Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWV8DXJ)

DOT Name Syncytin-1 (ERVW-1)
Synonyms Endogenous retrovirus group W member 1; Env-W; Envelope polyprotein gPr73; Enverin; HERV-7q Envelope protein; HERV-W envelope protein; HERV-W_7q21.2 provirus ancestral Env polyprotein; Syncytin
Gene Name ERVW-1
Related Disease
Acute erythroid leukemia ( )
Ovarian cancer ( )
T-cell leukaemia ( )
Acquired immune deficiency syndrome ( )
Acute myelogenous leukaemia ( )
Adult T-cell leukemia/lymphoma ( )
Anemia ( )
Bipolar disorder ( )
Breast neoplasm ( )
Choriocarcinoma ( )
Dementia ( )
Endometriosis ( )
Glioblastoma multiforme ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
HIV infectious disease ( )
Immunodeficiency ( )
Influenza ( )
Lichen planus ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Multiple sclerosis ( )
Neoplasm ( )
Nervous system disease ( )
Neuroblastoma ( )
Primary cutaneous T-cell lymphoma ( )
Rabies ( )
Schizophrenia ( )
Seminoma ( )
Systemic lupus erythematosus ( )
Zika virus infection ( )
Adult lymphoma ( )
Eclampsia ( )
Fetal growth restriction ( )
Lung adenocarcinoma ( )
Neuralgia ( )
Pediatric lymphoma ( )
Pre-eclampsia ( )
Advanced cancer ( )
Dengue ( )
Ebola virus infection ( )
Endometrial carcinoma ( )
Hepatitis A virus infection ( )
Herpes simplex infection ( )
UniProt ID
SYCY1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5HA6; 6RX1
Pfam ID
PF00429
Sequence
MALPYHIFLFTVLLPSFTLTAPPPCRCMTSSSPYQEFLWRMQRPGNIDAPSYRSLSKGTP
TFTAHTHMPRNCYHSATLCMHANTHYWTGKMINPSCPGGLGVTVCWTYFTQTGMSDGGGV
QDQAREKHVKEVISQLTRVHGTSSPYKGLDLSKLHETLRTHTRLVSLFNTTLTGLHEVSA
QNPTNCWICLPLNFRPYVSIPVPEQWNNFSTEINTTSVLVGPLVSNLEITHTSNLTCVKF
SNTTYTTNSQCIRWVTPPTQIVCLPSGIFFVCGTSAYRCLNGSSESMCFLSFLVPPMTIY
TEQDLYSYVISKPRNKRVPILPFVIGAGVLGALGTGIGGITTSTQFYYKLSQELNGDMER
VADSLVTLQDQLNSLAAVVLQNRRALDLLTAERGGTCLFLGEECCYYVNQSGIVTEKVKE
IRDRIQRRAEELRNTGPWGLLSQWMPWILPFLGPLAAIILLLLFGPCIFNLLVNFVSSRI
EAVKLQMEPKMQSKTKIYRRPLDRPASPRSDVNDIKGTPPEEISAAQPLLRPNSAGSS
Function
This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. May induce fusion through binding of SLC1A4 and SLC1A5 ; Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes.
