Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0FFJH8)

DOT Name NADPH oxidase 3 (NOX3)
Synonyms EC 1.6.3.-; Mitogenic oxidase 2; MOX-2; gp91phox homolog 3; GP91-3
Gene Name NOX3
Related Disease
Diabetic retinopathy ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Cardiomyopathy ( )
Chronic granulomatous disease ( )
Congestive heart failure ( )
Diabetic kidney disease ( )
Granulomatous disease, chronic, X-linked ( )
High blood pressure ( )
Pathologic nystagmus ( )
Prostate cancer ( )
Prostate neoplasm ( )
Psoriatic arthritis ( )
Autoimmune disease ( )
Hyperinsulinemia ( )
Obesity ( )
Relapsing-remitting multiple sclerosis ( )
Agranulocytosis ( )
Graves disease ( )
UniProt ID
NOX3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
1.6.3.-
Pfam ID
PF08022 ; PF01794 ; PF08030
Sequence
MMGCWILNEGLSTILVLSWLGINFYLFIDTFYWYEEEESFHYTRVILGSTLAWARASALC
LNFNCMLILIPVSRNLISFIRGTSICCRGPWRRQLDKNLRFHKLVAYGIAVNATIHIVAH
FFNLERYHWSQSEEAQGLLAALSKLGNTPNESYLNPVRTFPTNTTTELLRTIAGVTGLVI
SLALVLIMTSSTEFIRQASYELFWYTHHVFIVFFLSLAIHGTGRIVRGQTQDSLSLHNIT
FCRDRYAEWQTVAQCPVPQFSGKEPSAWKWILGPVVLYACERIIRFWRFQQEVVITKVVS
HPSGVLELHMKKRGFKMAPGQYILVQCPAISSLEWHPFTLTSAPQEDFFSVHIRAAGDWT
AALLEAFGAEGQALQEPWSLPRLAVDGPFGTALTDVFHYPVCVCVAAGIGVTPFAALLKS
IWYKCSEAQTPLKLSKVYFYWICRDARAFEWFADLLLSLETRMSEQGKTHFLSYHIFLTG
WDENQALHIALHWDENTDVITGLKQKTFYGRPNWNNEFKQIAYNHPSSSIGVFFCGPKAL
SRTLQKMCHLYSSADPRGVHFYYNKESF
Function
NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor, upon formation of a complex with CYBA/p22phox. Plays a role in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
RAC3 GTPase cycle (R-HSA-9013423 )
RHO GTPases Activate NADPH Oxidases (R-HSA-5668599 )

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Diabetic retinopathy DISHGUJM Definitive Altered Expression [1]
Breast cancer DIS7DPX1 Strong Altered Expression [2]
Breast carcinoma DIS2UE88 Strong Altered Expression [2]
Cardiac failure DISDC067 Strong Altered Expression [3]
Cardiomyopathy DISUPZRG Strong Biomarker [3]
Chronic granulomatous disease DIS9ZR24 Strong Biomarker [4]
Congestive heart failure DIS32MEA Strong Altered Expression [3]
Diabetic kidney disease DISJMWEY Strong Biomarker [5]
Granulomatous disease, chronic, X-linked DISNTTS3 Strong Genetic Variation [6]
High blood pressure DISY2OHH Strong Genetic Variation [7]
Pathologic nystagmus DIS1QSPO Strong Biomarker [8]
Prostate cancer DISF190Y Strong Biomarker [9]
Prostate neoplasm DISHDKGQ Strong Biomarker [9]
Psoriatic arthritis DISLWTG2 Strong Altered Expression [10]
Autoimmune disease DISORMTM moderate Genetic Variation [11]
Hyperinsulinemia DISIDWT6 moderate Biomarker [12]
Obesity DIS47Y1K moderate Biomarker [12]
Relapsing-remitting multiple sclerosis DISSXFCF moderate Genetic Variation [11]
Agranulocytosis DISJS4LS Disputed Genetic Variation [13]
Graves disease DISU4KOQ Disputed Genetic Variation [13]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of NADPH oxidase 3 (NOX3). [14]
Progesterone DMUY35B Approved Progesterone decreases the expression of NADPH oxidase 3 (NOX3). [15]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of NADPH oxidase 3 (NOX3). [16]
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References

1 GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.Int J Med Sci. 2017 Sep 19;14(12):1203-1212. doi: 10.7150/ijms.20962. eCollection 2017.
2 The PI3K/Akt/GSK-3/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility.Cancer Biol Med. 2019 Feb;16(1):38-54. doi: 10.20892/j.issn.2095-3941.2018.0253.
3 Increase of NADPH oxidase 3 in heart failure of hereditary cardiomyopathy (1).Can J Physiol Pharmacol. 2019 Sep;97(9):902-908. doi: 10.1139/cjpp-2019-0055. Epub 2019 Mar 21.
4 CYBA encoding p22(phox), the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology.Gene. 2016 Jul 15;586(1):27-35. doi: 10.1016/j.gene.2016.03.050. Epub 2016 Apr 2.
5 A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes.Am J Kidney Dis. 2007 Mar;49(3):394-400. doi: 10.1053/j.ajkd.2006.12.011.
6 NOX4 is the main NADPH oxidase involved in the early stages of hematopoietic differentiation from human induced pluripotent stem cells.Free Radic Biol Med. 2020 Jan;146:107-118. doi: 10.1016/j.freeradbiomed.2019.10.005. Epub 2019 Oct 15.
7 Genome-wide association study identifies loci and candidate genes for non-idiopathic pulmonary hypertensionin Eastern Chinese Han population.BMC Pulm Med. 2018 Oct 5;18(1):158. doi: 10.1186/s12890-018-0719-0.
8 Mouse Magnetic-field Nystagmus in Strong Static Magnetic Fields Is Dependent on the Presence of Nox3.Otol Neurotol. 2018 Dec;39(10):e1150-e1159. doi: 10.1097/MAO.0000000000002024.
9 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
10 Pterostilbene reverses palmitic acid mediated insulin resistance in HepG2 cells by reducing oxidative stress and triglyceride accumulation.Free Radic Res. 2019 Jul;53(7):815-827. doi: 10.1080/10715762.2019.1635252. Epub 2019 Jul 10.
11 Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes.Nat Commun. 2019 Jul 12;10(1):3081. doi: 10.1038/s41467-019-11139-3.
12 Pancreastatin inhibitor PSTi8 attenuates hyperinsulinemia induced obesity and inflammation mediated insulin resistance via MAPK/NOX3-JNK pathway.Eur J Pharmacol. 2019 Dec 1;864:172723. doi: 10.1016/j.ejphar.2019.172723. Epub 2019 Oct 3.
13 Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease.Clin Pharmacol Ther. 2017 Dec;102(6):1017-1024. doi: 10.1002/cpt.733. Epub 2017 Jul 10.
14 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
15 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
16 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.