Details of Drug Off-Target (DOT)

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

• DOT Name: Thioredoxin reductase-like selenoprotein T (SELENOT)
• Synonyms: SelT; EC 1.8.1.9
• Gene Name: SELENOT
• Related Disease:
  Parkinson disease
  Schistosomiasis
• UniProt ID: SELT_HUMAN
• EC Number: 1.8.1.9
• Pfam ID: PF10262
• Sequence:
  MRLLLLLLVAASAMVRSEASANLGGVPSKRLKMQYATGPLLKFQICVSUGYRRVFEEYMR
  VISQRYPDIRIEGENYLPQPIYRHIASFLSVFKLVLIGLIIVGKDPFAFFGMQAPSIWQW
  GQENKVYACMMVFFLSNMIENQCMSTGAFEITLNDVPVWSKLESGHLPSMQQLVQILDNE
  MKLNVHMDSIPHHRS
• Function: Selenoprotein with thioredoxin reductase-like oxidoreductase activity. Protects dopaminergic neurons against oxidative stress and cell death. Involved in ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion. Plays a role in fibroblast anchorage and redox regulation. In gastric smooth muscle, modulates the contraction processes through the regulation of calcium release and MYLK activation. In pancreatic islets, involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP-induced insulin secretion.
• Tissue Specificity: Ubiquitous. Highly expressed in the endocrine pancreas.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Biomarker	[1]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Thioredoxin reductase-like selenoprotein T (SELENOT).	[9]

References

• [1] The Thioredoxin-Like Family of Selenoproteins: Implications in Aging and Age-Related Degeneration.Biol Trace Elem Res. 2019 Mar;188(1):189-195. doi: 10.1007/s12011-018-1521-9. Epub 2018 Sep 18.
• [2] Fragment-Based Discovery of a Regulatory Site in Thioredoxin Glutathione Reductase Acting as "Doorstop" for NADPH Entry.ACS Chem Biol. 2018 Aug 17;13(8):2190-2202. doi: 10.1021/acschembio.8b00349. Epub 2018 Jun 11.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] 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.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.