Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTS3CQA)

• DOT Name: Calcipressin-3 (RCAN3)
• Synonyms: Down syndrome candidate region 1-like protein 2; Myocyte-enriched calcineurin-interacting protein 3; MCIP3; Regulator of calcineurin 3
• Gene Name: RCAN3
• Related Disease:
  Arthritis
  Neoplasm
  Rheumatoid arthritis
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
• UniProt ID: RCAN3_HUMAN
• Pfam ID: PF04847
• Sequence:
  MLRDTMKSWNDSQSDLCSTDQEEEEEMIFGENEDDLDEMMDLSDLPTSLFACSVHEAVFE
  AREQKERFEALFTIYDDQVTFQLFKSFRRVRINFSKPEAAARARIELHETDFNGQKLKLY
  FAQVQMSGEVRDKSYLLPPQPVKQFLISPPASPPVGWKQSEDAMPVINYDLLCAVSKLGP
  GEKYELHAGTESTPSVVVHVCESETEEEEETKNPKQKIAQTRRPDPPTAALNEPQTFDCA
  L
• 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: Highest expression in heart, skeletal muscle kidney, liver and peripheral blood leukocytes. Lower expression in all other tissues.
• Reactome Pathway: SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[2]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calcipressin-3 (RCAN3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcipressin-3 (RCAN3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calcipressin-3 (RCAN3).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calcipressin-3 (RCAN3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcipressin-3 (RCAN3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calcipressin-3 (RCAN3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Calcipressin-3 (RCAN3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Calcipressin-3 (RCAN3).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Calcipressin-3 (RCAN3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Calcipressin-3 (RCAN3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Calcipressin-3 (RCAN3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calcipressin-3 (RCAN3).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Calcipressin-3 (RCAN3).	[16]

References

• [1] Regulator of Calcineurin 3 Ameliorates Autoimmune Arthritis by Suppressing Th17 Cell Differentiation.Am J Pathol. 2017 Sep;187(9):2034-2045. doi: 10.1016/j.ajpath.2017.05.008. Epub 2017 Jul 10.
• [2] A novel role for an RCAN3-derived peptide as a tumor suppressor in breast cancer.Carcinogenesis. 2015 Jul;36(7):792-9. doi: 10.1093/carcin/bgv056. Epub 2015 Apr 26.
• [3] A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2).Genomics. 2000 Mar 15;64(3):252-63. doi: 10.1006/geno.2000.6127.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.