Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBQ3KQE)

• DOT Name: BRCA2-interacting transcriptional repressor EMSY (EMSY)
• Gene Name: EMSY
• Related Disease:
  Breast neoplasm
  Male breast carcinoma
  Allergic rhinitis
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Crohn disease
  Familial prostate carcinoma
  Polycystic ovarian syndrome
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Undifferentiated carcinoma
  Advanced cancer
  Food allergy
  Hereditary breast carcinoma
  Hereditary breast ovarian cancer syndrome
  Neoplasm
  Asthma
  Eosinophilic esophagitis
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: EMSY_HUMAN
• PDB ID: 1UTU; 1UZ3; 2FMM
• Pfam ID: PF03735
• Sequence:
  MPVVWPTLLDLSRDECKRILRKLELEAYAGVISALRAQGDLTKEKKDLLGELSKVLSIST
  ERHRAEVRRAVNDERLTTIAHNMSGPNSSSEWSIEGRRLVPLMPRLVPQTAFTVTANAVA
  NAAIQHNASLPVPAETGSKEVVCYSYTSTTSTPTSTPVPSGSIATVKSPRPASPASNVVV
  LPSGSTVYVKSVSCSDEDEKPRKRRRTNSSSSSPVVLKEVPKAVVPVSKTITVPVSGSPK
  MSNIMQSIANSLPPHMSPVKITFTKPSTQTTNTTTQKVIIVTTSPSSTFVPNILSKSHNY
  AAVTKLVPTSVIASTTQKPPVVITASQSSLVSNSSSGSSSSTPSPIPNTVAVTAVVSSTP
  SVVMSTVAQGVSTSAIKMASTRLPSPKSLVSAPTQILAQFPKQHQQSPKQQLYQVQQQTQ
  QQVAQPSPVSHQQQPQQSPLPPGIKPTIQIKQESGVKIITQQVQPSKILPKPVTATLPTS
  SNSPIMVVSSNGAIMTTKLVTTPTGTQATYTRPTVSPSIGRMAATPGAATYVKTTSGSII
  TVVPKSLATLGGKIISSNIVSGTTTKITTIPMTSKPNVIVVQKTTGKGTTIQGLPGKNVV
  TTLLNAGGEKTIQTVPTGAKPAILTATRPITKMIVTQPKGIGSTVQPAAKIIPTKIVYGQ
  QGKTQVLIKPKPVTFQATVVSEQTRQLVTETLQQASRVAEAGNSSIQEGKEEPQNYTDSS
  SSSTESSQSSQDSQPVVHVIASRRQDWSEHEIAMETSPTIIYQDVSSESQSATSTIKALL
  ELQQTTVKEKLESKPRQPTIDLSQMAVPIQMTQEKRHSPESPSIAVVESELVAEYITTER
  TDEGTEVAFPLLVSHRSQPQQPSQPQRTLLQHVAQSQTATQTSVVVKSIPASSPGAITHI
  MQQALSSHTAFTKHSEELGTEEGEVEEMDTLDPQTGLFYRSALTQSQSAKQQKLSQPPLE
  QTQLQVKTLQCFQTKQKQTIHLQADQLQHKLPQMPQLSIRHQKLTPLQQEQAQPKPDVQH
  TQHPMVAKDRQLPTLMAQPPQTVVQVLAVKTTQQLPKLQQAPNQPKIYVQPQTPQSQMSL
  PASSEKQTASQVEQPIITQGSSVTKITFEGRQPPTVTKITGGSSVPKLTSPVTSISPIQA
  SEKTAVSDILKMSLMEAQIDTNVEHMIVDPPKKALATSMLTGEAGSLPSTHMVVAGMANS
  TPQQQKCRESCSSPSTVGSSLTTRKIDPPAVPATGQFMRIQNVGQKKAEESPAEIIIQAI
  PQYAIPCHSSSNVVVEPSGLLELNNFTSQQLDDEETAMEQDIDSSTEDGTEPSPSQSSAE
  RS
• Function: Regulator which is able to repress transcription, possibly via its interaction with a multiprotein chromatin remodeling complex that modifies the chromatin. Its interaction with BRCA2 suggests that it may play a central role in the DNA repair function of BRCA2. Mediates ligand-dependent transcriptional activation by nuclear hormone receptors.

