Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7QSEWT)

• DOT Name: Vitamin K epoxide reductase complex subunit 1-like protein 1
• Synonyms: VKORC1-like protein 1; EC 1.17.4.4
• Gene Name: VKORC1L1
• UniProt ID: VKORL_HUMAN
• EC Number: 1.17.4.4
• Pfam ID: PF07884
• Sequence:
  MAAPVLLRVSVPRWERVARYAVCAAGILLSIYAYHVEREKERDPEHRALCDLGPWVKCSA
  ALASRWGRGFGLLGSIFGKDGVLNQPNSVFGLIFYILQLLLGMTASAVAALILMTSSIMS
  VVGSLYLAYILYFVLKEFCIICIVTYVLNFLLLIINYKRLVYLNEAWKRQLQPKQD
• Function: Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K, and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.
• KEGG Pathway:
  Ubiquinone and other terpenoid-quinone biosynthesis (hsa00130)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Metabolism of vitamin K (R-HSA-6806664)
• BioCyc Pathway: MetaCyc:G66-30969-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Phytonadione	DM8HDOL	Approved	Vitamin K epoxide reductase complex subunit 1-like protein 1 increases the reduction of Phytonadione.	[5]

11 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 Vitamin K epoxide reductase complex subunit 1-like protein 1.	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[3]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[4]
Dicumarol	DMFQCB1	Approved	Dicumarol decreases the activity of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[5]
Acenocoumarol	DMH75KV	Approved	Acenocoumarol decreases the activity of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[5]
Phenindione	DM2PYNR	Approved	Phenindione decreases the activity of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[5]
Phenprocoumon	DMDO279	Approved	Phenprocoumon decreases the activity of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[7]
Benzotetronic acid	DM4OKXI	Investigative	Benzotetronic acid decreases the activity of Vitamin K epoxide reductase complex subunit 1-like protein 1.	[5]

References

• [1] 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.
• [2] 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.
• [3] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites. Blood Adv. 2018 Mar 27;2(6):691-702.
• [6] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.