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FLASH GENE

Symbol

DUOX1

contributors: mct/npt - updated : 21-12-2017

HGNC name	dual oxidase 1
HGNC id	3062

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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	1.6.3.1, 1.11.1.-

DNA

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_017434 35 - 5693 NP_059130 177.23 1551 - 2018 28982074 NM_175940 34 splicing 5501 NP_787954 177.23 1551 - 2018 28982074

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       moderately   mouth tongue     highly   pharynx       moderately Endocrine thyroid       predominantly Respiratory respiratory tract trachea     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cells

System Cell Pubmed Species Stage Rna symbol Respiratory epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	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

HOMOLOGY

interspecies	homolog to rattus Duox1 (90.43 pc)
	homolog to murine Duox1 (90.89 pc)

Homologene

FAMILY

NADPH oxidase family

CATEGORY

chaperone/stress , enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	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

PHYSIOLOGICAL PROCESS

text	differentiation marker of thyrocytes

PATHWAY

metabolism

signaling

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

INTERACTION

DNA

RNA

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

REGULATION

activated by

extracellular ATP and purinergic receptor stimulation (Boots 2009)

ASSOCIATED DISORDERS

corresponding disease(s)

HTDI3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by promoter hypermethylation in lung cancer (Luxen 2008) tumoral     --low   in lung and liver cancers tumoral         silenced in breast cancer, which seems to be involved in breast carcinogenesis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	DUOX1 expression in liver tumors is a potential prognostic tool for patients
Therapy target

ANIMAL & CELL MODELS