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Genetic Variation	[1]
Male breast carcinoma	DISUNQ2Q	Definitive	Biomarker	[2]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[3]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[8]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[10]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[9]
Undifferentiated carcinoma	DISIAZST	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[11]
Food allergy	DISMQ1BP	moderate	Genetic Variation	[12]
Hereditary breast carcinoma	DISAEZT5	moderate	Genetic Variation	[5]
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Altered Expression	[13]
Neoplasm	DISZKGEW	moderate	Biomarker	[11]
Asthma	DISW9QNS	Limited	Biomarker	[14]
Eosinophilic esophagitis	DISR8WSB	Limited	Biomarker	[15]
Lung cancer	DISCM4YA	Limited	Biomarker	[16]
Lung carcinoma	DISTR26C	Limited	Biomarker	[16]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[17]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[18]
Thyroid tumor	DISLVKMD	Limited	Genetic Variation	[18]

4 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 BRCA2-interacting transcriptional repressor EMSY (EMSY).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[21]
Selenium	DM25CGV	Approved	Selenium decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[28]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of BRCA2-interacting transcriptional repressor EMSY (EMSY).	[29]

References

• [1] EMSY and CCND1 amplification in familial breast cancer: from the Ontario site of the Breast Cancer Family Registry.Breast Cancer Res Treat. 2011 Jun;127(3):831-9. doi: 10.1007/s10549-011-1380-y. Epub 2011 Feb 15.
• [2] EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations.Breast Cancer Res Treat. 2016 Nov;160(1):181-186. doi: 10.1007/s10549-016-3976-8. Epub 2016 Sep 15.
• [3] The association between sixteen genome-wide association studies-related allergic diseases loci and childhood allergic rhinitis in a Chinese Han population.Cytokine. 2018 Nov;111:162-170. doi: 10.1016/j.cyto.2018.08.022. Epub 2018 Aug 28.
• [4] EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis.J Allergy Clin Immunol. 2019 Aug;144(2):470-481. doi: 10.1016/j.jaci.2019.05.024. Epub 2019 May 31.
• [5] Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families.BMC Cancer. 2017 Jul 24;17(1):496. doi: 10.1186/s12885-017-3488-x.
• [6] Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas.Gynecol Oncol. 2006 Feb;100(2):264-70. doi: 10.1016/j.ygyno.2005.08.026. Epub 2005 Oct 19.
• [7] microRNA-451a regulates colorectal cancer proliferation in response to radiation.BMC Cancer. 2018 May 3;18(1):517. doi: 10.1186/s12885-018-4370-1.
• [8] Multidimensional prognostic risk assessment identifies association between IL12B variation and surgery in Crohn's disease.Inflamm Bowel Dis. 2013 Jul;19(8):1662-70. doi: 10.1097/MIB.0b013e318281f275.
• [9] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [10] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [11] The function of EMSY in cancer development.Tumour Biol. 2014 Jun;35(6):5061-6. doi: 10.1007/s13277-013-1584-3. Epub 2014 Mar 9.
• [12] Genetic determinants of paediatric food allergy: A systematic review.Allergy. 2019 Sep;74(9):1631-1648. doi: 10.1111/all.13767. Epub 2019 Apr 2.
• [13] EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases.Mol Genet Genomics. 2011 Apr;285(4):325-40. doi: 10.1007/s00438-011-0612-5. Epub 2011 Mar 16.
• [14] Genetic variants of the C11orf30-LRRC32 region are associated with childhood asthma in the Chinese population.Allergol Immunopathol (Madr). 2020 Jul-Aug;48(4):390-394. doi: 10.1016/j.aller.2019.09.002. Epub 2019 Dec 5.
• [15] From genetics to treatment of eosinophilic esophagitis.Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):417-25. doi: 10.1097/ACI.0000000000000200.
• [16] The EMSY Gene Collaborates with CCND1 in Non-Small Cell Lung Carcinogenesis.Int J Med Sci. 2017 Jun 23;14(7):675-679. doi: 10.7150/ijms.19355. eCollection 2017.
• [17] Expressional profiling of prostate cancer risk SNPs at 11q13.5 identifies DGAT2 as a new target gene.Genes Chromosomes Cancer. 2016 Aug;55(8):661-73. doi: 10.1002/gcc.22368. Epub 2016 May 24.
• [18] Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma.J Endocrinol Invest. 2008 Jul;31(7):618-23. doi: 10.1007/BF03345613.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [23] 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.
• [24] BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
• [25] 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.
• [26] 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.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [29] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.