HCSGD entry for NOX4
1. General information
| Official gene symbol | NOX4 |
|---|---|
| Entrez ID | 50507 |
| Gene full name | NADPH oxidase 4 |
| Other gene symbols | KOX KOX-1 RENOX |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
This gene isn't in PPI subnetwork.
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000166 | Nucleotide binding | TAS | molecular_function |
| GO:0000902 | Cell morphogenesis | IEA ISS | biological_process |
| GO:0001666 | Response to hypoxia | IEA | biological_process |
| GO:0005634 | Nucleus | IEA | cellular_component |
| GO:0005739 | Mitochondrion | IEA | cellular_component |
| GO:0005789 | Endoplasmic reticulum membrane | IEA | cellular_component |
| GO:0005925 | Focal adhesion | IEA | cellular_component |
| GO:0006954 | Inflammatory response | TAS | biological_process |
| GO:0007569 | Cell aging | IEA ISS | biological_process |
| GO:0008285 | Negative regulation of cell proliferation | IEA ISS | biological_process |
| GO:0009055 | Electron carrier activity | TAS | molecular_function |
| GO:0014911 | Positive regulation of smooth muscle cell migration | IEA | biological_process |
| GO:0016021 | Integral component of membrane | IEA TAS | cellular_component |
| GO:0016174 | NAD(P)H oxidase activity | IEA TAS | molecular_function |
| GO:0016175 | Superoxide-generating NADPH oxidase activity | IEA | molecular_function |
| GO:0016324 | Apical plasma membrane | IEA | cellular_component |
| GO:0016491 | Oxidoreductase activity | IEA | molecular_function |
| GO:0019826 | Oxygen sensor activity | TAS | molecular_function |
| GO:0020037 | Heme binding | TAS | molecular_function |
| GO:0035051 | Cardiocyte differentiation | IEA | biological_process |
| GO:0042554 | Superoxide anion generation | IEA ISS | biological_process |
| GO:0043020 | NADPH oxidase complex | IEA | cellular_component |
| GO:0043065 | Positive regulation of apoptotic process | IEA | biological_process |
| GO:0043406 | Positive regulation of MAP kinase activity | IEA | biological_process |
| GO:0045453 | Bone resorption | IEA | biological_process |
| GO:0048471 | Perinuclear region of cytoplasm | IEA | cellular_component |
| GO:0050660 | Flavin adenine dinucleotide binding | TAS | molecular_function |
| GO:0050667 | Homocysteine metabolic process | IDA | biological_process |
| GO:0051496 | Positive regulation of stress fiber assembly | IEA | biological_process |
| GO:0051897 | Positive regulation of protein kinase B signaling | IEA | biological_process |
| GO:0055114 | Oxidation-reduction process | IDA | biological_process |
| GO:0070374 | Positive regulation of ERK1 and ERK2 cascade | IEA | biological_process |
| GO:0071320 | Cellular response to cAMP | IEA | biological_process |
| GO:0071333 | Cellular response to glucose stimulus | IEA | biological_process |
| GO:0071480 | Cellular response to gamma radiation | IEA | biological_process |
| GO:0071560 | Cellular response to transforming growth factor beta stimulus | IEA | biological_process |
| GO:0072341 | Modified amino acid binding | IDA | molecular_function |
| GO:0072593 | Reactive oxygen species metabolic process | IDA | biological_process |
| GO:2000379 | Positive regulation of reactive oxygen species metabolic process | IEA | biological_process |
| GO:2000573 | Positive regulation of DNA biosynthetic process | IEA | biological_process |
Entries Per Page
Displaying Page of
4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0806632537 | 0.1239720451 | 0.5984040304 | 0.6771825970 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.7626372242 |
| GSE13712_SHEAR | Down | -1.6308329959 |
| GSE13712_STATIC | Down | -0.8437829068 |
| GSE19018 | Down | -0.0777373891 |
| GSE19899_A1 | Up | 0.2501041790 |
| GSE19899_A2 | Up | 0.0091396670 |
| PubMed_21979375_A1 | Up | 0.1790445093 |
| PubMed_21979375_A2 | Down | -0.1127910945 |
| GSE35957 | Up | 0.0563148670 |
| GSE36640 | Down | -0.1053074329 |
| GSE54402 | Up | 1.3570038240 |
