Human Gene NOX4 (ENST00000263317.9) from GENCODE V44
Description: Homo sapiens NADPH oxidase 4 (NOX4), transcript variant 1, mRNA. (from RefSeq NM_016931) RefSeq Summary (NM_016931): 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]. Gencode Transcript: ENST00000263317.9 Gencode Gene: ENSG00000086991.13 Transcript (Including UTRs) Position: hg38 chr11:89,324,353-89,491,375 Size: 167,023 Total Exon Count: 18 Strand: - Coding Region Position: hg38 chr11:89,326,756-89,491,246 Size: 164,491 Coding Exon Count: 18
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.
Pfam Domains: PF08022 - FAD-binding domain PF01794 - Ferric reductase like transmembrane component PF08030 - Ferric reductase NAD binding domain
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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