Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY4FPO8)

• DOT Name: Receptor expression-enhancing protein 6 (REEP6)
• Synonyms: Polyposis locus protein 1-like 1
• Gene Name: REEP6
• Related Disease:
  Colon cancer
  Colon carcinoma
  Crohn disease
  Inflammatory bowel disease
  Neoplasm
  Ulcerative colitis
  Inherited retinal dystrophy
  Retinitis pigmentosa 77
  Retinitis pigmentosa
  Lung cancer
  Lung carcinoma
• UniProt ID: REEP6_HUMAN
• Pfam ID: PF03134
• Sequence:
  MDGLRQRVEHFLEQRNLVTEVLGALEAKTGVEKRYLAAGAVTLLSLYLLFGYGASLLCNL
  IGFVYPAYASIKAIESPSKDDDTVWLTYWVVYALFGLAEFFSDLLLSWFPFYYVGKCAFL
  LFCMAPRPWNGALMLYQRVVRPLFLRHHGAVDRIMNDLSGRALDAAAGITRNVLQVLARS
  RAGITPVAVAGPSTPLEADLKPSQTPQPKDK
• Function: Required for correct function and survival of retinal photoreceptors. Required for retinal development. In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis. May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane.
• Tissue Specificity: Expressed in circumvallate papillae and testis . Expressed in the retina. Isoform 1 is predominantly present in mature optic cups. Isoform 1 expression is confined to the cell body and inner segment of developing rod photoreceptor cells .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Definitive	Genetic Variation	[1]
Colon carcinoma	DISJYKUO	Definitive	Genetic Variation	[1]
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[1]
Inflammatory bowel disease	DISGN23E	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Ulcerative colitis	DIS8K27O	Definitive	Genetic Variation	[1]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[2]
Retinitis pigmentosa 77	DIS5X7WV	Strong	Autosomal recessive	[3]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[4]
Lung carcinoma	DISTR26C	Limited	Biomarker	[4]

1 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 6 (REEP6).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Receptor expression-enhancing protein 6 (REEP6).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Receptor expression-enhancing protein 6 (REEP6).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Receptor expression-enhancing protein 6 (REEP6).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Receptor expression-enhancing protein 6 (REEP6).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Receptor expression-enhancing protein 6 (REEP6).	[16]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Receptor expression-enhancing protein 6 (REEP6).	[17]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Receptor expression-enhancing protein 6 (REEP6).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Receptor expression-enhancing protein 6 (REEP6).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Receptor expression-enhancing protein 6 (REEP6).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Receptor expression-enhancing protein 6 (REEP6).	[25]

References

• [1] Polymorphisms of the apoptosis-associated gene DP1L1 (deleted in polyposis 1-like 1) in colon cancer and inflammatory bowel disease.J Cancer Res Clin Oncol. 2010 Jun;136(6):795-802. doi: 10.1007/s00432-009-0719-9. Epub 2009 Nov 19.
• [2] Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa. Am J Hum Genet. 2016 Dec 1;99(6):1305-1315. doi: 10.1016/j.ajhg.2016.10.008. Epub 2016 Nov 23.
• [3] Regulation of a novel isoform of Receptor Expression Enhancing Protein REEP6 in rod photoreceptors by bZIP transcription factor NRL. Hum Mol Genet. 2014 Aug 15;23(16):4260-71. doi: 10.1093/hmg/ddu143. Epub 2014 Apr 1.
• [4] The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression.Sci Rep. 2016 Dec 14;6:39041. doi: 10.1038/srep39041.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] 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.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] 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.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [17] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [18] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [19] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [20] 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.
• [21] 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.
• [22] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [23] 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.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] 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.