Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRX2NTA)

• DOT Name: Echinoderm microtubule-associated protein-like 2 (EML2)
• Synonyms: EMAP-2; HuEMAP-2
• Gene Name: EML2
• Related Disease:
  Bronchopulmonary dysplasia
  Carcinoma
  Pancreatic cancer
  Neoplasm
• UniProt ID: EMAL2_HUMAN
• PDB ID: 4CGB
• Pfam ID: PF03451 ; PF00400
• Sequence:
  MSSFGAGKTKEVIFSVEDGSVKMFLRGRPVPMMIPDELAPTYSLDTRSELPSCRLKLEWV
  YGYRGRDCRANLYLLPTGEIVYFVASVAVLYSVEEQRQRHYLGHNDDIKCLAIHPDMVTI
  ATGQVAGTTKEGKPLPPHVRIWDSVSLSTLHVLGLGVFDRAVCCVGFSKSNGGNLLCAVD
  ESNDHMLSVWDWAKETKVVDVKCSNEAVLVATFHPTDPTVLITCGKSHIYFWTLEGGSLS
  KRQGLFEKHEKPKYVLCVTFLEGGDVVTGDSGGNLYVWGKGGNRITQAVLGAHDGGVFGL
  CALRDGTLVSGGGRDRRVVLWGSDYSKLQEVEVPEDFGPVRTVAEGHGDTLYVGTTRNSI
  LQGSVHTGFSLLVQGHVEELWGLATHPSRAQFVTCGQDKLVHLWSSDSHQPLWSRIIEDP
  ARSAGFHPSGSVLAVGTVTGRWLLLDTETHDLVAIHTDGNEQISVVSFSPDGAYLAVGSH
  DNLVYVYTVDQGGRKVSRLGKCSGHSSFITHLDWAQDSSCFVTNSGDYEILYWDPATCKQ
  ITSADAVRNMEWATATCVLGFGVFGIWSEGADGTDINAVARSHDGKLLASADDFGKVHLF
  SYPCCQPRALSHKYGGHSSHVTNVAFLWDDSMALTTGGKDTSVLQWRVV
• Function: Tubulin binding protein that inhibits microtubule nucleation and growth, resulting in shorter microtubules.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]

15 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 Echinoderm microtubule-associated protein-like 2 (EML2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[13]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[18]
Manganese	DMKT129	Investigative	Manganese increases the expression of Echinoderm microtubule-associated protein-like 2 (EML2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Echinoderm microtubule-associated protein-like 2 (EML2).	[9]

References

• [1] Potential role for antiangiogenic proteins in the evolution of bronchopulmonary dysplasia.Antioxid Redox Signal. 2004 Feb;6(1):137-45. doi: 10.1089/152308604771978444.
• [2] Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.J Exp Med. 1999 Aug 2;190(3):341-54. doi: 10.1084/jem.190.3.341.
• [3] Enhancing cytotoxic agent activity in experimental pancreatic cancer through EMAP II combination therapy.Cancer Chemother Pharmacol. 2011 Sep;68(3):571-82. doi: 10.1007/s00280-010-1514-7. Epub 2010 Nov 26.
• [4] Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis.Microvasc Res. 2000 Jul;60(1):70-80. doi: 10.1006/mvre.2000.2249.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [10] 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.
• [11] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [12] 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.
• [13] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [14] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [15] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [19] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.