Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2P28B)

• DOT Name: Terminal nucleotidyltransferase 5B (TENT5B)
• Synonyms: EC 2.7.7.19; Non-canonical poly(A) polymerase FAM46B
• Gene Name: TENT5B
• Related Disease:
  Advanced cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: TET5B_HUMAN
• EC Number: 2.7.7.19
• Pfam ID: PF07984
• Sequence:
  MMPSESGAERRDRAAAQVGTAAATAVATAAPAGGGPDPEALSAFPGRHLSGLSWPQVKRL
  DALLSEPIPIHGRGNFPTLSVQPRQIVQVVRSTLEEQGLHVHSVRLHGSAASHVLHPESG
  LGYKDLDLVFRVDLRSEASFQLTKAVVLACLLDFLPAGVSRAKITPLTLKEAYVQKLVKV
  CTDSDRWSLISLSNKSGKNVELKFVDSVRRQFEFSIDSFQIILDSLLLFGQCSSTPMSEA
  FHPTVTGESLYGDFTEALEHLRHRVIATRSPEEIRGGGLLKYCHLLVRGFRPRPSTDVRA
  LQRYMCSRFFIDFPDLVEQRRTLERYLEAHFGGADAARRYACLVTLHRVVNESTVCLMNH
  ERRQTLDLIAALALQALAEQGPAATAALAWRPPGTDGVVPATVNYYVTPVQPLLAHAYPT
  WLPCN
• Function: Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group in an ATP hydrolysis-dependent manner. May be involved in maintaining the translation efficiency of at least some genes through preventing degradation of their mRNAs. Prefers RNA molecules that are adenosine-rich close to 3'-end. In addition, may inhibit cell proliferation and cell cycle progression through ubiquitination of beta-catenin/CTNNB1.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]

18 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 5B (TENT5B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[14]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Terminal nucleotidyltransferase 5B (TENT5B).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Terminal nucleotidyltransferase 5B (TENT5B).	[10]

References

• [1] FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of -catenin.Exp Mol Med. 2018 Dec 10;50(12):1-12. doi: 10.1038/s12276-018-0184-0.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] 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.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] 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.
• [10] 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.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
• [19] 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.