Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEWIU9)

DOT Name	Selenoprotein S (SELENOS)
Synonyms	SelS; VCP-interacting membrane protein
Gene Name	SELENOS
Related Disease	Cerebrovascular disease ( ) Metabolic disorder ( ) Advanced cancer ( ) Alpha-1 antitrypsin deficiency ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Colitis ( ) Colorectal carcinoma ( ) Gastric cancer ( ) Hashimoto thyroiditis ( ) Hepatocellular carcinoma ( ) Insulinoma ( ) Non-insulin dependent diabetes ( ) Non-small-cell lung cancer ( ) Obesity ( ) Prostate cancer ( ) Prostate neoplasm ( ) Stomach cancer ( ) Type-1/2 diabetes ( ) Ulcerative colitis ( ) Breast cancer ( ) Breast carcinoma ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Asthma ( ) Atopic dermatitis ( ) Cardiovascular disease ( ) Neuroblastoma ( ) Rheumatoid arthritis ( ) Type-1 diabetes ( )
UniProt ID	SELS_HUMAN
PDB ID	2Q2F; 5KIU; 5KIY; 6DO4
Pfam ID	PF06936
Sequence	MERQEESLSARPALETEGLRFLHTTVGSLLATYGWYIVFSCILLYVVFQKLSARLRALRQ RQLDRAAAAVEPDVVVKRQEALAAARLKMQEELNAQVEKHKEKLKQLEEEKRRQKIEMWD SMQEGKSYKGNAKKPQEEDSPGPSTSSVLKRKSDRKPLRGGGYNPLSGEGGGACSWRPGR RGPSSGGUG
Function	Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Probably acts by serving as a linker between DERL1, which mediates the retrotranslocation of misfolded proteins into the cytosol, and the ATPase complex VCP, which mediates the translocation and ubiquitination.
KEGG Pathway	Protein processing in endoplasmic reticulum (hsa04141 )
Reactome Pathway	E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cerebrovascular disease	DISAB237	Definitive	Genetic Variation	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alpha-1 antitrypsin deficiency	DISQKEHW	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[8]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[9]
Hashimoto thyroiditis	DIS77CDF	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Insulinoma	DISIU1JS	Strong	Biomarker	[12]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[16]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[17]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[18]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[18]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[19]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[19]
Asthma	DISW9QNS	Limited	Genetic Variation	[20]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[20]
Cardiovascular disease	DIS2IQDX	Limited	Genetic Variation	[21]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[23]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[24]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Selenoprotein S (SELENOS).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Selenoprotein S (SELENOS).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Selenoprotein S (SELENOS).	[37]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Selenoprotein S (SELENOS).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Selenoprotein S (SELENOS).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Selenoprotein S (SELENOS).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Selenoprotein S (SELENOS).	[29]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Selenoprotein S (SELENOS).	[30]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Selenoprotein S (SELENOS).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Selenoprotein S (SELENOS).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Selenoprotein S (SELENOS).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Selenoprotein S (SELENOS).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Selenoprotein S (SELENOS).	[36]
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⏷ Show the Full List of 10 Drug(s)

