Details of Drug Off-Target (DOT)

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

• DOT Name: NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4)
• Synonyms: Complex I-B15; CI-B15; NADH-ubiquinone oxidoreductase B15 subunit
• Gene Name: NDUFB4
• UniProt ID: NDUB4_HUMAN
• PDB ID: 5XTC; 5XTD; 5XTH; 5XTI
• Pfam ID: PF07225
• Sequence:
  MSFPKYKPSSLRTLPETLDPAEYNISPETRRAQAERLAIRAQLKREYLLQYNDPNRRGLI
  ENPALLRWAYARTINVYPNFRPTPKNSLMGALCGFGPLIFIYYIIKTERDRKEKLIQEGK
  LDRTFHLSY
• 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:HS00843-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of NADH dehydrogenase 1 beta subcomplex subunit 4 (NDUFB4).	[2]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.