Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4CW64T)

• DOT Name: Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1)
• Synonyms: ERV-3 envelope protein; ERV3 envelope protein; ERV3-1 envelope protein; Envelope polyprotein; HERV-R envelope protein; ERV-R envelope protein; HERV-R_7q21.2 provirus ancestral Env polyprotein
• Gene Name: ERV3-1
• Related Disease:
  Choriocarcinoma
  Adenoma
  Breast cancer
  Breast carcinoma
  Endometrial carcinoma
  Epithelial ovarian cancer
  Gestational trophoblastic neoplasia
  Hydatidiform mole
  Ovarian cancer
  Ovarian neoplasm
  Pheochromocytoma
  Polyp
  Sjogren syndrome
  Systemic lupus erythematosus
  Advanced cancer
• UniProt ID: ENR1_HUMAN
• Sequence:
  MLGMNMLLITLFLLLPLSMLKGEPWEGCLHCTHTTWSGNIMTKTLLYHTYYECAGTCLGT
  CTHNQTTYSVCDPGRGQPYVCYDPKSSPGTWFEIHVGSKEGDLLNQTKVFPSGKDVVSLY
  FDVCQIVSMGSLFPVIFSSMEYYSSCHKNRYAHPACSTDSPVTTCWDCTTWSTNQQSLGP
  IMLTKIPLEPDCKTSTCNSVNLTILEPDQPIWTTGLKAPLGARVSGEEIGPGAYVYLYII
  KKTRTRSTQQFRVFESFYEHVNQKLPEPPPLASNLFAQLAENIASSLHVASCYVCGGMNM
  GDQWPWEARELMPQDNFTLTASSLEPAPSSQSIWFLKTSIIGKFCIARWGKAFTDPVGEL
  TCLGQQYYNETLGKTLWRGKSNNSESPHPSPFSRFPSLNHSWYQLEAPNTWQAPSGLYWI
  CGPQAYRQLPAKWSGACVLGTIRPSFFLMPLKQGEALGYPIYDETKRKSKRGITIGDWKD
  NEWPPERIIQYYGPATWAEDGMWGYRTPVYMLNRIIRLQAVLEIITNETAGALNLLAQQA
  TKMRNVIYQNRLALDYLLAQEEGVCGKFNLTNCCLELDDEGKVIKEITAKIQKLAHIPVQ
  TWKG
• Function: Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution. This endogenous envelope protein has lost its fusogenic properties. It can inhibit cell growth through decrease expression of cyclin B1 and increased expression of p21 in vitro; SU mediates receptor recognition; TM anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane.
• Tissue Specificity: Expressed at higher level in adrenal, sebaceous glands and placenta. Expressed at lower level in bone marrow, brain, breast, colon, heart, kidney, liver, lung, ovary, PBL, prostate, skin, spleen, testis, thymus, thyroid, trachea.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Choriocarcinoma	DISDBVNL	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Gestational trophoblastic neoplasia	DIS4EJNA	Strong	Altered Expression	[6]
Hydatidiform mole	DISKNP7O	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[2]
Polyp	DISRSLYF	Strong	Biomarker	[4]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[7]
Advanced cancer	DISAT1Z9	Disputed	Biomarker	[8]

7 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 Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1).	[13]

References

• [1] The cellular mechanism by which the human endogenous retrovirus ERV-3 env gene affects proliferation and differentiation in a human placental trophoblast model, BeWo.Placenta. 2000 Jan;21(1):73-8. doi: 10.1053/plac.1999.0443.
• [2] Tissue-specific high-level expression of human endogenous retrovirus-R in the human adrenal cortex.Pathobiology. 1998;66(5):209-15. doi: 10.1159/000028025.
• [3] Expression of human endogenous retrovirus k envelope transcripts in human breast cancer.Clin Cancer Res. 2001 Jun;7(6):1553-60.
• [4] Reactivation of codogenic endogenous retroviral (ERV) envelope genes in human endometrial carcinoma and prestages: Emergence of new molecular targets.Oncotarget. 2012 Oct;3(10):1204-19. doi: 10.18632/oncotarget.679.
• [5] Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer.Int J Cancer. 2007 Jan 1;120(1):81-90. doi: 10.1002/ijc.22256.
• [6] Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.Placenta. 2016 Mar;39:116-24. doi: 10.1016/j.placenta.2016.01.011. Epub 2016 Jan 14.
• [7] The expression of human endogenous retrovirus-3 in fetal cardiac tissue and antibodies in congenital heart block.Clin Exp Immunol. 1996 Jun;104(3):388-93.
• [8] Endogenous Retrovirus 3 - History, Physiology, and Pathology.Front Microbiol. 2018 Jan 15;8:2691. doi: 10.3389/fmicb.2017.02691. eCollection 2017.
• [9] 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.
• [10] Effects of Bisphenol A on endogenous retroviral envelopes expression and trophoblast fusion in BeWo cells. Reprod Toxicol. 2019 Oct;89:35-44. doi: 10.1016/j.reprotox.2019.07.001. Epub 2019 Jul 3.
• [11] Expression and Regulation of the Endogenous Retrovirus 3 in Hodgkin's Lymphoma Cells. Front Oncol. 2013 Jul 10;3:179. doi: 10.3389/fonc.2013.00179. eCollection 2013.
• [12] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [13] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] 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.