Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-ketoglutarate dehydrogenase component 4 (KGD4)
• Synonyms: Alpha-ketoglutarate dehydrogenase subunit 4
• Gene Name: KGD4
• UniProt ID: KGD4_HUMAN
• Sequence:
  MMGSKMASASRVVQVVKPHTPLIRFPDRRDNPKPNVSEALRSAGLPSHSSVISQHSKGSK
  SPDLLMYQGPPDTAEIIKTLPQKYRRKLVSQEEMEFIQRGGPE
• Function: Molecular adapter that is necessary to form a stable 2-oxoglutarate dehydrogenase enzyme complex (OGDHC). Enables the specific recruitment of E3 subunit to E2 subunit in the 2-oxoglutarate dehydrogenase complex (OGDHC).
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[8]

2 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 increases the methylation of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Alpha-ketoglutarate dehydrogenase component 4 (KGD4).	[7]

References

• [1] 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.
• [2] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] 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.
• [5] 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.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.