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Dual oxidase 2

From Wikipedia, the free encyclopedia
DUOX2
Identifiers
AliasesDUOX2, LNOX2, NOXEF2, P138-TOX, TDH6, THOX2, dual oxidase 2
External IDsOMIM: 606759; MGI: 3036280; HomoloGene: 9689; GeneCards: DUOX2; OMA:DUOX2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

50506

214593

Ensembl

ENSG00000140279

ENSMUSG00000068452

UniProt

Q9NRD8

A2AQ99

RefSeq (mRNA)

NM_014080
NM_001363711

NM_177610
NM_001362755

RefSeq (protein)

NP_054799
NP_001350640

NP_808278
NP_001349684

Location (UCSC)Chr 15: 45.09 – 45.11 MbChr 2: 122.11 – 122.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Dual oxidase 2, also known as DUOX2 or ThOX2 (for thyroid oxidase), is an enzyme that in humans is encoded by the DUOX2 gene.[5][6] Dual oxidase is an enzyme that was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2 (this enzyme). The protein location is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells[7] and hDUOX2 in the salivary glands and gastrointestinal tract.[8][9][10]

Function

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Investigations into reactive oxygen species (ROS) in biological systems have, until recently, focused on characterization of phagocytic cell processes. It is now well accepted that production of such species is not restricted to phagocytic cells and can occur in eukaryotic non-phagocytic cell types via NADPH oxidase (NOX) or dual oxidase (DUOX). This new family of proteins, termed the NOX/DUOX family or NOX family of NADPH oxidases, consists of homologs to the catalytic moiety of phagocytic NADPH-oxidase, gp91phox. Members of the NOX/DUOX family have been found throughout eukaryotic species, including invertebrates, insects, nematodes, fungi, amoeba, algae, and plants (not found in prokaryotes). These enzymes clearly demonstrate regulated production of ROS as their sole function. Genetic analyses have implicated NOX/DUOX derived ROS in biological roles and pathological conditions including hypertension (NOX1), innate immunity (NOX2/DUOX), otoconia formation in the inner ear (NOX3) and thyroid hormone biosynthesis (DUOX1/2).DUOX2 is the isoform that generates H2O2 utilized by thyroid peroxidase (TPO) for the biosynthesis of thyroid hormones,[11] supported by the discovery of congenital hypothyroidism resultant from an inactivating mutation in the DUOX2 gene.[5][12]

The family currently has seven members including NOX1, NOX2 (formerly known as gp91phox), NOX3, NOX4, NOX5, DUOX1 and DUOX2.

This protein is known as a dual oxidase because it has both a peroxidase homology domain and a gp91phox domain.[13]

Duox are also implicated in lung defence system[14] and especially in cystic fibrosis.[15][16][17]

Schema of duox implication in human lung defence system

Schematic diagram of the respiratory tract antimicrobial defense system.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140279 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000068452 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Dupuy C, Ohayon R, Valent A, Noël-Hudson MS, Dème D, Virion A (December 1999). "Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas". J. Biol. Chem. 274 (52): 37265–9. doi:10.1074/jbc.274.52.37265. PMID 10601291.
  6. ^ De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F (July 2000). of Two Human Thyroid cDNAs Encoding New Members of the NADPH Oxidase Family.pdf "Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family" (PDF). J. Biol. Chem. 275 (30): 23227–33. doi:10.1074/jbc.M000916200. PMID 10806195. S2CID 19424568. {{cite journal}}: Check |url= value (help)
  7. ^ Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, Setiadi H, Wu R (August 2005). "Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium". FEBS Lett. 579 (21): 4911–7. doi:10.1016/j.febslet.2005.08.002. PMID 16111680. S2CID 34266530.
  8. ^ Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL (August 2003). "Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense". FASEB J. 17 (11): 1502–4. doi:10.1096/fj.02-1104fje. PMID 12824283. S2CID 2187431.
  9. ^ El Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D, Ohayon R, Kaniewski J, Noël-Hudson MS, Bidart JM, Schlumberger M, Virion A, Dupuy C (May 2005). "Dual oxidase2 is expressed all along the digestive tract". Am. J. Physiol. Gastrointest. Liver Physiol. 288 (5): G933–42. CiteSeerX 10.1.1.334.1785. doi:10.1152/ajpgi.00198.2004. PMID 15591162.
  10. ^ Rokutan K, Kawahara T, Kuwano Y, Tominaga K, Nishida K, Teshima-Kondo S (July 2008). "Nox enzymes and oxidative stress in the immunopathology of the gastrointestinal tract". Semin Immunopathol. 30 (3): 315–27. doi:10.1007/s00281-008-0124-5. PMID 18521607. S2CID 22923871.
  11. ^ Visser, T. J. (2018). Regulation of Thyroid Function, Synthesis, and Function of Thyroid Hormones. In P. Vitti & L. Hegedüs (Eds.), Thyroid Diseases Pathogenesis, Diagnosis, and Treatment. Springer.
  12. ^ Moreno JC, Bikker H, Kempers MJ, van Trotsenburg AS, Baas F, de Vijlder JJ, Vulsma T, Ris-Stalpers C (July 2002). "Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism". N. Engl. J. Med. 347 (2): 95–102. doi:10.1056/NEJMoa012752. PMID 12110737.
  13. ^ "Entrez Gene: DUOX2 dual oxidase 2".
  14. ^ Fischer H (October 2009). "Mechanisms and function of DUOX in epithelia of the lung". Antioxid. Redox Signal. 11 (10): 2453–65. doi:10.1089/ARS.2009.2558. PMC 2823369. PMID 19358684.
  15. ^ Rada B, Lekstrom K, Damian S, Dupuy C, Leto TL (October 2008). "The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells". J. Immunol. 181 (7): 4883–93. doi:10.4049/jimmunol.181.7.4883. PMC 2776642. PMID 18802092.
  16. ^ Conner GE, Salathe M, Forteza R (December 2002). "Lactoperoxidase and hydrogen peroxide metabolism in the airway". Am. J. Respir. Crit. Care Med. 166 (12 Pt 2): S57–61. doi:10.1164/rccm.2206018. PMID 12471090.
  17. ^ Rada B, Leto TL (2008). "Oxidative innate immune defenses by Nox/Duox family NADPH oxidases". Trends in Innate Immunity. Contributions to Microbiology. Vol. 15. pp. 164–87. doi:10.1159/000136357. ISBN 978-3-8055-8548-4. PMC 2776633. PMID 18511861. {{cite book}}: |journal= ignored (help)

Further reading

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