NOX2

The CYBB gene encode cytochrome b-245, beta chain. This protein is subunit of a group of proteins that forms an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Within this complex, the cytochrome b-245, beta chain has an alpha chain partner (produced from the CYBA gene). Both alpha and beta chains are required for either to function and the NADPH oxidase complex requires both chains in order to be functional. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Nox2 is the catalytic, membrane-bound subunit of NADPH oxidase. It is inactive until it binds to the membrane-anchored p22phox, forming the heterodimer known as flavocytochrome b558. After activation, the regulatory subunits p67phox, p47phox, p40phox and a GTPase, typically Rac, are recruited to the complex to form NADPH oxidase on the plasma membrane or phagosomal membrane. Nox2 itself is composed of an N-terminal transmembrane domain that binds two heme groups, and a C-terminal domain that is able to bind to FAD and NADPH. Evidence has shown that it plays an important role in atherosclerotic lesion development in the aortic arch, thoracic, and abdominal aorta. It has also been shown to play a part in determining the size of a myocardial infarction due to its connection to ROS, which play a role in myocardial reperfusion injury. This was a result of the relation between Nox2 and signaling necessary for neutrophil recruitment. Furthermore, it increases global post-reperfusion oxidative stress, likely due to decreased STAT3 and Erk phosphorylation. Endothelial Nox2 limits NF-κB activation and TLR4 expression, which in turn attenuates the severity of hypotension and systemic inflammation induced by lipopolysaccharides (LPS). It seems that Nox2 also plays an important role in angiotensin II-mediated inward remodelling in cerebral arterioles due to the emittance of superoxides from Nox2-containing NADPH oxidases. == Clinical significance ==

CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). CGD is characterized by recurrent, severe infections to pathogens that are normally harmless to humans, such as the common mold Aspergillus niger, and can result from point mutations in the gene encoding Nox2. Since Nox2 was shown to play an essential role in determining the size of a myocardial infarction, the protein can be a potential target for drug medication due to its negative effect on myocardial reperfusion. Lastly, targeting Nox2 in the bone marrow could be a great therapeutic attempt at treating vascular injury during diabetic retinopathy (damage to the retina), because the Nox2-generated ROS which are produced by the bone-marrow derived cells & local retinal cells are accumulating the vascular injury in the diabetic retina area. CYBB transcript levels are upregulated in the lung parenchyma of smokers. == Interactions ==

Nox2 has been shown to interact directly with podocyte TRPC6 channels. == References ==