Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT98X1OE)

• DOT Name: Protein EVI2B (EVI2B)
• Synonyms: Ecotropic viral integration site 2B protein homolog; EVI-2B; CD antigen CD361
• Gene Name: EVI2B
• Related Disease:
  Neurofibroma
  Neurofibromatosis
  Neoplasm
• UniProt ID: EVI2B_HUMAN
• Sequence:
  MDPKYFILILFCGHLNNTFFSKTETITTEKQSQPTLFTSSMSQVLANSQNTTGNPLGQPT
  QFSDTFSGQSISPAKVTAGQPTPAVYTSSEKPEAHTSAGQPLAYNTKQPTPIANTSSQQA
  VFTSARQLPSARTSTTQPPKSFVYTFTQQSSSVQIPSRKQITVHNPSTQPTSTVKNSPRS
  TPGFILDTTSNKQTPQKNNYNSIAAILIGVLLTSMLVAIIIIVLWKCLRKPVLNDQNWAG
  RSPFADGETPDICMDNIRENEISTKRTSIISLTPWKPSKSTLLADDLEIKLFESSENIED
  SNNPKTEKIKDQVNGTSEDSADGSTVGTAVSSSDDADLPPPPPLLDLEGQESNQSDKPTM
  TIVSPLPNDSTSLPPSLDCLNQDCGDHKSEIIQSFPPLDSLNLPLPPVDFMKNQEDSNLE
  IQCQEFSIPPNSDQDLNESLPPPPAELL
• Function: Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells.
• Tissue Specificity: Bone marrow, peripheral blood mononuclear cells, fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cell lines. Strongly expressed in granulocytic cells, and weakly on lymphocytes cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurofibroma	DISIJJMH	moderate	Altered Expression	[1]
Neurofibromatosis	DIS5N2R6	moderate	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

10 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 Protein EVI2B (EVI2B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein EVI2B (EVI2B).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein EVI2B (EVI2B).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein EVI2B (EVI2B).	[3]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Protein EVI2B (EVI2B).	[6]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Protein EVI2B (EVI2B).	[7]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Protein EVI2B (EVI2B).	[8]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Protein EVI2B (EVI2B).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein EVI2B (EVI2B).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein EVI2B (EVI2B).	[11]

References

• [1] EVI2B, a gene lying in an intron of the neurofibromatosis type 1 (NF1) gene, is as the NF1 gene involved in differentiation of melanocytes and keratinocytes and is overexpressed in cells derived from NF1 neurofibromas.DNA Cell Biol. 1999 May;18(5):345-56. doi: 10.1089/104454999315240.
• [2] cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene.Genomics. 1991 Mar;9(3):446-60. doi: 10.1016/0888-7543(91)90410-g.
• [3] Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [6] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [7] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [8] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [9] Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
• [10] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.