Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3J7CJB)

• DOT Name: Genetic suppressor element 1 (GSE1)
• Gene Name: GSE1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Alopecia
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: GSE1_HUMAN
• Pfam ID: PF12540
• Sequence:
  MKGMSHEPKSPSLGMLSTATRTTATVNPLTPSPLNGALVPSGSPATSSALSAQAAPSSSF
  AAALRKLAKQAEEPRGSSLSSESSPVSSPATNHSSPASTPKRVPMGPIIVPPGGHSVPST
  PPVVTIAPTKTVNGVWRSESRQDAGSRSSSGGRERLIVEPPLPQEKAGGPAIPSHLLSTP
  YPFGLSPSSVVQDSRFPPLNLQRPVHHVVPPSTVTEDYLRSFRPYHTTDDLRMSSLPPLG
  LDPATAAAYYHPSYLAPHPFPHPAFRMDDSYCLSALRSPFYPIPTPGSLPPLHPSAMHLH
  LSGVRYPPELSHSSLAALHSERMSGLSAERLQMDEELRREREREREREREREADREREKE
  REREREKEREQEKEREREKERERELERQREQRAREKELLAAKALEPSFLPVAELHGLRGH
  ATEERGKPSEQLTPTRAEKLKDAGLQAPKPVQHPLHPVPTPHHTVPSLISNHGIFSLPSS
  SAATALLIQRTNEEEKWLARQRRLRQEKEDRQSQVSEFRQQVLEQHLDMGRPPVPAEAEH
  RPESTTRPGPNRHEPGGRDPPQHFGGPPPLISPKPQLHAAPTALWNPVSLMDNTLETRRA
  ESHSLHSHPAAFEPSRQAAVPLVKVERVFCPEKAEEGPRKREPAPLDKYQPPPPPPREGG
  SLEHQPFLPGPGPFLAELEKSTQTILGQQRASLPQAATFGELSGPLKPGSPYRPPVPRAP
  DPAYIYDEFLQQRRRLVSKLDLEERRRREAQEKGYYYDLDDSYDESDEEEVRAHLRCVAE
  QPPLKLDTSSEKLEFLQLFGLTTQQQKEELVAQKRRKRRRMLRERSPSPPTIQSKRQTPS
  PRLALSTRYSPDEMNNSPNFEEKKKFLTIFNLTHISAEKRKDKERLVEMLRAMKQKALSA
  AVADSLTNSPRDSPAVSLSEPATQQASLDVEKPVGVAASLSDIPKAAEPGKLEQVRPQEL
  SRVQELAPASGEKARLSEAPGGKKSLSMLHYIRGAAPKDIPVPLSHSTNGKSKPWEPFVA
  EEFAHQFHESVLQSTQKALQKHKGSVAVLSAEQNHKVDTSVHYNIPELQSSSRAPPPQHN
  GQQEPPTARKGPPTQELDRDSEEEEEEDDEDGEDEEEVPKRKWQGIEAVFEAYQEHIEEQ
  NLERQVLQTQCRRLEARHYSLSLTAEQLSHSVAELRSQKQKMVSERERLQAELDHLRKCL
  ALPAMHWPRGYLKGYPR

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Alopecia	DIS37HU4	Limited	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Genetic suppressor element 1 (GSE1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Genetic suppressor element 1 (GSE1).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Genetic suppressor element 1 (GSE1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Genetic suppressor element 1 (GSE1).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Genetic suppressor element 1 (GSE1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Genetic suppressor element 1 (GSE1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Genetic suppressor element 1 (GSE1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Genetic suppressor element 1 (GSE1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Genetic suppressor element 1 (GSE1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Genetic suppressor element 1 (GSE1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Genetic suppressor element 1 (GSE1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Genetic suppressor element 1 (GSE1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Genetic suppressor element 1 (GSE1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Genetic suppressor element 1 (GSE1).	[15]
Rigosertib	DMOSTXF	Phase 3	Rigosertib affects the expression of Genetic suppressor element 1 (GSE1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Genetic suppressor element 1 (GSE1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Genetic suppressor element 1 (GSE1).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Genetic suppressor element 1 (GSE1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Genetic suppressor element 1 (GSE1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Genetic suppressor element 1 (GSE1).	[23]

References

• [1] GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion.Biochem Biophys Res Commun. 2016 Feb 26;471(1):123-8. doi: 10.1016/j.bbrc.2016.01.168. Epub 2016 Jan 30.
• [2] Identification of candidate genes carrying polymorphisms associated with the risk of colorectal cancer by analyzing the colorectal mutome and microRNAome.Cancer. 2012 Oct 1;118(19):4670-80. doi: 10.1002/cncr.27435. Epub 2012 Jan 26.
• [3] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [4] GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis.J Biol Chem. 2018 Mar 16;293(11):3949-3964. doi: 10.1074/jbc.RA117.001103. Epub 2018 Jan 24.
• [5] 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.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] 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.
• [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] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [17] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [18] 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.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] 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.
• [22] 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.
• [23] 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.