Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ7PORS)

• DOT Name: Selenoprotein M (SELENOM)
• Synonyms: SelM
• Gene Name: SELENOM
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Clear cell renal carcinoma
  Hepatocellular carcinoma
  Renal cell carcinoma
• UniProt ID: SELM_HUMAN
• Pfam ID: PF08806
• Sequence:
  MSLLLPPLALLLLLAALVAPATAATAYRPDWNRLSGLTRARVETCGGUQLNRLKEVKAFV
  TQDIPFYHNLVMKHLPGADPELVLLGRRYEELERIPLSEMTREEINALVQELGFYRKAAP
  DAQVPPEYVWAPAKPPEETSDHADL
• Function: May function as a thiol-disulfide oxidoreductase that participates in disulfide bond formation.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Selenoprotein M (SELENOM) affects the response to substance of Acetaminophen.	[17]

12 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 Selenoprotein M (SELENOM).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Selenoprotein M (SELENOM).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Selenoprotein M (SELENOM).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Selenoprotein M (SELENOM).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Selenoprotein M (SELENOM).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Selenoprotein M (SELENOM).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Selenoprotein M (SELENOM).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Selenoprotein M (SELENOM).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Selenoprotein M (SELENOM).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Selenoprotein M (SELENOM).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Selenoprotein M (SELENOM).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Selenoprotein M (SELENOM).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Selenoprotein M (SELENOM).	[9]

References

• [1] Selenoprotein M stimulates the proliferative and metastatic capacities of renal cell carcinoma through activating the PI3K/AKT/mTOR pathway.Cancer Med. 2019 Aug;8(10):4836-4844. doi: 10.1002/cam4.2403. Epub 2019 Jul 5.
• [2] Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer's disease.Neurochem Res. 2005 Aug;30(8):1009-19. doi: 10.1007/s11064-005-6787-6.
• [3] Structure-function relationship and evolutionary history of the human selenoprotein M (SelM) found over-expressed in hepatocellular carcinoma.Biochim Biophys Acta. 2014 Feb;1844(2):447-56. doi: 10.1016/j.bbapap.2013.12.001. Epub 2013 Dec 9.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [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] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [13] 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.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] 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.
• [16] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [17] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.