Tissue Specificity
Expressed at higher level in placental syncytiotrophoblast. Expressed at intermediate level in testis. Seems also to be found at low level in adrenal tissue, bone marrow, breast, colon, kidney, ovary, prostate, skin, spleen, thymus, thyroid, brain and trachea. Both mRNA and protein levels are significantly increased in the brain of individuals with multiple sclerosis, particularly in astrocytes and microglia.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute erythroid leukemia DISZFC1O Definitive Biomarker [1]
Ovarian cancer DISZJHAP Definitive Altered Expression [2]
T-cell leukaemia DISJ6YIF Definitive Biomarker [3]
Acquired immune deficiency syndrome DISL5UOX Strong Genetic Variation [4]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [5]
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [6]
Anemia DISTVL0C Strong Biomarker [7]
Bipolar disorder DISAM7J2 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Choriocarcinoma DISDBVNL Strong Biomarker [10]
Dementia DISXL1WY Strong Genetic Variation [11]
Endometriosis DISX1AG8 Strong Altered Expression [12]
Glioblastoma multiforme DISK8246 Strong Biomarker [13]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [14]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [15]
HIV infectious disease DISO97HC Strong Biomarker [16]
Immunodeficiency DIS093I0 Strong Biomarker [17]
Influenza DIS3PNU3 Strong Biomarker [18]
Lichen planus DISRPMMS Strong Biomarker [19]
Lung cancer DISCM4YA Strong Biomarker [20]
Lung carcinoma DISTR26C Strong Biomarker [20]
Lymphoma DISN6V4S Strong Biomarker [21]
Multiple sclerosis DISB2WZI Strong Biomarker [22]
Neoplasm DISZKGEW Strong Biomarker [23]
Nervous system disease DISJ7GGT Strong Genetic Variation [24]
Neuroblastoma DISVZBI4 Strong Altered Expression [25]
Primary cutaneous T-cell lymphoma DIS35WVW Strong Altered Expression [26]
Rabies DISSC4V5 Strong Biomarker [27]
Schizophrenia DISSRV2N Strong Biomarker [22]
Seminoma DIS3J8LJ Strong Altered Expression [28]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [29]
Zika virus infection DISQUCTY Strong Biomarker [30]
Adult lymphoma DISK8IZR moderate Biomarker [21]
Eclampsia DISWPO8U moderate Altered Expression [31]
Fetal growth restriction DIS5WEJ5 moderate Biomarker [32]
Lung adenocarcinoma DISD51WR moderate Altered Expression [33]
Neuralgia DISWO58J moderate Biomarker [34]
Pediatric lymphoma DIS51BK2 moderate Biomarker [21]
Pre-eclampsia DISY7Q29 moderate Altered Expression [31]
Advanced cancer DISAT1Z9 Limited Altered Expression [35]
Dengue DISKH221 Limited Biomarker [36]
Ebola virus infection DISJAVM1 Limited Biomarker [37]
Endometrial carcinoma DISXR5CY Limited Altered Expression [35]
Hepatitis A virus infection DISUMFQV Limited Genetic Variation [15]
Herpes simplex infection DISL1SAV Limited Biomarker [38]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Syncytin-1 (ERVW-1). [39]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Syncytin-1 (ERVW-1). [40]
Marinol DM70IK5 Approved Marinol decreases the expression of Syncytin-1 (ERVW-1). [41]
Progesterone DMUY35B Approved Progesterone increases the expression of Syncytin-1 (ERVW-1). [42]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Syncytin-1 (ERVW-1). [43]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Syncytin-1 (ERVW-1). [40]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Syncytin-1 (ERVW-1). [44]
Forskolin DM6ITNG Investigative Forskolin increases the expression of Syncytin-1 (ERVW-1). [40]
Anandamide DMCKH3P Investigative Anandamide decreases the expression of Syncytin-1 (ERVW-1). [45]
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⏷ Show the Full List of 9 Drug(s)

References

1 Oncogene cooperativity in Friend erythroleukemia: erythropoietin receptor activation by the env gene of SFFV leads to transcriptional upregulation of PU.1, independent of SFFV proviral insertion.Oncogene. 2002 Feb 14;21(8):1272-84. doi: 10.1038/sj.onc.1205183.
2 Promoter Hypermethylation and Decreased Expression of Syncytin-1 in Pancreatic Adenocarcinomas.PLoS One. 2015 Jul 31;10(7):e0134412. doi: 10.1371/journal.pone.0134412. eCollection 2015.
3 HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 alleles predispose to adult T cell leukemia: the limited recognition of HTLV type 1 tax peptide anchor motifs and epitopes to generate anti-HTLV type 1 tax CD8(+) cytotoxic T lymphocytes.AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1047-61. doi: 10.1089/088922201300343735.
4 Loci polymorphisms of the APOBEC3G gene in HIV type 1-infected Brazilians.AIDS Res Hum Retroviruses. 2011 Feb;27(2):137-41. doi: 10.1089/aid.2010.0146. Epub 2010 Sep 28.
