Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPCRA5O)

• DOT Name: Receptor expression-enhancing protein 2 (REEP2)
• Gene Name: REEP2
• Related Disease:
  Vascular purpura
  Hereditary spastic paraplegia 72
  Hereditary spastic paraplegia
• UniProt ID: REEP2_HUMAN
• Pfam ID: PF03134
• Sequence:
  MVSWIISRLVVLIFGTLYPAYSSYKAVKTKNVKEYVKWMMYWIVFAFFTTAETLTDIVLS
  WFPFYFELKIAFVIWLLSPYTKGSSVLYRKFVHPTLSNKEKEIDEYITQARDKSYETMMR
  VGKRGLNLAANAAVTAAAKGVLSEKLRSFSMQDLTLIRDEDALPLQRPDGRLRPSPGSLL
  DTIEDLGDDPALSLRSSTNPADSRTEASEDDMGDKAPKRAKPIKKAPKAEPLASKTLKTR
  PKKKTSGGGDSA
• Function: Required for endoplasmic reticulum (ER) network formation, shaping and remodeling. May enhance the cell surface expression of odorant receptors.
• Tissue Specificity: Detected in brain, heart and skeletal muscle, and at low levels in placenta, kidney and pancreas . Expressed in circumvallate papillae .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vascular purpura	DIS6ZZMF	Definitive	Genetic Variation	[1]
Hereditary spastic paraplegia 72	DIS0N7IU	Strong	Autosomal dominant	[2]
Hereditary spastic paraplegia	DISGZQV1	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Receptor expression-enhancing protein 2 (REEP2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Receptor expression-enhancing protein 2 (REEP2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Receptor expression-enhancing protein 2 (REEP2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Receptor expression-enhancing protein 2 (REEP2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Receptor expression-enhancing protein 2 (REEP2).	[8]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Receptor expression-enhancing protein 2 (REEP2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Receptor expression-enhancing protein 2 (REEP2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Receptor expression-enhancing protein 2 (REEP2).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Receptor expression-enhancing protein 2 (REEP2).	[12]

References

• [1] Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. Am J Hum Genet. 2014 Feb 6;94(2):268-77. doi: 10.1016/j.ajhg.2013.12.005. Epub 2014 Jan 2.
• [2] [Dumping syndrome and reactive hypoglycemia in a patient following esophagoplasty and methods of treatment]. Zentralbl Chir. 1987;112(5):320-6.
• [3] Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.Rev Neurol (Paris). 2015 Jun-Jul;171(6-7):505-30. doi: 10.1016/j.neurol.2015.02.017. Epub 2015 May 23.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [9] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.