPLISRNDITGEPKDSENFQYPVESSLAYKEGRLSPDIVAEQKKLEAADLVIFQFPLYWFGVPAILKGWFERVLVAGFAYTYATMYDKGPFQNKKTLLSITTGGSGSMYSLQGVHGDMNVILWPIQSGILRFCGFQVLEPQLVYSIGHTPPDARVQVLEGWKKRLETVWEESPLYFAPSSLFDLNFQAGFLLKKEVQEEQKKNKFGLSVGHHLGKSIPADNQIKARK

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8L2UJ69A0A8L2UJ69_RATNqo1256

Sequence caution

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

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict31in Ref. 9; AA sequence
Sequence conflict80in Ref. 10; X17464
Sequence conflict135in Ref. 3; AAA41988
Sequence conflict216in Ref. 9; AA sequence
Sequence conflict227in Ref. 9; AA sequence
Sequence conflict263in Ref. 9; AA sequence
Sequence conflict269in Ref. 11; AA sequence

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
J02608
EMBL· GenBank· DDBJ
AAA41716.1
EMBL· GenBank· DDBJ
mRNA
J02679
EMBL· GenBank· DDBJ
AAA41715.1
EMBL· GenBank· DDBJ
mRNA
M36660
EMBL· GenBank· DDBJ
AAA39829.1
EMBL· GenBank· DDBJ
mRNA
J02640
EMBL· GenBank· DDBJ
AAA41988.1
EMBL· GenBank· DDBJ
mRNA Different initiation
M31805
EMBL· GenBank· DDBJ
AAA41989.1
EMBL· GenBank· DDBJ
Genomic DNA
M31801
EMBL· GenBank· DDBJ
AAA41989.1
EMBL· GenBank· DDBJ
Genomic DNA
M31802
EMBL· GenBank· DDBJ
AAA41989.1
EMBL· GenBank· DDBJ
Genomic DNA
M31804
EMBL· GenBank· DDBJ
AAA41989.1
EMBL· GenBank· DDBJ
Genomic DNA
M33039
EMBL· GenBank· DDBJ
AAA41990.1
EMBL· GenBank· DDBJ
Genomic DNA
M33038
EMBL· GenBank· DDBJ
AAA41990.1
EMBL· GenBank· DDBJ
Genomic DNA
BC083542
EMBL· GenBank· DDBJ
AAH83542.1
EMBL· GenBank· DDBJ
mRNA
X17464
EMBL· GenBank· DDBJ
-mRNA No translation available.

Genome annotation databases

Similar Proteins

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