Details of Drug Off-Target (DOT)

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

• DOT Name: Protein RER1 (RER1)
• Gene Name: RER1
• Related Disease:
  Alzheimer disease
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type 1A
  Parkinson disease
  Neoplasm
  Pancreatic cancer
• UniProt ID: RER1_HUMAN
• Pfam ID: PF03248
• Sequence:
  MSEGDSVGESVHGKPSVVYRFFTRLGQIYQSWLDKSTPYTAVRWVVTLGLSFVYMIRVYL
  LQGWYIVTYALGIYHLNLFIAFLSPKVDPSLMEDSDDGPSLPTKQNEEFRPFIRRLPEFK
  FWHAATKGILVAMVCTFFDAFNVPVFWPILVMYFIMLFCITMKRQIKHMIKYRYIPFTHG
  KRRYRGKEDAGKAFAS
• Function: Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[2]
Charcot-Marie-Tooth disease type 1A	DISSRZG7	Strong	Genetic Variation	[2]
Parkinson disease	DISQVHKL	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Biomarker	[3]

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 Protein RER1 (RER1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein RER1 (RER1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein RER1 (RER1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein RER1 (RER1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein RER1 (RER1).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein RER1 (RER1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein RER1 (RER1).	[13]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein RER1 (RER1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Protein RER1 (RER1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein RER1 (RER1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein RER1 (RER1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein RER1 (RER1).	[12]

References

• [1] The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome.PLoS One. 2017 Sep 6;12(9):e0184262. doi: 10.1371/journal.pone.0184262. eCollection 2017.
• [2] Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease.Sci Rep. 2014 Nov 11;4:6992. doi: 10.1038/srep06992.
• [3] RER1 enhances carcinogenesis and stemness of pancreatic cancer under hypoxic environment.J Exp Clin Cancer Res. 2019 Jan 10;38(1):15. doi: 10.1186/s13046-018-0986-x.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [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] 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.
• [9] 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.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.