5 Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines.Mutagenesis. 2016 Nov;31(6):695-702. doi: 10.1093/mutage/gew043. Epub 2016 Aug 30.
6 Antibodies to the envelope glycoprotein of human T cell leukemia virus type 1 robustly activate cell-mediated cytotoxic responses and directly neutralize viral infectivity at multiple steps of the entry process.J Immunol. 2011 Jul 1;187(1):361-71. doi: 10.4049/jimmunol.1100070. Epub 2011 Jun 6.
7 A putative cell surface receptor for anemia-inducing feline leukemia virus subgroup C is a member of a transporter superfamily.J Virol. 1999 Aug;73(8):6500-5. doi: 10.1128/JVI.73.8.6500-6505.1999.
8 Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.Transl Psychiatry. 2012 Dec 4;2(12):e201. doi: 10.1038/tp.2012.125.
9 No evidence of mammary tumor virus env gene-like sequences among Iranian women with breast cancer.Intervirology. 2014;57(6):353-6. doi: 10.1159/000366280. Epub 2014 Oct 15.
10 Reduced syncytin-1 expression in choriocarcinoma BeWo cells activates the calpain1-AIF-mediated apoptosis, implication for preeclampsia.Cell Mol Life Sci. 2014 Aug;71(16):3151-64. doi: 10.1007/s00018-013-1533-8. Epub 2014 Jan 12.
11 A machine learning approach for identifying amino acid signatures in the HIV env gene predictive of dementia.PLoS One. 2012;7(11):e49538. doi: 10.1371/journal.pone.0049538. Epub 2012 Nov 14.
12 Hypomethylation and activation of syncytin-1 gene in endometriotic tissue.Curr Pharm Des. 2014;20(11):1786-95. doi: 10.2174/13816128113199990540.
13 HIV-1 Envelope Protein gp120 Promotes Proliferation and the Activation of Glycolysis in Glioma Cell.Cancers (Basel). 2018 Sep 1;10(9):301. doi: 10.3390/cancers10090301.
14 Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses.Virol Sin. 2018 Dec;33(6):502-514. doi: 10.1007/s12250-018-0074-6. Epub 2018 Dec 19.
15 Syntenin regulates hepatitis C virus sensitivity to neutralizing antibody by promoting E2 secretion through exosomes.J Hepatol. 2019 Jul;71(1):52-61. doi: 10.1016/j.jhep.2019.03.006. Epub 2019 Mar 15.
16 HIV-1 gp120 envelope glycoprotein determinants for cytokine burst in human monocytes.PLoS One. 2017 Mar 27;12(3):e0174550. doi: 10.1371/journal.pone.0174550. eCollection 2017.
17 Contribution of the gp120 V3 loop to envelope glycoprotein trimer stability in primate immunodeficiency viruses.Virology. 2018 Aug;521:158-168. doi: 10.1016/j.virol.2018.06.005. Epub 2018 Jun 21.
18 Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers.Cell. 2018 Aug 9;174(4):926-937.e12. doi: 10.1016/j.cell.2018.05.050. Epub 2018 Jun 28.
19 Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus.Arch Dermatol Res. 2015 Apr;307(3):259-64. doi: 10.1007/s00403-014-1524-0. Epub 2014 Nov 11.
20 Human endogenous retrovirus env genes: Potential blood biomarkers in lung cancer.Microb Pathog. 2018 Feb;115:189-193. doi: 10.1016/j.micpath.2017.12.040. Epub 2017 Dec 20.
21 Expression of syncytin in leukemia and lymphoma cells.Leuk Res. 2010 Sep;34(9):1195-202. doi: 10.1016/j.leukres.2010.03.016. Epub 2010 Apr 2.
22 HERV-W env regulates calcium influx via activating TRPC3 channel together with depressing DISC1 in human neuroblastoma cells.J Neurovirol. 2019 Feb;25(1):101-113. doi: 10.1007/s13365-018-0692-7. Epub 2018 Nov 5.
