Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JBGAG)

• DOT Name: Reticulocalbin-1 (RCN1)
• Gene Name: RCN1
• Related Disease:
  Carcinoma
  Advanced cancer
  Dementia
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Undifferentiated carcinoma
  Periodontitis
• UniProt ID: RCN1_HUMAN
• Pfam ID: PF13202 ; PF13499
• Sequence:
  MARGGRGRRLGLALGLLLALVLAPRVLRAKPTVRKERVVRPDSELGERPPEDNQSFQYDH
  EAFLGKEDSKTFDQLTPDESKERLGKIVDRIDNDGDGFVTTEELKTWIKRVQKRYIFDNV
  AKVWKDYDRDKDDKISWEEYKQATYGYYLGNPAEFHDSSDHHTFKKMLPRDERRFKAADL
  NGDLTATREEFTAFLHPEEFEHMKEIVVLETLEDIDKNGDGFVDQDEYIADMFSHEENGP
  EPDWVLSEREQFNEFRDLNKDGKLDKDEIRHWILPQDYDHAQAEARHLVYESDKNKDEKL
  TKEEILENWNMFVGSQATNYGEDLTKNHDEL
• Function: May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Dementia	DISXL1WY	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Periodontitis	DISI9JOI	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Reticulocalbin-1 (RCN1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Reticulocalbin-1 (RCN1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Reticulocalbin-1 (RCN1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Reticulocalbin-1 (RCN1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Reticulocalbin-1 (RCN1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Reticulocalbin-1 (RCN1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Reticulocalbin-1 (RCN1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Reticulocalbin-1 (RCN1).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Reticulocalbin-1 (RCN1).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Reticulocalbin-1 (RCN1).	[16]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Reticulocalbin-1 (RCN1).	[17]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Reticulocalbin-1 (RCN1).	[18]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Reticulocalbin-1 (RCN1).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Reticulocalbin-1 (RCN1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Reticulocalbin-1 (RCN1).	[22]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Reticulocalbin-1 (RCN1).	[23]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Reticulocalbin-1 (RCN1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Reticulocalbin-1 (RCN1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Reticulocalbin-1 (RCN1).	[24]

References

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• [2] Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.Cancer Sci. 2018 Apr;109(4):1147-1157. doi: 10.1111/cas.13541. Epub 2018 Mar 31.
• [3] Hydration Interventions for older people living in residential and nursing care homes: overview of the literature.Br Med Bull. 2019 Sep 19;131(1):71-79. doi: 10.1093/bmb/ldz027.
• [4] Irradiation of Epithelial Carcinoma Cells Upregulates Calcium-Binding Proteins That Promote Survival under Hypoxic Conditions.J Proteome Res. 2016 Dec 2;15(12):4258-4264. doi: 10.1021/acs.jproteome.6b00340. Epub 2016 Nov 10.
• [5] Overexpression of RCN1 correlates with poor prognosis and progression in non-small cell lung cancer.Hum Pathol. 2019 Jan;83:140-148. doi: 10.1016/j.humpath.2018.08.014. Epub 2018 Aug 30.
• [6] Loss of alveolar bone density in postmenopausal, osteopenic women is associated with circulating levels of gelatinases.J Periodontal Res. 2019 Oct;54(5):525-532. doi: 10.1111/jre.12656. Epub 2019 Apr 29.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [13] 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.
• [14] Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid. Cancer Chemother Pharmacol. 2008 Apr;61(5):791-802.
• [15] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [16] 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.
• [17] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [18] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [19] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [20] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [21] 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.
• [22] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [23] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [24] 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.
• [25] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.