The Duox and Nox5 Subfamilies of NADPH-Oxidases


In addition to a C-terminal gp91phox-homology domain, a large splice form of Nox5 and Duox have additional predicted protein domains. All have a calcium-binding domain containing 2 EF-hand calcium-binding motifs. In addition, the Duox enzymes have an N-terminal region that is shows homology with known peroxidases including myeloperoxidase, thyroid peroxidase, lactoperoxidase and others. A family tree constructed by comparing the sequences of the Duox family tree with those of other known peroxidases demonstrates a relationship with ovoperoxidases from sea urchin.


The transmembrane topology of Duox predicts that ROS generated by the gp91phox homology domain will serve as one of the substrates for the peroxidase domain. Localization of Duox at the plasma membrane allows the enzyme to oxidize extracellular proteins and/or small molecules. In the case of C. elegans Duox, the enzyme catalyzes the cross-linking of extracellular cuticle proteins, cross-linking them to stabilize the structure. Similar functions are proposed for mammalian Duox1 and Duox2.

 

 

 

In addition to a C-terminal gp91phox-homology domain, a large splice form of Nox5 and Duox have additional predicted protein domains. All have a calcium-binding domain containing 2 EF-hand calcium-binding motifs. In addition, the Duox enzymes have an N-terminal region that is shows homology with known peroxidases including myeloperoxidase, thyroid peroxidase, lactoperoxidase and others

 

 

 

 

 

 

The Duox enzymes have an N-terminal region that is shows homology with known peroxidases including myeloperoxidase, thyroid peroxidase, lactoperoxidase and others.

 

 

 

 

A family tree constructed by comparing the sequences of the Duox family tree with those of other known peroxidases demonstrates a relationship with ovoperoxidases from sea urchin.