Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT0UJAS)

• DOT Name: Mesoderm induction early response protein 1 (MIER1)
• Synonyms: Early response 1; Er1; Mi-er1; hMi-er1
• Gene Name: MIER1
• Related Disease:
  Androgen insensitivity syndrome
  Osteoporosis
  Cryptorchidism
  Non-insulin dependent diabetes
• UniProt ID: MIER1_HUMAN
• Pfam ID: PF01448 ; PF19426 ; PF00249
• Sequence:
  MAEPSVESSSPGGSATSDDHEFDPSADMLVHDFDDERTLEEEEMMEGETNFSSEIEDLAR
  EGDMPIHELLSLYGYGSTVRLPEEDEEEEEEEEEGEDDEDADNDDNSGCSGENKEENIKD
  SSGQEDETQSSNDDPSQSVASQDAQEIIRPRRCKYFDTNSEVEEESEEDEDYIPSEDWKK
  EIMVGSMFQAEIPVGICRYKENEKVYENDDQLLWDPEYLPEDKVIIFLKDASRRTGDEKG
  VEAIPEGSHIKDNEQALYELVKCNFDTEEALRRLRFNVKAAREELSVWTEEECRNFEQGL
  KAYGKDFHLIQANKVRTRSVGECVAFYYMWKKSERYDFFAQQTRFGKKKYNLHPGVTDYM
  DRLLDESESAASSRAPSPPPTASNSSNSQSEKEDGTVSTANQNGVSSNGPGEILNKEEVK
  VEGLHINGPTGGNKKPLHADMDTNGYETDNLTTDPKLAHMTARNENDFDEKSERPAKRRR
  VNSNGKESPGSSEFFQEAVSHGKFEELENTDD
• Function: Transcriptional repressor regulating the expression of a number of genes including SP1 target genes. Probably functions through recruitment of HDAC1 a histone deacetylase involved in chromatin silencing.
• Tissue Specificity: Ubiquitously expressed, but at very low levels. However, consistent level of expression are observed in heart, testis, thyroid, ovary and adrenal gland. Transcripts are up-regulated in breast carcinoma cell lines and tumor.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[1]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[2]
Cryptorchidism	DISYUD2P	Limited	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]

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 Mesoderm induction early response protein 1 (MIER1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mesoderm induction early response protein 1 (MIER1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Mesoderm induction early response protein 1 (MIER1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Mesoderm induction early response protein 1 (MIER1).	[15]

7 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 Mesoderm induction early response protein 1 (MIER1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mesoderm induction early response protein 1 (MIER1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mesoderm induction early response protein 1 (MIER1).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mesoderm induction early response protein 1 (MIER1).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Mesoderm induction early response protein 1 (MIER1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mesoderm induction early response protein 1 (MIER1).	[12]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Mesoderm induction early response protein 1 (MIER1).	[14]

References

• [1] Association between adolescent idiopathic scoliosis with double curve and polymorphisms of calmodulin1 gene/estrogen receptor- gene.Orthop Surg. 2009 Aug;1(3):222-30. doi: 10.1111/j.1757-7861.2009.00038.x.
• [2] Oestrogen receptor Rsa I gene polymorphism in osteoporosis periodontitis patients with or without dental fluorosis.Indian J Med Res. 2019 Mar;149(3):364-368. doi: 10.4103/ijmr.IJMR_1821_16.
• [3] Molecular analysis of estrogen receptor alpha gene AGATA haplotype and SNP12 in European populations: potential protective effect for cryptorchidism and lack of association with male infertility.Hum Reprod. 2007 Feb;22(2):444-9. doi: 10.1093/humrep/del391. Epub 2006 Nov 10.
• [4] Estrogen receptor alpha gene polymorphisms are associated with type 2 diabetes and fasting glucose in male subjects.Mol Cell Biochem. 2012 Jan;359(1-2):225-33. doi: 10.1007/s11010-011-1017-9. Epub 2011 Aug 12.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] 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.
• [13] 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.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] 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.