NOX4: 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. 7 isoforms of the human protein are produced by alternative splicing.
Protein type: Membrane protein, multi-pass; Nucleolus; EC 1.6.3.-; Membrane protein, integral; Oxidoreductase; Cell cycle regulation
Chromosomal Location of Human Ortholog: 11q14.2-q21
Cellular Component: endoplasmic reticulum membrane; focal adhesion; mitochondrion; perinuclear region of cytoplasm; apical plasma membrane; nucleolus; stress fiber; integral to membrane; NADPH oxidase complex
Molecular Function: FAD binding; electron carrier activity; oxygen sensor activity; NAD(P)H oxidase activity; superoxide-generating NADPH oxidase activity; nucleotide binding; heme binding
Biological Process: positive regulation of apoptosis; cell morphogenesis; cell aging; homocysteine metabolic process; positive regulation of smooth muscle cell migration; cardiac muscle cell differentiation; positive regulation of protein kinase B signaling cascade; positive regulation of MAP kinase activity; negative regulation of cell proliferation; positive regulation of stress fiber formation; response to hypoxia; inflammatory response; superoxide release; bone resorption
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