Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ8LZGQ)

• DOT Name: Receptor expression-enhancing protein 4 (REEP4)
• Gene Name: REEP4
• UniProt ID: REEP4_HUMAN
• Pfam ID: PF03134
• Sequence:
  MVSWMICRLVVLVFGMLCPAYASYKAVKTKNIREYVRWMMYWIVFALFMAAEIVTDIFIS
  WFPFYYEIKMAFVLWLLSPYTKGASLLYRKFVHPSLSRHEKEIDAYIVQAKERSYETVLS
  FGKRGLNIAASAAVQAATKSQGALAGRLRSFSMQDLRSISDAPAPAYHDPLYLEDQVSHR
  RPPIGYRAGGLQDSDTEDECWSDTEAVPRAPARPREKPLIRSQSLRVVKRKPPVREGTSR
  SLKVRTRKKTVPSDVDS
• Function: Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes.
• Tissue Specificity: Expressed in circumvallate papillae and testis.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Receptor expression-enhancing protein 4 (REEP4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Receptor expression-enhancing protein 4 (REEP4).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Receptor expression-enhancing protein 4 (REEP4).	[10]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Receptor expression-enhancing protein 4 (REEP4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Receptor expression-enhancing protein 4 (REEP4).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Receptor expression-enhancing protein 4 (REEP4).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Receptor expression-enhancing protein 4 (REEP4).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Receptor expression-enhancing protein 4 (REEP4).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Receptor expression-enhancing protein 4 (REEP4).	[13]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] 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.