ID:NOX4_HUMAN DESCRIPTION: RecName: Full=NADPH oxidase 4; EC=1.6.3.-; AltName: Full=Kidney oxidase-1; Short=KOX-1; AltName: Full=Kidney superoxide-producing NADPH oxidase; AltName: Full=Renal NAD(P)H-oxidase; 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. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 4 displays an increased activity. Isoform 5 and isoform 6 display reduced activity. ENZYME REGULATION: Inhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium. SUBUNIT: Interacts with protein disulfide isomerase (By similarity). Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein (Probable). Cell junction, focal adhesion (Probable). Nucleus (Probable). Note=May localize to plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus. 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. DEVELOPMENTAL STAGE: Expressed in fetal kidney and fetal liver. 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.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NPH5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000902 cell morphogenesis GO:0001666 response to hypoxia GO:0006801 superoxide metabolic process GO:0006954 inflammatory response GO:0007568 aging GO:0007569 cell aging GO:0008285 negative regulation of cell proliferation GO:0010467 gene expression GO:0014911 positive regulation of smooth muscle cell migration GO:0022900 electron transport chain GO:0034599 cellular response to oxidative stress GO:0042554 superoxide anion generation GO:0043065 positive regulation of apoptotic process GO:0043406 positive regulation of MAP kinase activity GO:0045453 bone resorption GO:0050667 homocysteine metabolic process GO:0051496 positive regulation of stress fiber assembly GO:0051897 positive regulation of protein kinase B signaling GO:0055007 cardiac muscle cell differentiation GO:0055114 oxidation-reduction process GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071320 cellular response to cAMP GO:0071333 cellular response to glucose stimulus GO:0071480 cellular response to gamma radiation GO:0071560 cellular response to transforming growth factor beta stimulus GO:0072593 reactive oxygen species metabolic process GO:2000379 positive regulation of reactive oxygen species metabolic process GO:2000573 positive regulation of DNA biosynthetic process
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
