Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU22IKI)

• DOT Name: Immunoglobulin superfamily member 8 (IGSF8)
• Synonyms: IgSF8; CD81 partner 3; Glu-Trp-Ile EWI motif-containing protein 2; EWI-2; Keratinocytes-associated transmembrane protein 4; KCT-4; LIR-D1; Prostaglandin regulatory-like protein; PGRL; CD antigen CD316
• Gene Name: IGSF8
• Related Disease:
  Adult glioblastoma
  Endometriosis
  Glioblastoma multiforme
  Hepatitis C virus infection
  Neoplasm
  Prostate neoplasm
  Melanoma
  Metastatic melanoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: IGSF8_HUMAN
• Pfam ID: PF07686
• Sequence:
  MGALRPTLLPPSLPLLLLLMLGMGCWAREVLVPEGPLYRVAGTAVSISCNVTGYEGPAQQ
  NFEWFLYRPEAPDTALGIVSTKDTQFSYAVFKSRVVAGEVQVQRLQGDAVVLKIARLQAQ
  DAGIYECHTPSTDTRYLGSYSGKVELRVLPDVLQVSAAPPGPRGRQAPTSPPRMTVHEGQ
  ELALGCLARTSTQKHTHLAVSFGRSVPEAPVGRSTLQEVVGIRSDLAVEAGAPYAERLAA
  GELRLGKEGTDRYRMVVGGAQAGDAGTYHCTAAEWIQDPDGSWAQIAEKRAVLAHVDVQT
  LSSQLAVTVGPGERRIGPGEPLELLCNVSGALPPAGRHAAYSVGWEMAPAGAPGPGRLVA
  QLDTEGVGSLGPGYEGRHIAMEKVASRTYRLRLEAARPGDAGTYRCLAKAYVRGSGTRLR
  EAASARSRPLPVHVREEGVVLEAVAWLAGGTVYRGETASLLCNISVRGGPPGLRLAASWW
  VERPEDGELSSVPAQLVGGVGQDGVAELGVRPGGGPVSVELVGPRSHRLRLHSLGPEDEG
  VYHCAPSAWVQHADYSWYQAGSARSGPVTVYPYMHALDTLFVPLLVGTGVALVTGATVLG
  TITCCFMKRLRKR
• Function: May play a key role in diverse functions ascribed to CD81 and CD9 such as oocytes fertilization or hepatitis C virus function. May regulate proliferation and differentiation of keratinocytes. May be a negative regulator of cell motility: suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. May also play a role on integrin-dependent morphology and motility functions. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.
• Tissue Specificity: Expressed in brain, kidney, testis, liver and placenta with moderate expression in all other tissues. Detected on a majority of B-cells, T-cells, and natural killer cells but not on monocytes, polynuclear cells and platelets.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Endometriosis	DISX1AG8	Strong	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]
Melanoma	DIS1RRCY	Limited	Biomarker	[5]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[5]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[6]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[6]

11 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 Immunoglobulin superfamily member 8 (IGSF8).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[14]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Immunoglobulin superfamily member 8 (IGSF8).	[16]

References

• [1] Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo.Neoplasia. 2009 Jan;11(1):77-86, 4p following 86. doi: 10.1593/neo.81180.
• [2] Differential expression of EWI-2 in endometriosis, its functional role and underlying molecular mechanisms.J Obstet Gynaecol Res. 2017 Jul;43(7):1180-1188. doi: 10.1111/jog.13333. Epub 2017 May 22.
• [3] The CD81 partner EWI-2wint inhibits hepatitis C virus entry.PLoS One. 2008 Apr 2;3(4):e1866. doi: 10.1371/journal.pone.0001866.
• [4] EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.Cancer Res. 2003 May 15;63(10):2665-74.
• [5] EWI-2 negatively regulates TGF- signaling leading to altered melanoma growth and metastasis.Cell Res. 2015 Mar;25(3):370-85. doi: 10.1038/cr.2015.17. Epub 2015 Feb 6.
• [6] Identification of novel genes that regulate androgen receptor signaling and growth of androgen-deprived prostate cancer cells.Oncotarget. 2015 May 30;6(15):13088-104. doi: 10.18632/oncotarget.3743.
• [7] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [8] 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.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] 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.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study. BMC Med Genomics. 2011 Mar 31;4:29. doi: 10.1186/1755-8794-4-29.
• [13] 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.
• [14] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [15] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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.