Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0YQR22)

• DOT Name: Endosomal transmembrane epsin interactor 1 (ENTREP1)
• Synonyms: Endosomal transmembrane binding with epsin
• Gene Name: ENTREP1
• Related Disease: Schizophrenia
• UniProt ID: EREP1_HUMAN
• Sequence:
  MILLVNLFVLLSVVCVLLNLAGFILGCQGAQFVSSVPRCDLVDLGEGKICFCCEEFQPAK
  CTDKENALKLFPVQPCSAVHLLLKKVLFALCALNALTTTVCLVAAALRYLQIFATRRSCI
  DESQISAEEAEDHGRIPDPDDFVPPVPPPSYFATFYSCTPRMNRRMVGPDVIPLPHIYGA
  RIKGVEVFCPLDPPPPYEAVVSQMDQEQGSSFQMSEGSEAAVIPLDLGCTQVTQDGDIPN
  IPAEENASTSTPSSTLVRPIRSRRALPPLRTRSKSDPVLHPSEERAAPVLSCEAATQTER
  RLDLAAVTLRRGLRSRASRCRPRSLIDYKSYMDTKLLVARFLEQSSCTMTPDIHELVENI
  KSVLKSDEEHMEEAITSASFLEQIMAPLQPSTSRAHKLPSRRQPGLLHLQSCGDLHTFTP
  AGRPRAERRPRRVEAERPHSLIGVIRETVL
• Function: Functions as an activator of the E3 ubiquitin protein ligase ITCH in the ubiquitination of the CXCL12-activated CXCR4 receptor. Thereby, triggers CXCR4 endocytosis and desensitization, negatively regulating the CXCL12/CXCR4 signaling pathway.
• Tissue Specificity: Prominently expressed in muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	No Known	Unknown	[1]

14 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 Endosomal transmembrane epsin interactor 1 (ENTREP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Endosomal transmembrane epsin interactor 1 (ENTREP1).	[15]

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 Endosomal transmembrane epsin interactor 1 (ENTREP1).	[12]

References

• [1] Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. Am J Hum Genet. 2010 Jul 9;87(1):101-9. doi: 10.1016/j.ajhg.2010.05.011. Epub 2010 Jun 17.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] 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.
• [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] 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.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] 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.
• [13] 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.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.