| GSE9593 | Down | -0.0496816090 |
| GSE43922 | Up | 0.4455727180 |
| GSE24585 | Up | 0.4877893791 |
| GSE37065 | Up | 0.3499716762 |
| GSE28863_A1 | Up | 0.2615190344 |
| GSE28863_A2 | Up | 0.2722028091 |
| GSE28863_A3 | Down | -0.0994200094 |
| GSE28863_A4 | Down | -0.0620868949 |
| GSE48662 | Up | 0.3844422607 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-148b-3p | MIMAT0000759 | MIRT019477 | Microarray | Functional MTI (Weak) | 17612493 |
Entries Per Page
Displaying Page of
- mirRecord
No target information from mirRecord
- mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 17 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27057461 | IFNgamma is capable of inducing expression of constitutively active NADPH oxidase NOX4 in tumor cells leading to generation of reactive oxygen species (ROS) damaging DNA, activation of DNA damage response and cell cycle arrest/premature cellular senescence |
| 25982278 | IFNgamma induces oxidative stress, DNA damage and tumor cell senescence via TGFbeta/SMAD signaling-dependent induction of Nox4 and suppression of ANT2 |
| 25982278 | Using human and mouse normal and cancer cell models, we now show that TNFalpha and IFNgamma induce NADPH oxidases Nox4 and Nox1, reactive oxygen species (ROS), DDR signaling and premature senescence |
| 25982278 | Unlike mouse tumor cells that required concomitant presence of IFNgamma and TNFalpha, short exposure to IFNgamma alone was sufficient to induce Nox4, Nox1 and DDR in human cells |
| 25982278 | The expression of Nox4/Nox1 required Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling and the effect was mediated by downstream activation of transforming growth factor-beta (TGFbeta) secretion and consequent autocrine/paracrine activation of the TGFbeta/Smad pathway |
| 25982278 | In contrast to mouse B16 cells, inability of TC-1 cells to respond to IFNgamma/TNFalpha by DDR and senescence correlated with the lack of TGFbeta and Nox4 response, supporting the role of ROS induced by NADPH oxidases in cytokine-induced senescence |
| 25526894 | Epigenetic mechanisms regulate NADPH oxidase-4 expression in cellular senescence |
| 25526894 | Recent studies implicate the reactive oxygen species (ROS)-generating enzyme, NADPH oxidase 4 (Nox4) in cellular senescence |
| 25526894 | In this study, we investigated potential mechanisms for epigenetic regulation of Nox4 |
| 25526894 | We observed constitutively high levels of Nox4 gene/protein and activity in a model of replication-induced cellular senescence of lung fibroblasts |
| 25526894 | In replicative senescent fibroblasts, the Nox4 gene is enriched with the activation histone mark, H4K16Ac, and inversely associated with the repressive histone mark, H4K20Me3, supporting an active transcriptional chromatin conformation |
| 25526894 | The Nox4 gene promoter is rich in CpG sites; mixed copies of methylated and unmethylated Nox4 DNA were detected in both nonsenescent and senescent cells |
| 25526894 | Interestingly, the Nox4 gene is variably associated with specific DNA methyltransferases and methyl binding proteins in these two cell populations |
| 25526894 | These results indicate a critical role for histone modifications involving H4K16Ac in epigenetic activation of the Nox4 gene, while the role of DNA methylation may be contextual |
| 25526894 | Defining mechanisms for the epigenetic regulation of Nox4 will aid in the development of novel therapeutic strategies for age-related diseases in which this gene is overexpressed, in particular idiopathic pulmonary fibrosis and cancer |
| 25311168 | Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples |
| 25311168 | Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD |
| 25033544 | NADPH oxidase NOX4 is a source of reactive oxygen species in many tissue of human body |
| 25033544 | NOX4 products of activity are connected with various processes that take on the cellular and tissue level |
