Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM7YVIE)

• DOT Name: Receptor expression-enhancing protein 3 (REEP3)
• Gene Name: REEP3
• Related Disease:
  Atrial fibrillation
  Autism
  Familial atrial fibrillation
  Juvenile idiopathic arthritis
  Neuroblastoma
• UniProt ID: REEP3_HUMAN
• Pfam ID: PF03134
• Sequence:
  MVSWMISRAVVLVFGMLYPAYYSYKAVKTKNVKEYVRWMMYWIVFALYTVIETVADQTVA
  WFPLYYELKIAFVIWLLSPYTKGASLIYRKFLHPLLSSKEREIDDYIVQAKERGYETMVN
  FGRQGLNLAATAAVTAAVKSQGAITERLRSFSMHDLTTIQGDEPVGQRPYQPLPEAKKKS
  KPAPSESAGYGIPLKDGDEKTDEEAEGPYSDNEMLTHKGLRRSQSMKSVKTTKGRKEVRY
  GSLKYKVKKRPQVYF
• 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.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[1]
Juvenile idiopathic arthritis	DISQZGBV	Limited	Genetic Variation	[3]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[4]

8 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 Receptor expression-enhancing protein 3 (REEP3).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Receptor expression-enhancing protein 3 (REEP3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Receptor expression-enhancing protein 3 (REEP3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Receptor expression-enhancing protein 3 (REEP3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Receptor expression-enhancing protein 3 (REEP3).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Receptor expression-enhancing protein 3 (REEP3).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Receptor expression-enhancing protein 3 (REEP3).	[12]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Receptor expression-enhancing protein 3 (REEP3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Receptor expression-enhancing protein 3 (REEP3).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Receptor expression-enhancing protein 3 (REEP3).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Receptor expression-enhancing protein 3 (REEP3).	[13]

References

• [1] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [2] Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism.Eur J Hum Genet. 2007 Apr;15(4):422-31. doi: 10.1038/sj.ejhg.5201785. Epub 2007 Feb 7.
• [3] The DNA methylation landscape of CD4(+) T cells in oligoarticular juvenile idiopathic arthritis.J Autoimmun. 2018 Jan;86:29-38. doi: 10.1016/j.jaut.2017.09.010. Epub 2017 Sep 29.
• [4] Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder.Nat Commun. 2017 Oct 17;8(1):774. doi: 10.1038/s41467-017-00831-x.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] 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.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [12] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [13] 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.