Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8RUXQ)

• DOT Name: Protein EVI2A (EVI2A)
• Synonyms: Ecotropic viral integration site 2A protein homolog; EVI-2A
• Gene Name: EVI2A
• Related Disease:
  Malignant peripheral nerve sheath tumor
  Neoplasm
  Neurofibromatosis type 1
  Endometrial carcinoma
  Multiple sclerosis
  Myeloid neoplasm
• UniProt ID: EVI2A_HUMAN
• Pfam ID: PF05399
• Sequence:
  MPTDMEHTGHYLHLAFLMTTVFSLSPGTKANYTRLWANSTSSWDSVIQNKTGRNQNENIN
  TNPITPEVDYKGNSTNMPETSHIVALTSKSEQELYIPSVVSNSPSTVQSIENTSKSHGEI
  FKKDVCAENNNNMAMLICLIIIAVLFLICTFLFLSTVVLANKVSSLRRSKQVGKRQPRSN
  GDFLASGLWPAESDTWKRTKQLTGPNLVMQSTGVLTATRERKDEEGTEKLTNKQIG
• Function: May complex with itself or/and other proteins within the membrane, to function as part of a cell-surface receptor.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Neurofibromatosis type 1	DIS53JH9	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	moderate	Genetic Variation	[3]
Multiple sclerosis	DISB2WZI	Limited	Genetic Variation	[4]
Myeloid neoplasm	DIS2YOWO	Limited	Biomarker	[2]

2 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 Protein EVI2A (EVI2A).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein EVI2A (EVI2A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein EVI2A (EVI2A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein EVI2A (EVI2A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein EVI2A (EVI2A).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein EVI2A (EVI2A).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein EVI2A (EVI2A).	[10]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Protein EVI2A (EVI2A).	[8]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Protein EVI2A (EVI2A).	[8]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Protein EVI2A (EVI2A).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein EVI2A (EVI2A).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein EVI2A (EVI2A).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein EVI2A (EVI2A).	[8]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Protein EVI2A (EVI2A).	[8]

References

• [1] Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
• [2] Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels.J Virol. 1995 Aug;69(8):5095-102. doi: 10.1128/JVI.69.8.5095-5102.1995.
• [3] Identification of nine new susceptibility loci for endometrial cancer.Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7.
• [4] Single strand conformation analysis of two genes contained within the first intron of the neurofibromatosis type I gene in patients with multiple sclerosis.Neuropathol Appl Neurobiol. 1995 Jun;21(3):201-7. doi: 10.1111/j.1365-2990.1995.tb01051.x.
• [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] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [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] DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer thapsigargin based on comparative gene expression profiling in Jurkat T cells. Toxicol Lett. 2014 Jan 30;224(3):395-406. doi: 10.1016/j.toxlet.2013.11.005. Epub 2013 Nov 15.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.