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Symbol DUOX1 contributors: mct/npt - updated : 21-12-2017
HGNC name dual oxidase 1
HGNC id 3062
Corresponding disease
HTDI3 congenital hypothyroidism with defects in iodide organification 3
Location 15q21.1      Physical location : 45.422.191 - 45.457.774
Synonym name
  • NADPH thyroid oxidase 1
  • flavoprotein NADPH oxidase
  • nicotinamide adenine dinucleotide phosphate oxidase
  • large NOX 1
  • long NOX 1
  • Synonym symbol(s) THOX1, NOXEF1, LNOX1, MGC138840, MGC138841, DUOX
    EC.number, 1.11.1.-
    TYPE functioning gene
    STRUCTURE 35.58 kb     35 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    35 - 5693 177.23 1551 - 2018 28982074
    34 splicing 5501 177.23 1551 - 2018 28982074
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   moderately
     mouthtongue  highly
     pharynx   moderately
    Endocrinethyroid   predominantly
    Respiratoryrespiratory tracttrachea  highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • an extended N terminal containing EF-hand, N-terminal peroxidase-like domain, a unique extracellular N-terminal region
  • a calcium binding motifs
  • an oxido-reductase FAD/NAD-binding domain
  • a gp91 phox domain
  • conjugated GlycoP
    interspecies homolog to rattus Duox1 (90.43 pc)
    homolog to murine Duox1 (90.89 pc)
  • NADPH oxidase family
  • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • apical membrane of thyrocytes
  • functional DUOX1 and DUOX2 localize to the leading edge of migrating cells, augmenting motility and wound healing (Luxen 2009)
  • basic FUNCTION
  • basic thyroid H202 generating system with DUOX2
  • involved in mucin induction
  • involved in innate airway host defense through enhanced production of H2O2 (Boots 2009)
  • both DUOX1 and DUOX2 play a critical role in the production of H2O2 in the thyroid gland, which is the limiting factor in thyroglobulin iodination and thyroxine synthesis
  • activation results in the activation of ERK1/2 and NF-KappaB pathways, ADAM17 activation, EGFR ligand shedding leading to amplified epithelial EGFR activation and IL-8 production (Boots 2009)
  • either has a unique function or must interact with other protein factors to express its catalytic activity (Meitzler 2009)
  • also involved in thyroid hormonogenesis (Rigutto 20009)
  • despite the high sequence similarity shared between DUOX1 and DUOX2, the two isoforms present distinct regulations, tissue expression and catalytic functions
  • plays an important role in innate airway epithelial responses to infection or injury
  • importance of DUOX1 in epithelial redox signaling through reversible S-glutathionylation of a range of proteins, including proteins involved in cytoskeletal regulation and MAPK signaling pathways involved in cell migration
  • DUOX1-dependent H2O2 production, which induces DNA double-strand breaks, can cause genomic instability and promote the generation of neoplastic cells through its mutagenic effect
  • changes of intracellular calcium concentration are transformed into redox signals through the calcium-dependent activation of DUOX1
  • DUOX1 and CYBB play Distinct roles in Redox regulation of epidermal growth factor receptor signaling
  • both DUOX enzymes (DUOX1, DUOX2) and their respective maturation factors DUOXA1 and DUOXA2 form a stable complex at the cell surface, which is fundamental for their enzymatic activity
  • is an H2O2-generating enzyme related to a wide range of biological features, such as hormone synthesis, host defense, cellular proliferation, and fertilization
  • thyroid hormone synthesis requires H2O2, produced by two NADPH oxidases, DUOX1 and DUOX2
  • CELLULAR PROCESS cell life, differentiation
    text differentiation marker of thyrocytes
    a component
  • complex containing an iodide transporter, thyroperoxidase, and a peroxide generating system that includes DUOX1 and DUOX2
  • DUOX1 and DUOX2 constitute the major components of the thyroid H(2)O(2)-generating system required for thyroid hormone synthesis
  • DUOX1 dimerization is required for stability to achieve the correct structure or interaction with its maturation factor, DUOXA1
  • an intermolecular disulfide bridge rather than an intramolecular disulfide bridge is important for both the trafficking and H2O2-generating activity of the DUOX1-DUOXA1 complex
    small molecule metal binding, other,
  • Ca2+
  • NAPD
  • Fe2+
  • protein
  • DUOXA1
  • TPO presents a catalase-like effect that protects DUOX1 and DUOX2 from inhibition by H2O2
  • novel role of IL4/IL13-induced DUOX1 expression in making a positive feedback loop for IL4/IL13 signaling in keratinocytes
  • direct interaction of DUOX1 and its DUOXA1 maturation factor occurs through contact of cysteine residue(s) in their extracellular domains
  • testosterone stimulates DUOX1 activity through GPRC6A in skin keratinocytes
  • PDGFA-induced migration of mesenchymal cells requires NOX4 and DUOX1/2 enzymes, which mediate redox-sensitive activation of PI3-kinase pathway and PKB/AKT1
  • autophagy regulates DUOX1 localization and superoxide production in airway epithelial cells during chronic IL13 stimulation
  • regulates primary B cell function under the influence of IL4 through BCR-mediated generation of hydrogen peroxide
  • cell & other
    activated by extracellular ATP and purinergic receptor stimulation (Boots 2009)
    corresponding disease(s) HTDI3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by promoter hypermethylation in lung cancer (Luxen 2008)
    tumoral     --low  
    in lung and liver cancers
    silenced in breast cancer, which seems to be involved in breast carcinogenesis
    Variant & Polymorphism
    Candidate gene
  • DUOX1 expression in liver tumors is a potential prognostic tool for patients
  • Therapy target