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FLASH GENE
Symbol DUOX2 contributors: mct/ - updated : 21-12-2017
HGNC name dual oxidase 2
HGNC id 13273
Corresponding disease
HTDI1 congenital hypothyroidism with defects in iodide organification 1
Location 15q21.1      Physical location : 45.384.852 - 45.406.359
Synonym name
  • thyroid oxidase 2
  • NADPH oxidase/peroxidase DUOX2
  • NADH/NADPH thyroid oxidase p138-tox
  • weakly similar to stromal cell-derived factor 2
  • nicotinamide adenine dinucleotide phosphate oxidase
  • Synonym symbol(s) P138, P138-TOX, THOX2, NOXEF2, LNOX2
    EC.number 1.6.3.1, 1.11.1.-
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    text arranged head-to-head to DUOXA2
    STRUCTURE 21.51 kb     34 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • genomic region between the translation start sites of DUOX2 and DUOXA2 functions as a bidirectional promoter in human airway tissue
  • MAPPING cloned Y linked N status confirmed
    Physical map
    GRP58 15q15 glucose regulated protein, 58kDa ELL3 15q15.1 elongation factor RNA polymerase II-like 3 SERF2 15q13.1 small EDRK-rich factor 2 HYPK 15q14 small EDRK-rich factor 2 MFAP1 15q15-q21 microfibrillar-associated protein 1 FLJ12973 15q15.1 hypothetical protein FLJ12973 MGC14161 15q15.1 hypothetical protein MGC14161 ACTBP7 15q15.3 actin, beta pseudogene 7 H63 15q15.1 H63 breast cancer expressed gene HSPC129 15q15.1 hypothetical protein HSPC129 EIF3S1 15q15.3 eukaryotic translation initiation factor 3, subunit 1 alpha, 35kDa FLJ21439 15q14 hypothetical protein FLJ21439 LOC197135 15q15.1 similar to RIKEN cDNA 4930424G05 B2M 15q21-q22.2 beta-2-microglobulin RNF36 15q14 ring finger protein 36 LOC116166 15q15.1 similar to Sorbitol dehydrogenase (L-iditol 2-dehydrogenase) MGC33951 15q15.1 hypothetical protein MGC33951 SORD 15q15 sorbitol dehydrogenase DUOX2 15q15.3-q21 dual oxidase 2 FLJ32334 15q15.1 hypothetical protein FLJ32334 DUOX1 15q15.3-q21 dual oxidase 1 LOC90525 15q15.1 hypothetical protein BC007586 SLC28A2 15q15 solute carrier family 28 (sodium-coupled nucleoside transporter), member 2 GATM 15q14.2 glycine amidinotransferase (L-arginine:glycine amidinotransferase) MGC5347 15q15.1 hypothetical protein MGC5347 NMES1 15q15.1 normal mucosa of esophagus specific 1 SLC30A4 15q15-q21.1 solute carrier family 30 (zinc transporter), member 4 FLJ39426 15q15.1 hypothetical protein FLJ39426 PLDN 15q14 pallidin homolog (mouse) SQRDL 15q15 sulfide quinone reductase-like (yeast) LOC145660 15q15.1 hypothetical LOC145660
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    34 - 6428 175 1548 - 2000 10806195
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     mouth   highly
    Endocrinethyroid    
    Respiratoryrespiratory tract     Homo sapiens
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticthymocyte
    Endocrineislet cell (alpha,beta...)
    Endocrinethyroid cell
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extended N terminal containing two EF-hand motifs, a unique extracellular N-terminal region
  • a peroxidase homology domain
  • an oxido-reductase FAD/NAD-binding domain
  • HOMOLOGY
    interspecies homolog to rattus Duox2 (84.25 pc)
    homolog to murine Duox2 (85.63 pc)
    intraspecies homolog to phagocyte gp91phox/Nox2 NADPH-dependent
    Homologene
    FAMILY
  • NADH oxidase family
  • peroxidase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • apical membrane of the thyrocyte
  • completely retained in the ER
  • functional DUOX1 and DUOX2 localize to the leading edge of migrating cells, augmenting motility and wound healing
  • basic FUNCTION
  • catalyzing the synthesis of thyroid hormone
  • essential for iodination of thyroglobulin by thyroid peroxidase and constitutes the rate-limiting step of thyroid hormone synthesis
  • dual oxydase constitute the catalytic core of the H2O2 generator
  • exhibiting potent heme peroxidase activity in human respiratory tract epithelium
  • NADPH oxidases producing H(2)O(2) necessary for thyroid hormone biosynthesis
  • with NOX4, are required for platelet-derived growth factor (PDGF) induced RB1 phosphorylation in normal fibroblasts
  • NOX4 and DUOX2 regulate cell cycle entry as part of a p53-dependent checkpoint for proliferation
  • 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
  • despite the high sequence similarity shared between DUOX1 and DUOX2, the two isoforms present distinct regulations, tissue expression and catalytic functions
  • both DUOX2 and DUOXA2 expression are involved specifically in inflammation and are regulated on a crypt-by-crypt basis in ulcerative colitis tissue
  • both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like function with respect to its partner
  • 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
  • thyroid hormone synthesis requires H2O2, produced by two NADPH oxidases, DUOX1 and DUOX2
  • H2O2 produced by the DUOX2/DUOXA2 cell surface enzymatic complex could provoke potential mutagenic DNA damage in an inducible cellular model
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text differentiation marker of thyrocytes
    PATHWAY
    metabolism
    signaling
    thyroid hormone biosynthesis
    a component
  • this complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes this encoded protein and DUOX1 and DUOX2
  • component of the thyroid H(2)O(2) generator crucial for hormone synthesis at the apical membrane
  • DUOX1 and DUOX2 constitute the major components of the thyroid H(2)O(2)-generating system required for thyroid hormone synthesis
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • Ca2+
  • Fe2+
  • FAD
  • NAD
  • protein
  • DUOXA2
  • TPO presents a catalase-like effect that protects DUOX1 and DUOX2 from inhibition by H2O2
  • thyroid hydrogen peroxide production is enhanced by the Th2 cytokines, IL4 and IL13, through increased expression of the DUOX2 and its maturation factor DUOXA2
  • the maturation and activity of DUOX2 were drastically impaired when expressed with the glycosylation-defective maturation factor DUOXA2
  • cell & other
    REGULATION
    Other IFNG mediates DUOX2 expression in respiratory tract epithelium via a STAT-independent signaling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s) HTDI1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional somatic mutation      
    Missense mutations (Q36H, R376W, D506N) of dual oxidase 2 (DUOX2) implicated in congenital hypothyroidism have impaired trafficking in cells reconstituted with DUOX2 maturation factor
    tumoral     --low  
    by promoter hypermethylation in lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS