This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009],
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Function:
developmental stage:Expressed in fetal kidney and fetal liver.,enzyme regulation:Inhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium.,Function:Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. Isoform 3 is not functional. Isoform 4 displays an increased activity while isoform 5 and isoform 6 display reduced activity. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation.,induction:By 7-ketocholesterol (at protein level).,PTM:Isoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function.,similarity:Contains 1 FAD-binding FR-type domain.,similarity:Contains 1 ferric oxidoreductase domain.,subcellular location:May localize to plasma membrane and focal adhesions. May also localize to the nucleus (PubMed:15927447).,subunit:Interacts with protein disulfide isomerase (By similarity). Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4.,tissue specificity:Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells.,
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Cellular Localization:
Endoplasmic reticulum membrane ; Multi-pass membrane protein. Cell membrane ; Multi-pass membrane protein . Cell junction, focal adhesion . May localize to plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus.; [Isoform 4]: Nucleus . Nucleus, nucleolus .
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Tissue Expression:
Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells.
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Research Areas:
>>AGE-RAGE signaling pathway in diabetic complications ;
>>Alcoholic liver disease ;
>>Alzheimer disease ;
>>Pathways of neurodegeneration - multiple diseases ;
>>Chemical carcinogenesis - reactive oxygen species