Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIU8JWD)

• DOT Name: Reticulocalbin-2 (RCN2)
• Synonyms: Calcium-binding protein ERC-55; E6-binding protein; E6BP
• Gene Name: RCN2
• Related Disease:
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Absence epilepsy
  Arteriosclerosis
  Atherosclerosis
  Hepatocellular carcinoma
  High blood pressure
  Colorectal carcinoma
  Neoplasm
• UniProt ID: RCN2_HUMAN
• Pfam ID: PF13202 ; PF13499
• Sequence:
  MRLGPRTAALGLLLLCAAAAGAGKAEELHYPLGERRSDYDREALLGVQEDVDEYVKLGHE
  EQQKRLQAIIKKIDLDSDGFLTESELSSWIQMSFKHYAMQEAKQQFVEYDKNSDDTVTWD
  EYNIQMYDRVIDFDENTALDDAEEESFRKLHLKDKKRFEKANQDSGPGLSLEEFIAFEHP
  EEVDYMTEFVIQEALEEHDKNGDGFVSLEEFLGDYRWDPTANEDPEWILVEKDRFVNDYD
  KDNDGRLDPQELLPWVVPNNQGIAQEEALHLIDEMDLNGDKKLSEEEILENPDLFLTSEA
  TDYGRQLHDDYFYHDEL
• Function: Not known. Binds calcium.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Absence epilepsy	DISJPOUD	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Reticulocalbin-2 (RCN2).	[7]

17 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 Reticulocalbin-2 (RCN2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Reticulocalbin-2 (RCN2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Reticulocalbin-2 (RCN2).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Reticulocalbin-2 (RCN2).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Reticulocalbin-2 (RCN2).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Reticulocalbin-2 (RCN2).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Reticulocalbin-2 (RCN2).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Reticulocalbin-2 (RCN2).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Reticulocalbin-2 (RCN2).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Reticulocalbin-2 (RCN2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Reticulocalbin-2 (RCN2).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Reticulocalbin-2 (RCN2).	[19]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Reticulocalbin-2 (RCN2).	[19]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Reticulocalbin-2 (RCN2).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Reticulocalbin-2 (RCN2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Reticulocalbin-2 (RCN2).	[22]
1,4-Dithiothreitol	DMIFOXE	Investigative	1,4-Dithiothreitol increases the expression of Reticulocalbin-2 (RCN2).	[19]

References

• [1] Reticulocalbin 2 enhances osteogenic differentiation of human vascular smooth muscle cells in diabetic conditions.Life Sci. 2019 Sep 15;233:116746. doi: 10.1016/j.lfs.2019.116746. Epub 2019 Aug 9.
• [2] Gene expression analysis in absence epilepsy using a monozygotic twin design.Epilepsia. 2008 Sep;49(9):1546-54. doi: 10.1111/j.1528-1167.2008.01630.x. Epub 2008 Apr 24.
• [3] Loss of reticulocalbin 2 lowers blood pressure and restrains ANG II-induced hypertension in vivo.Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1141-F1150. doi: 10.1152/ajprenal.00567.2018. Epub 2019 Apr 3.
• [4] Reticulocalbin-2 enhances hepatocellular carcinoma proliferation via modulating the EGFR-ERK pathway.Oncogene. 2017 Nov 30;36(48):6747-6748. doi: 10.1038/onc.2017.366.
• [5] Downregulation of microRNA?83?p inhibits the proliferation and invasion of colorectal cancer cells by inactivating the reticulocalbin?/Wnt/catenin signaling pathway.Mol Med Rep. 2019 May;19(5):4475-4483. doi: 10.3892/mmr.2019.10059. Epub 2019 Mar 19.
• [6] Reticulocalbin 2 correlates with recurrence and prognosis in colorectal cancer.Am J Cancer Res. 2017 Nov 1;7(11):2169-2179. eCollection 2017.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [13] 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.
• [14] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.
• [19] Proteomic signatures in thapsigargin-treated hepatoma cells. Chem Res Toxicol. 2011 Aug 15;24(8):1215-22. doi: 10.1021/tx200109y. Epub 2011 Jul 1.
• [20] Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
• [21] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [22] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.