Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4717TF)

• DOT Name: NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2)
• Synonyms: Complex I-AGGG; CI-AGGG; NADH-ubiquinone oxidoreductase AGGG subunit
• Gene Name: NDUFB2
• Related Disease:
  Behcet disease
  Carpal tunnel syndrome
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Ischemia
  Graves disease
  Hashimoto thyroiditis
  Schistosomiasis
• UniProt ID: NDUB2_HUMAN
• PDB ID: 5XTC; 5XTD; 5XTH; 5XTI
• Pfam ID: PF14813
• Sequence:
  MSALTRLASFARVGGRLFRSGCARTAGDGGVRHAGGGVHIEPRYRQFPQLTRSQVFQSEF
  FSGLMWFWILWRFWHDSEEVLGHFPYPDPSQWTDEELGIPPDDED
• Function: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Complex I biogenesis (R-HSA-6799198)
  Respiratory electron transport (R-HSA-611105)
• BioCyc Pathway: MetaCyc:HS01679-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Strong	Genetic Variation	[1]
Carpal tunnel syndrome	DISHQ3BE	Strong	Genetic Variation	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Ischemia	DIS5XOOY	Strong	Biomarker	[4]
Graves disease	DISU4KOQ	moderate	Biomarker	[5]
Hashimoto thyroiditis	DIS77CDF	moderate	Biomarker	[5]
Schistosomiasis	DIS6PD44	Limited	Genetic Variation	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2) affects the response to substance of Paclitaxel.	[24]
Vinblastine	DM5TVS3	Approved	NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2) affects the response to substance of Vinblastine.	[24]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[18]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[13]
Marinol	DM70IK5	Approved	Marinol increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[14]
Selenium	DM25CGV	Approved	Selenium decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[17]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 2, mitochondrial (NDUFB2).	[23]

References

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• [2] The COL5A1 gene is associated with increased risk of carpal tunnel syndrome.Clin Rheumatol. 2015 Apr;34(4):767-74. doi: 10.1007/s10067-014-2727-7. Epub 2014 Jun 26.
• [3] Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients.PLoS One. 2011;6(11):e28113. doi: 10.1371/journal.pone.0028113. Epub 2011 Nov 22.
• [4] Differential-display polymerase chain reaction identifies nicotinamide adenine dinucleotide-ubiquinone oxidoreductase as an ischemia/reperfusion-regulated gene in cardiomyocytes.Chest. 2004 Jan;125(1):228-35. doi: 10.1378/chest.125.1.228.
• [5] Association of interleukin-17A and -17F gene single-nucleotide polymorphisms with autoimmune thyroid diseases.Autoimmunity. 2012 Nov;45(7):533-9. doi: 10.3109/08916934.2012.702814. Epub 2012 Aug 17.
• [6] Ficolin-2 levels and FCN2 genetic polymorphisms as a susceptibility factor in schistosomiasis.J Infect Dis. 2012 Aug 15;206(4):562-70. doi: 10.1093/infdis/jis396. Epub 2012 Jun 12.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [17] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):216-24.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.