23 Identification of Tumoricidal TCRs from Tumor-Infiltrating Lymphocytes by Single-Cell Analysis.Cancer Immunol Res. 2018 Apr;6(4):378-388. doi: 10.1158/2326-6066.CIR-17-0489. Epub 2018 Feb 23.
24 Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice.Sci Rep. 2019 Nov 20;9(1):17158. doi: 10.1038/s41598-019-53466-x.
25 Dynamic and selective HERV RNA expression in neuroblastoma cells subjected to variation in oxygen tension and demethylation.APMIS. 2016 Jan-Feb;124(1-2):140-9. doi: 10.1111/apm.12494.
26 Expression of human endogenous retrovirus-w including syncytin-1 in cutaneous T-cell lymphoma.PLoS One. 2013 Oct 1;8(10):e76281. doi: 10.1371/journal.pone.0076281. eCollection 2013.
27 Single domain antibody multimers confer protection against rabies infection.PLoS One. 2013 Aug 20;8(8):e71383. doi: 10.1371/journal.pone.0071383. eCollection 2013.
28 DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas.Retrovirology. 2017 Mar 17;14(1):20. doi: 10.1186/s12977-017-0342-9.
29 The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV.Immunity. 2019 Feb 19;50(2):334-347.e9. doi: 10.1016/j.immuni.2018.12.022. Epub 2019 Jan 29.
30 Optimization of Zika virus envelope protein production for ELISA and correlation of antibody titers with virus neutralization in Mexican patients from an arbovirus endemic region.Virol J. 2018 Dec 27;15(1):193. doi: 10.1186/s12985-018-1104-6.
31 Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia.Biochim Biophys Acta. 2003 May 20;1638(1):63-71. doi: 10.1016/s0925-4439(03)00043-7.
32 Intrauterine growth retardation-associated syncytin b hypermethylation in maternal rat blood revealed by DNA methylation array analysis.Pediatr Res. 2017 Oct;82(4):704-711. doi: 10.1038/pr.2017.137. Epub 2017 Jul 5.
33 Early Steps of Jaagsiekte Sheep Retrovirus-Mediated Cell Transformation Involve the Interaction between Env and the RALBP1 Cellular Protein.J Virol. 2015 Aug;89(16):8462-73. doi: 10.1128/JVI.00590-15. Epub 2015 Jun 3.
34 P2Y(12) shRNA treatment relieved HIV gp120-induced neuropathic pain in rats.Neurochem Int. 2018 Jan;112:259-266. doi: 10.1016/j.neuint.2017.08.006. Epub 2017 Aug 18.
35 Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma.Onco Targets Ther. 2018 Dec 17;12:31-40. doi: 10.2147/OTT.S191041. eCollection 2019.
36 Engineered Dengue Virus Domain III Proteins Elicit Cross-Neutralizing Antibody Responses in Mice.J Virol. 2018 Aug 29;92(18):e01023-18. doi: 10.1128/JVI.01023-18. Print 2018 Sep 15.
37 Molecular modelling studies on adamantane-based Ebola virus GP-1 inhibitors using docking, pharmacophore and 3D-QSAR.SAR QSAR Environ Res. 2019 Mar;30(3):161-180. doi: 10.1080/1062936X.2019.1573377. Epub 2019 Feb 20.
38 Role of Herpes Simplex Envelope Glycoprotein B and Toll-Like Receptor 2 in Ocular Inflammation: An ex vivo Organotypic Rabbit Corneal Model.Viruses. 2019 Sep 4;11(9):819. doi: 10.3390/v11090819.
39 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
40 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.
41 The psychoactive compound of Cannabis sativa, (9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover. Toxicology. 2015 Aug 6;334:94-103. doi: 10.1016/j.tox.2015.06.005. Epub 2015 Jun 9.
42 Role of HERV-W syncytin-1 in placentation and maintenance of human pregnancy. Appl Immunohistochem Mol Morphol. 2009 Jul;17(4):319-28. doi: 10.1097/PAI.0b013e31819640f9.
43 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
44 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
45 Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis. Pharmacol Res. 2019 Mar;141:331-342. doi: 10.1016/j.phrs.2019.01.002. Epub 2019 Jan 2.