Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOWVQ4O)

• DOT Name: Terminal nucleotidyltransferase 5C (TENT5C)
• Synonyms: EC 2.7.7.19; Non-canonical poly(A) polymerase FAM46C
• Gene Name: TENT5C
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Plasma cell myeloma
  Neoplasm
  Squamous cell carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: TET5C_HUMAN
• PDB ID: 6W36; 6W38; 6W3I; 6W3J; 8EQB
• EC Number: 2.7.7.19
• Pfam ID: PF07984
• Sequence:
  MAEESSCTRDCMSFSVLNWDQVSRLHEVLTEVVPIHGRGNFPTLEITLKDIVQTVRSRLE
  EAGIKVHDVRLNGSAAGHVLVKDNGLGCKDLDLIFHVALPTEAEFQLVRDVVLCSLLNFL
  PEGVNKLKISPVTLKEAYVQKLVKVCTDTDRWSLISLSNKNGKNVELKFVDSIRRQFEFS
  VDSFQIILDSLLFFYDCSNNPISEHFHPTVIGESMYGDFEEAFDHLQNRLIATKNPEEIR
  GGGLLKYSNLLVRDFRPTDQEEIKTLERYMCSRFFIDFPDILEQQRKLETYLQNHFAEEE
  RSKYDYLMILRRVVNESTVCLMGHERRQTLNLISLLALRVLAEQNIIPSATNVTCYYQPA
  PYVSDGNFSNYYVAHPPVTYSQPYPTWLPCN
• Function: Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group and enhances mRNA stability and gene expression. Can also elongate RNA oligos ending with uridine molecule, provided that the sequence is adenosine-rich. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein ; (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[4]

26 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 Terminal nucleotidyltransferase 5C (TENT5C).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[16]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[18]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[19]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[21]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[23]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[26]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Terminal nucleotidyltransferase 5C (TENT5C).	[27]

References

• [1] Antimetastatic effects of norcantharidin on hepatocellular carcinoma cells by up-regulating FAM46C expression.Am J Transl Res. 2017 Jan 15;9(1):155-166. eCollection 2017.
• [2] FAM46C is critical for the anti-proliferation and pro-apoptotic effects of norcantharidin in hepatocellular carcinoma cells.Sci Rep. 2017 Mar 24;7(1):396. doi: 10.1038/s41598-017-00313-6.
• [3] The potential functions of FAM46C in oral squamous cell carcinoma.Onco Targets Ther. 2018 Dec 10;11:8915-8923. doi: 10.2147/OTT.S185244. eCollection 2018.
• [4] FAM46C suppresses gastric cancer by inhibition of Wnt/beta-catenin.Front Biosci (Landmark Ed). 2020 Jan 1;25(3):549-563. doi: 10.2741/4820.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [12] 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.
• [13] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [14] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] 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.
• [20] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [23] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [24] 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.
• [25] 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.
• [26] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [27] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.