| 25033544 | On the other hand NOX4 also stimulates to proliferation various types of cancer and primary cells, what promotes pathologies |
| 25033544 | NOX4 participates in epithelial-mesenchymal transition, important for tumor cells invasion and metastasis |
| 25033544 | Many research concern the role of NOX4 in the physiology and pathology of the cardiovascular system |
| 25033544 | It was shown that NOX4 has an impact on vasoconstriction, atherosclerosis development, vascular cells hypertrophy, apoptosis and differentiation |
| 25033544 | NOX4 plays both positive and negative role in the organism |
| 25033544 | Better understanding of NOX4 regulation and its involvement in signaling pathways give a hope to control the development of many diseases |
| 24727683 | We recently reported that indoxyl sulfate (IS), a uremic toxin, directly activates aryl hydrocarbon receptor (AhR) and generates oxidative stress through NADPH oxidase-4 in human umbilical vein endothelial cells (HUVECs) |
| 24583638 | Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents |
| 23662809 | Evidence for novel aspects of Nox4 oxidase regulation of mitochondrial function and peroxide generation in an endothelial cell model of senescence |
| 23662809 | Cellular aging appears to promote a Nox4 interaction with mitochondria that disrupts complex I in the electron transport chain and increases the detection of mitochondrial H(2)O(2) |
| 23662809 | Nox4 appears to maintain a highly interconnected mitochondrial network, which may influence mitochondrial fission and/or fusion mechanisms in a manner that could be a contributing factor in the loss of replicative lifespan seen in senescence |
| 23514110 | Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4 |
| 23514110 | Nox4 (NADPH oxidase 4) induces cellular senescence in human endothelial cells; however, intracellular targets for Nox4 remained elusive |
| 23514110 | In the present study, we show that Nox4 induces mitochondrial dysfunction in human endothelial cells |
| 23514110 | Nox4 depletion induced alterations in mitochondrial morphology, stabilized mitochondrial membrane potential and decreased production of H(2)O(2) in mitochondria |
| 23514110 | High-resolution respirometry in permeabilized cells combined with native PAGE demonstrated that Nox4 specifically inhibits the activity of mitochondrial electron transport chain complex I, and this was associated with a decreased concentration of complex I subunits |
| 23514110 | These data suggest a new pathway by which sustained Nox4 activity decreases mitochondrial function |
| 23385065 | Furthermore, the observed IL1- and TGFbeta-induced expression of NAPDH oxidase Nox4 indicates a mechanistic link between the senescence-associated secretory phenotype (SASP) and DNA damage signaling as a feature shared by development of all major forms of paracrine bystander senescence |
| 23216904 | ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic Ras-induced premature senescence |
| 23216904 | Here, we show that through the Ras/MEK pathway, Ras oncogene up-regulated the expression of superoxide-generating oxidases, Nox1 in rat REF52 cells and Nox4 in primary human lung TIG-3 cells, leading to an increase in intracellular level of ROS |
| 23216904 | Ablation of Nox1 and Nox4 by small interfering RNAs (siRNAs) blocked the RasV12 senescent phenotype including beta-galactosidase activity, growth arrest and accumulation of tumor suppressors such as p53 and p16Ink4a |
| 23216904 | Furthermore, Nox1 and Nox4 siRNAs inhibited both Ras-induced DNA damage response and p38MAPK activation, whereas overexpression of Nox1 and Nox4 alone was able to induce senescence |
| 21841319 | NOX2 and NOX4 were correlated with the late and slow phase and contributed greatly to EPCs senescence |
| 21511256 | In young human umbilical vein endothelial cells, this miR is involved in a premature senescence-like phenotype through direct targeting of the NOX4 protein, implicated in cell senescence and aging |
