Details of Drug Off-Target (DOT)

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

• DOT Name: Calcipressin-2 (RCAN2)
• Synonyms: Down syndrome candidate region 1-like 1; Myocyte-enriched calcineurin-interacting protein 2; MCIP2; Regulator of calcineurin 2; Thyroid hormone-responsive protein ZAKI-4
• Gene Name: RCAN2
• Related Disease:
  Gastric cancer
  Neoplasm
  Obesity
  Stomach cancer
• UniProt ID: RCAN2_HUMAN
• Pfam ID: PF04847
• Sequence:
  MPAPSMDCDVSTLVACVVDVEVFTNQEVKEKFEGLFRTYDDCVTFQLFKSFRRVRINFSN
  PKSAARARIELHETQFRGKKLKLYFAQVQTPETDGDKLHLAPPQPAKQFLISPPSSPPVG
  WQPINDATPVLNYDLLYAVAKLGPGEKYELHAGTESTPSVVVHVCDSDIEEEEDPKTSPK
  PKIIQTRRPGLPPSVSN
• Function: Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development.
• Tissue Specificity: Expressed in fibroblasts, heart, brain, liver, and skeletal muscle but not in placenta, lung, kidney and pancreas.
• KEGG Pathway: Thyroid hormone sig.ling pathway (hsa04919)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]

2 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 Calcipressin-2 (RCAN2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Calcipressin-2 (RCAN2).	[11]

10 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 Calcipressin-2 (RCAN2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Calcipressin-2 (RCAN2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcipressin-2 (RCAN2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calcipressin-2 (RCAN2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Calcipressin-2 (RCAN2).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Calcipressin-2 (RCAN2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Calcipressin-2 (RCAN2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcipressin-2 (RCAN2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcipressin-2 (RCAN2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Calcipressin-2 (RCAN2).	[14]

References

• [1] Clinicopathological significance of RCAN2 production in gastric carcinoma.Histopathology. 2019 Feb;74(3):430-442. doi: 10.1111/his.13764.
• [2] Rcan2 and estradiol independently regulate body weight in female mice.Oncotarget. 2017 Jul 18;8(29):48098-48109. doi: 10.18632/oncotarget.18259.
• [3] 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.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.