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FLASH GENE
Symbol NQO1 contributors: mct/npt - updated : 04-07-2023
HGNC name NAD(P)H dehydrogenase, quinone 1
HGNC id 2874
Location 16q22.1      Physical location : 69.743.304 - 69.760.533
Synonym name
  • NAD(P)H menadione oxidoreductase
  • diaphorase (NAD(P)H), cytochrome b-5 reductase
  • azoreductase
  • phylloquinone reductase
  • dioxin-inducible 1
  • Synonym symbol(s) NMOR1, DIA4, DTD, QR1, DHQU
    EC.number 1.6.5.2
    DNA
    TYPE functioning gene
    STRUCTURE 17.16 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2601 - 274 - 2000 10908561
    5 - 2499 - 240 - 2000 10908561
    5 - 2487 - 236 - 2000 10908561
    4 - 2305 - 202 - 200 10908561
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     liver   highly
     mouth   highly
    Lymphoid/Immunelymph node    
    Respiratorylung    
    Skin/Tegumentskin   highly
    Urinarykidney    
    Visualeyeanterior segment   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four potential polyadenylation sites
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • NAD(P)H dehydrogenase (quinone) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus, and also associated with mitotic spindles in cells undergoing division
  • basic FUNCTION
  • involved in detoxification pathways as well as in biosynthetic processes such as the vitamin k-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis
  • may be involved in nitric oxide biosynthesis, response to toxin, synaptic transmission, cholinergic, xenobiotic metabolism
  • plays a role in suppressing inflammatory response and in attenuation of macrophage migration induced by LPS
  • belongs to the phase II detoxifying enzymes that are induced to protect against electrophilic insults, oxidative stress, and ionizing radiation
  • original role in the regulation of mRNA translation via the control of EIF4GI stability by the proteasome
  • rescue proteins containing intrinsically unstructured domains, such as TP53 and TP73, from degradation by the 20S proteasome
  • FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones
  • NQO1, a cellular redox sensor, is linked to the metabolite-sensing network that tunes PPARGC1A expression and activity in regulating energy metabolism
  • plays a key role in suppressing ionizing radiation (IR)-induced centrosome amplification and aneuploidy through a direct interaction with Aurora-A
  • xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues
  • NQO1 may likely function as a redox-dependent molecular switch
  • NQO1/SREBF1 axis promoted the progression and metastasis of Hepatocellular carcinoma (HCC)
  • novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on FOS/CKS1 signaling
  • NQO1 protects cells from oxidative stress and damage caused by toxic quinones
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS detoxification
    text dependent two-electrons reduction of quinones derived from the oxidation of phenolic metabolites of benzene
    PATHWAY
    metabolism drug
    signaling
    a component
  • SQSTM1-NFE2L2-NQO1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • FAD
  • protein
  • REXO4 is involved in the activation of NQO1 gene activity, enhanced in the presence of ESR2
  • interacting with PDLIM4
  • NQO1 binds and protects PPARGC1A from degradation in an NADH-dependent manner
  • function of NQO1 in the oxygen-sensing mechanism that regulates HIF1A stability in cancers
  • NQO1 interacts with and activates SIRT2 in an NAD-dependent manner
  • SIRT1 and NQO1 form likely a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress
  • NQO1 directly interacts with the unstructured DNA-binding domain of FOS, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival
  • NQO1 alleviates diabetes-induced renal inflammation and fibrosis by regulating the TLR4/NFKB1 and TGFB1/Smad signaling pathways
  • cell & other
    REGULATION
    induced by dioxine
    dicoumarol
    repressed by TCF7L1
    Other regulated by NFE2L2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in tardive dyskinesia
    tumoral     --over  
    associated with breast cancer progression
    constitutional     --over  
    in the early and intermediate stages of Parkinson's disease (PD) and disappeared in the end-stage PD
    Susceptibility
  • to benzene toxicity
  • modifying the susceptibility to acute myeloid leukemia
  • to various forms of cancer
  • to breast cancer with poor survival
  • to artery plaques in type 2 diabetic patients
  • Variant & Polymorphism other
  • Cb09T TT phenotype with no NQO1 activity (susceptible)
  • allele 2 and 3 increases the risk of ALL
  • an increased risk of hematotoxicity after exposure to benzene
  • homozygote missense variant increasing the risk of breast cancer with poor survival
  • C609T polymorphism is associated with carotid artery plaques in type 2 diabetic patients (Han 2009)
  • Candidate gene prognostic and predictive marker for breast cancer
    Marker
  • may be a potential biomarker for poor prognostic evaluation of breast cancers
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    might be a potential therapeutic target for HCC
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    blockade of AKT1-mediated NQO1 degradation may ameliorate PD pathogenesis
    ANIMAL & CELL MODELS