NAD(P)H dehydrogenase [quinone] 1
Also known as: DIA4, NMOR1, NQO1
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 (By similarity). 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. Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential. 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.
Classification
- Family (Pfam)
- PF02525 Flavodoxin_2
- InterPro
- Flavodoxin_fold, Flavoprotein-like_sf, NAD(P)H_dehydrogenase_qn
- Functional cluster
- Nucleotide & Amino-Acid Biosynthesis Enzymes
Experimental structures · PDB · 27
- 1D4A X-ray 1.70A
- 1DXO X-ray 2.50A
- 1GG5 X-ray 2.50A
- 1H66 X-ray 2.00A
- 1H69 X-ray 1.86A
- 1KBO X-ray 2.30A
- 1KBQ X-ray 1.80A
- 1QBG X-ray 2.30A
- 2F1O X-ray 2.75A
- 3JSX X-ray 2.45A
- 4CET X-ray 2.20A
- 4CF6 X-ray 2.69A
- … and 15 more
A predicted model is available from AlphaFold.
Gene Ontology · 27
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005634 nucleus
- GO:0045202 synapse
- GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H
- GO:0042802 identical protein binding
- GO:0003955 NAD(P)H dehydrogenase (quinone) activity
- GO:0050136 NADH dehydrogenase (quinone) (non-electrogenic) activity
- GO:0008753 NADPH dehydrogenase (quinone) activity
- GO:0003723 RNA binding
- GO:0045454 cell redox homeostasis
- GO:0034599 cellular response to oxidative stress
- GO:0045087 innate immune response
- GO:0110076 negative regulation of ferroptosis
- GO:0042177 negative regulation of protein catabolic process
- GO:0006809 nitric oxide biosynthetic process
- GO:0030163 protein catabolic process
- GO:0000209 protein polyubiquitination
- GO:0019430 removal of superoxide radicals
- GO:0032496 response to lipopolysaccharide
- GO:0006979 response to oxidative stress
- GO:0009636 response to toxic substance
- GO:0007271 synaptic transmission, cholinergic
- GO:0006743 ubiquinone metabolic process
- GO:0042360 vitamin E metabolic process
- GO:0042373 vitamin K metabolic process
- GO:0006805 xenobiotic metabolic process
Drugs targeting this protein · 1
- VATIQUINONE modulator
Related proteins · sequence + function similarity
- NAD(P)H dehydrogenase [quinone] 1 1.00
- NAD(P)H dehydrogenase [quinone] 1 0.98
- NAD(P)H dehydrogenase [quinone] 1 0.97
- NAD(P)H dehydrogenase [quinone] 1 0.97
- Ribosyldihydronicotinamide dehydrogenase [quinone] 0.88
- Ribosyldihydronicotinamide dehydrogenase [quinone] 0.86
- Ribosyldihydronicotinamide dehydrogenase [quinone] 0.85
- Ribosyldihydronicotinamide dehydrogenase [quinone] 0.83
- Ribosyldihydronicotinamide dehydrogenase-like protein traD 0.64
- NADPH:quinone oxidoreductase MdaB 0.58
- NADPH:quinone oxidoreductase MdaB 0.58
- NADPH:quinone oxidoreductase MdaB 0.58
Co-cited proteins · studied together in the literature
- NAD(P)H dehydrogenase [quinone] 1 2 shared papers
- NAD(P)H dehydrogenase [quinone] 1 1 shared papers
- PDZ and LIM domain protein 4 1 shared papers
- Tumor protein p73 1 shared papers
- Cellular tumor antigen p53 1 shared papers
Literature · 21 cited papers
- Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism. Sci. Rep. · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Actin cytoskeleton remodeling by the alternatively spliced isoform of PDLIM4/RIL protein. J. Biol. Chem. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol. Biochemistry · 2006
- A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev. · 2005
- The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger. Mol. Pharmacol. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches. Biochemistry · 2001
- … and 9 more in the literature graph