NADPH oxidase 4; kidney oxidase-1; KOX-1; kidney superoxide-producing NADPH oxidase; renal NADPH-oxidase (NOX4, RENOX)
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Function
- constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox
- regulates signaling cascades via phosphatase inhibition
- oxygen sensor regulating the KCNK3/TASK-1 K+ channel & HIF1A activity (putative)
- regulation of insulin signaling cascade role in apoptosis, bone resorption & lipolysaccharide-mediated activation of NFKB
- may produce superoxide in the nucleus & play a role in regulating gene expression upon cell stimulation
- interacts with protein disulfide isomerase
- interacts with, relocalizes & stabilizes CYBA/p22phox
- interacts with TLR4, residues 248-575
- contains 1 ferric oxidoreductase domain, residues 58-561
- inhibited by plumbagin, diphenylene iodonium
- activated by phorbol 12-myristate 13-acetate, insulin
Structure
- contains 1 FAD-binding FR-type domain
- contains 1 ferric oxidoreductase domain
Compartment
- endoplasmic reticulum
- cell junction, focal adhesion (probable).
- nucleus (probable)
Alternative splicing
named isoforms=7 isoform 3 is not functional; isoform 4 displays an increased activity; isoform 3 & isoform 4 are N-glycosylated; isoform 4 glycosylation required for function; isoform 5 & isoform 6 display reduced activity;
Expression
- expressed by distal tubular cells in kidney cortex & in endothelial cells
- widely expressed
- expressed in kidney > heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, airway epithelial cells
- expressed in fetal kidney & fetal liver
- induced by 7-ketocholesterol
Pathology
- expressed in several brain tumor cell lines