DUOX2
Encyclopedia
Dual oxidase 2, also known as DUOX2 or ThOX2 (for thyroid oxidase) is an enzyme
which in humans is encoded by the DUOX2 gene
. 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 and hDUOX2 in the salivary glands and gastrointestinal tract.
) 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, alga, 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). It has been suggested that DUOX2 is the isoform to generate H2O2
utilized by thyroid peroxidase
(TPO) for the biosynthesis of thyroid hormone
s, supported by the discovery of congenital hypothyroidism resultant from an inactivating mutation in the DUOX2 gene.
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.
Duox are also implicated in lung defence system and especially in cystic fibrosis
.
Schema of duox implication in human lung
defence system
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
which in humans is encoded by the DUOX2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. 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 and hDUOX2 in the salivary glands and gastrointestinal tract.
Function
Investigations into reactive oxygen species (ROSReactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
) 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
NADPH oxidase
The NADPH oxidase is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.-Subunits:It is made up of six subunits...
(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
CYBB
Cytochrome b-245, beta polypeptide -- also known as CYBB, P91-PHOX, and NOX2-- is a human gene encoding a glycoprotein.-External links:...
. Members of the NOX/DUOX family have been found throughout eukaryotic species, including invertebrates, insects, nematodes, fungi, amoeba, alga, 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
NOX1
NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.-Further reading:...
) , innate immunity (NOX2
CYBB
Cytochrome b-245, beta polypeptide -- also known as CYBB, P91-PHOX, and NOX2-- is a human gene encoding a glycoprotein.-External links:...
/DUOX), otoconia formation in the inner ear (NOX3
NOX3
NADPH oxidase 3 is an enzyme that in humans is encoded by the NOX3 gene.-Further reading:...
) and thyroid hormone biosynthesis (DUOX1/2). It has been suggested that DUOX2 is the isoform to generate H2O2
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
utilized by thyroid peroxidase
Thyroid peroxidase
Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...
(TPO) for the biosynthesis of thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s, supported by the discovery of congenital hypothyroidism resultant from an inactivating mutation in the DUOX2 gene.
The family currently has seven members including NOX1
NOX1
NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.-Further reading:...
, NOX2
CYBB
Cytochrome b-245, beta polypeptide -- also known as CYBB, P91-PHOX, and NOX2-- is a human gene encoding a glycoprotein.-External links:...
(formerly known as gp91phox), NOX3
NOX3
NADPH oxidase 3 is an enzyme that in humans is encoded by the NOX3 gene.-Further reading:...
, NOX4
NOX4
NADPH oxidase 4 is an enzyme that in humans is encoded by the NOX4 gene.-Further reading:...
, NOX5
NOX5
NADPH oxidase, EF-hand calcium binding domain 5, also known as NOX5, is a protein which in humans is encoded by the NOX5 gene.- Function :NOX5 is a novel NADPH oxidase that generates superoxide....
, DUOX1
DUOX1
Dual oxidase 1, also known as DUOX1 or ThOX1 , is an enzyme which in humans is encoded by the DUOX1 gene. DUOX1 was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2...
and DUOX2.
This protein is known as a dual oxidase because it has both a peroxidase homology domain and a gp91phox domain.
Duox are also implicated in lung defence system and especially in cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
.
Schema of duox implication in human lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
defence system