| 20523116 | NADPH oxidase 4 is an oncoprotein localized to mitochondria |
| 20523116 | We found that NOX4 was overexpressed in the majority of breast cancer cell lines and primary breast tumors |
| 20523116 | NOX4 was also overexpressed in ovarian tumors |
| 20523116 | Overexpression of NOX4 in normal breast epithelial cells resulted in cellular senescence, resistance to apoptosis, and tumorigenic transformation |
| 20523116 | Overexpression of NOX4 in already transformed breast tumor cells also showed increased tumorigenicity |
| 20523116 | Strong evidence suggests that regulation of these processes occurs through NOX4 generation of ROS in the mitochondria |
| 20523116 | We demonstrate that the NOX4 protein contains a 73 amino acid long mitochondrial localization signal at the N-terminus that is capable of transporting a passenger protein GFP into the mitochondria |
| 20523116 | Together, this study provides evidence for an oncogenic function for NOX4 protein localized to mitochondria and suggests that NOX4 is a novel source of ROS produced in the mitochondria |
| 19681754 | The NADPH oxidase Nox4 restricts the replicative lifespan of human endothelial cells |
| 19681754 | In HUVECs (human umbilical vein endothelial cells), Nox4 is predominantly expressed, but its role in replicative senescence of HUVECs remains to be elucidated |
| 19681754 | Using shRNA (small-hairpin RNA)-mediated knockdown of Nox4, implicating lentiviral vectors, we addressed the question of whether lifelong depletion of Nox4 in HUVECs would influence the senescent phenotype |
| 19681754 | We found a significant extension of the replicative lifespan of HUVECs upon knockdown of Nox4 |
| 19681754 | Nox4 depletion had no discernable influence on the activity of MAPKs and stress-activated kinases, but reduced the degree of oxidative DNA damage |
| 19681754 | These results suggest that Nox4 activity increases oxidative damage in HUVECs, leading to loss of replicative potential, which is at least partly independent of telomere attrition |
| 16324151 | The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells |
| 16324151 | The superoxide-producing NAD(P)H oxidase Nox4 was initially identified as an enzyme that is highly expressed in the kidney and is possibly involved in oxygen sensing and cellular senescence |
| 16324151 | Here we show that Nox4 preferentially localizes to the nucleus of human umbilical vein endothelial cells (HUVECs), by immunocytochemistry and immunoelectron microscopy using three kinds of affinity-purified antibodies raised against distinct immunogens from human Nox4 |
| 16324151 | Silencing of Nox4 by RNA interference (RNAi) abrogates nuclear signals given with the antibodies, confirming the nuclear localization of Nox4 |
| 16324151 | The nuclear fraction of HUVECs exhibits an NAD(P)H-dependent superoxide-producing activity in a manner dependent on Nox4, which activity can be enhanced upon cell stimulation with phorbol 12-myristate 13-acetate |
| 16324151 | Both basal and stimulated transcriptional activities are impaired by RNAi-mediated Nox4 silencing |
| 16324151 | Thus Nox4 appears to produce superoxide in the nucleus of HUVECs, thereby regulating gene expression via a mechanism for oxidative stress response |
| 10869423 | Renox is homologous to gp91(phox) (91-kDa subunit of the phagocyte oxidase), the electron-transporting subunit of phagocytic NADPH oxidase, and contains all of the structural motifs considered essential for binding of heme, flavin, and nucleotide |
| 10869423 | NIH 3T3 fibroblasts overexpressing transfected Renox show increased production of superoxide and develop signs of cellular senescence |
| 10869423 | Our data suggest that Renox, as a renal source of reactive oxygen species, is a likely candidate for the oxygen sensor function regulating oxygen-dependent gene expression and may also have a role in the development of inflammatory processes in the kidney |
Entries Per Page
Displaying Page of