References

1	No association of the -105 promoter polymorphism of the selenoprotein S encoding gene SEPS1 with cerebrovascular disease.Eur J Neurol. 2007 Oct;14(10):1173-5. doi: 10.1111/j.1468-1331.2007.01898.x.
2	Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors.Metabolism. 2011 Jan;60(1):114-20. doi: 10.1016/j.metabol.2010.05.011.
3	Single nucleotide polymorphism in the SEPS1 gene may contribute to the risk of various human diseases: a meta-analysis.Ann Hum Biol. 2016 Sep;43(5):469-79. doi: 10.3109/03014460.2015.1070903. Epub 2015 Sep 18.
4	Is there a therapeutic role for selenium in alpha-1 antitrypsin deficiency?.Nutrients. 2013 Mar 11;5(3):758-70. doi: 10.3390/nu5030758.
5	Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology.J Alzheimers Dis. 2017;55(2):749-762. doi: 10.3233/JAD-151208.
6	Selenium in the prevention of atherosclerosis and its underlying mechanisms.Metallomics. 2017 Jan 25;9(1):21-37. doi: 10.1039/c6mt00195e.
7	The role of the selenoprotein S (SELS) gene -105G>A promoter polymorphism in inflammatory bowel disease and regulation of SELS gene expression in intestinal inflammation.Tissue Antigens. 2007 Sep;70(3):238-46. doi: 10.1111/j.1399-0039.2007.00888.x.
8	The influence of selenium and selenoprotein gene variants on colorectal cancer risk.Mutagenesis. 2012 Mar;27(2):177-86. doi: 10.1093/mutage/ger058.
9	Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population.BMC Gastroenterol. 2009 Jan 13;9:2. doi: 10.1186/1471-230X-9-2.
10	Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis.Thyroid. 2017 May;27(5):597-610. doi: 10.1089/thy.2016.0635. Epub 2017 Apr 6.
11	Secretion of the glucose-regulated selenoprotein SEPS1 from hepatoma cells.Biochem Biophys Res Commun. 2007 May 11;356(3):636-41. doi: 10.1016/j.bbrc.2007.03.018. Epub 2007 Mar 12.
12	Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells.Cell Physiol Biochem. 2018;51(5):2185-2197. doi: 10.1159/000495865. Epub 2018 Dec 7.
13	Correlation between SEPS1 gene polymorphism and type 2 diabetes mellitus: A preliminary study.J Clin Lab Anal. 2019 Oct;33(8):e22967. doi: 10.1002/jcla.22967. Epub 2019 Jul 2.
14	A combination of functional polymorphisms in the CASP8, MMP1, IL10 and SEPS1 genes affects risk of non-small cell lung cancer.Lung Cancer. 2011 Feb;71(2):123-9. doi: 10.1016/j.lungcan.2010.04.016. Epub 2010 May 14.
15	Selenate Prevents Adipogenesis through Induction of Selenoprotein S and Attenuation of Endoplasmic Reticulum Stress.Molecules. 2018 Nov 5;23(11):2882. doi: 10.3390/molecules23112882.
16	Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
17	Association of genetic polymorphisms of SelS with Type 2 diabetes in a Chinese population.Biosci Rep. 2018 Nov 28;38(6):BSR20181696. doi: 10.1042/BSR20181696. Print 2018 Dec 21.
18	SEPP1 influences breast cancer risk among women with greater native american ancestry: the breast cancer health disparities study.PLoS One. 2013 Nov 20;8(11):e80554. doi: 10.1371/journal.pone.0080554. eCollection 2013.
19	Variation in the selenoprotein S gene locus is associated with coronary heart disease and ischemic stroke in two independent Finnish cohorts.Hum Genet. 2007 Nov;122(3-4):355-65. doi: 10.1007/s00439-007-0402-7. Epub 2007 Jul 20.
20	Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes.Diabetes Metab Res Rev. 2011 Nov;27(8):838-43. doi: 10.1002/dmrr.1259.
21	Effect of single nucleotide polymorphisms in SEPS1 and SEPP1 on expression in the protein level in metabolic syndrome in subjects with cardiovascular disease.Mol Biol Rep. 2019 Dec;46(6):5685-5693. doi: 10.1007/s11033-019-05000-5. Epub 2019 Sep 21.
22	Selenoprotein S is required for clearance of C99 through endoplasmic reticulum-associated degradation.Biochem Biophys Res Commun. 2017 Apr 29;486(2):444-450. doi: 10.1016/j.bbrc.2017.03.060. Epub 2017 Mar 16.
23	Evidence of epistasis between interleukin 1 and selenoprotein-S with susceptibility to rheumatoid arthritis.Ann Rheum Dis. 2009 Sep;68(9):1494-7. doi: 10.1136/ard.2008.090001. Epub 2008 Aug 26.
24	Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases.BMC Genomics. 2008 Jul 14;9:329. doi: 10.1186/1471-2164-9-329.
25	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
26	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.
27	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
28	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29	The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
30	Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013 Dec;33(12):1460-7. doi: 10.1002/jat.2812. Epub 2012 Sep 20.
31	THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
32	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.
33	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.
34	Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
35	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
36	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
37	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.