Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T29741
(Former ID: TTDI02136)
|
|||||
Target Name |
NADPH oxidase 4 (NOX4)
|
|||||
Synonyms |
Renal NAD(P)Hoxidase; Renal NAD(P)H-oxidase; RENOX; Kidney superoxideproducing NADPH oxidase; Kidney superoxide-producing NADPH oxidase; Kidney oxidase1; Kidney oxidase-1; KOX1; KOX-1
Click to Show/Hide
|
|||||
Gene Name |
NOX4
|
|||||
Target Type |
Clinical trial target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Fibrosis [ICD-11: GA14-GC01] | |||||
Function |
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 5 and isoform 6 display reduced activity. Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox.
Click to Show/Hide
|
|||||
BioChemical Class |
NADH/NADPH oxidoreductase
|
|||||
UniProt ID | ||||||
EC Number |
EC 1.6.3.-
|
|||||
Sequence |
MAVSWRSWLANEGVKHLCLFIWLSMNVLLFWKTFLLYNQGPEYHYLHQMLGLGLCLSRAS
ASVLNLNCSLILLPMCRTLLAYLRGSQKVPSRRTRRLLDKSRTFHITCGVTICIFSGVHV AAHLVNALNFSVNYSEDFVELNAARYRDEDPRKLLFTTVPGLTGVCMVVVLFLMITASTY AIRVSNYDIFWYTHNLFFVFYMLLTLHVSGGLLKYQTNLDTHPPGCISLNRTSSQNISLP EYFSEHFHEPFPEGFSKPAEFTQHKFVKICMEEPRFQANFPQTWLWISGPLCLYCAERLY RYIRSNKPVTIISVMSHPSDVMEIRMVKENFKARPGQYITLHCPSVSALENHPFTLTMCP TETKATFGVHLKIVGDWTERFRDLLLPPSSQDSEILPFIQSRNYPKLYIDGPFGSPFEES LNYEVSLCVAGGIGVTPFASILNTLLDDWKPYKLRRLYFIWVCRDIQSFRWFADLLCMLH NKFWQENRPDYVNIQLYLSQTDGIQKIIGEKYHALNSRLFIGRPRWKLLFDEIAKYNRGK TVGVFCCGPNSLSKTLHKLSNQNNSYGTRFEYNKESFS Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T80OPZ |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | GKT-137831 | Drug Info | Phase 2 | Fibrosis | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | GKT-137831 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
---|---|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
|
There is no similarity protein (E value < 0.005) for this target
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 6.65E-05 |
---|---|---|---|---|---|
Closeness centrality | 2.10E-01 | Radiality | 1.37E+01 | Clustering coefficient | 2.00E-01 |
Neighborhood connectivity | 2.16E+01 | Topological coefficient | 2.30E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
---|---|
Target Poor or Non Binders | Top | |||||
---|---|---|---|---|---|---|
Target Poor or Non Binders |
Target Regulators | Top | |||||
---|---|---|---|---|---|---|
Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | TGF_beta_Receptor Signaling Pathway | |||||
2 | TSH Signaling Pathway | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Thyroid hormone synthesis | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Signaling events mediated by PTP1B | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Oxidative Stress | |||||
2 | Spinal Cord Injury |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Nicotinamide Adenine Dinucleotide Phosphate Oxidase (NOX) in Experimental Liver Fibrosis: GKT137831 as a Novel Potential Therapeutic Agent. Hepatology. 2012 December; 56(6): 2316-2327. | |||||
REF 2 | ClinicalTrials.gov (NCT02010242) Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria. U.S. National Institutes of Health. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.