Details of Drug Off-Target (DOT)

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

• DOT Name: RNA 3'-terminal phosphate cyclase (RTCA)
• Synonyms: RNA cyclase; RNA-3'-phosphate cyclase; EC 6.5.1.4; RNA terminal phosphate cyclase domain-containing protein 1; RTC domain-containing protein 1
• Gene Name: RTCA
• Related Disease:
  Coronary heart disease
  OPTN-related open angle glaucoma
  Central diabetes insipidus
  Epilepsy
  Myocardial infarction
  Neoplasm
  Non-alcoholic fatty liver disease
  Stroke
  Advanced cancer
  Autoimmune disease
  Clear cell renal carcinoma
  Connective tissue disorder
  Renal cell carcinoma
  Scleroderma
  Systemic sclerosis
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
• UniProt ID: RTCA_HUMAN
• EC Number: 6.5.1.4
• Pfam ID: PF01137 ; PF05189
• Sequence:
  MAGPRVEVDGSIMEGGGQILRVSTALSCLLGLPLRVQKIRAGRSTPGLRPQHLSGLEMIR
  DLCDGQLEGAEIGSTEITFTPEKIKGGIHTADTKTAGSVCLLMQVSMPCVLFAASPSELH
  LKGGTNAEMAPQIDYTVMVFKPIVEKFGFIFNCDIKTRGYYPKGGGEVIVRMSPVKQLNP
  INLTERGCVTKIYGRAFVAGVLPFKVAKDMAAAAVRCIRKEIRDLYVNIQPVQEPKDQAF
  GNGNGIIIIAETSTGCLFAGSSLGKRGVNADKVGIEAAEMLLANLRHGGTVDEYLQDQLI
  VFMALANGVSRIKTGPVTLHTQTAIHFAEQIAKAKFIVKKSEDEEDAAKDTYIIECQGIG
  MTNPNL
• Function: Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA. The mechanism of action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-phosphorus in the diester linkage to produce the cyclic end product. Likely functions in some aspects of cellular RNA processing. Function plays an important role in regulating axon regeneration by inhibiting central nervous system (CNS) axon regeneration following optic nerve injury.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary heart disease	DIS5OIP1	Definitive	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[2]
Central diabetes insipidus	DISJ4P9O	Strong	Biomarker	[3]
Epilepsy	DISBB28L	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[7]
Stroke	DISX6UHX	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[8]
Autoimmune disease	DISORMTM	moderate	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[9]
Connective tissue disorder	DISKXBS3	moderate	Biomarker	[8]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[9]
Scleroderma	DISVQ342	moderate	Biomarker	[8]
Systemic sclerosis	DISF44L6	moderate	Biomarker	[8]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[11]

9 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 RNA 3'-terminal phosphate cyclase (RTCA).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[19]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of RNA 3'-terminal phosphate cyclase (RTCA).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA 3'-terminal phosphate cyclase (RTCA).	[18]

References

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• [7] Adipocytes as lipid sensors of oleic acid transport through a functional Caco-2/HT29-MTX intestinal barrier.Adipocyte. 2019 Dec;8(1):83-97. doi: 10.1080/21623945.2019.1580842. Epub 2019 Mar 23.
• [8] Association of the autoimmune disease scleroderma with an immunologic response to cancer.Science. 2014 Jan 10;343(6167):152-7. doi: 10.1126/science.1246886. Epub 2013 Dec 5.
• [9] Combined Treatment with Valproic Acid and 5-Aza-2'-Deoxycytidine Synergistically Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration.Med Sci Monit. 2018 Feb 19;24:1034-1043. doi: 10.12659/msm.906020.
• [10] HSPC111 governs breast cancer growth by regulating ribosomal biogenesis.Mol Cancer Res. 2014 Apr;12(4):583-94. doi: 10.1158/1541-7786.MCR-13-0168. Epub 2014 Jan 14.
• [11] Next-generation sequencing analysis of multiplex families with atypical psychosis.Transl Psychiatry. 2018 Oct 15;8(1):221. doi: 10.1038/s41398-018-0272-x.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] 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.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [19] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [20] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [21] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.