Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB7J28X)

• DOT Name: Poly(A) RNA polymerase GLD2 (TENT2)
• Synonyms: hGLD-2; EC 2.7.7.19; PAP-associated domain-containing protein 4; Terminal nucleotidyltransferase 2; Terminal uridylyltransferase 2; TUTase 2
• Gene Name: TENT2
• Related Disease: Hepatocellular carcinoma
• UniProt ID: GLD2_HUMAN
• EC Number: 2.7.7.19
• Pfam ID: PF03828
• Sequence:
  MFPNSILGRPPFTPNHQQHNNFFTLSPTVYSHQQLIDAQFNFQNADLSRAVSLQQLTYGN
  VSPIQTSASPLFRGRKRLSDEKNLPLDGKRQRFHSPHQEPTVVNQIVPLSGERRYSMPPL
  FHTHYVPDIVRCVPPFREIAFLEPREITLPEAKDKLSQQILELFETCQQQISDLKKKELC
  RTQLQREIQLLFPQSRLFLVGSSLNGFGTRSSDGDLCLVVKEEPCFFQVNQKTEARHILT
  LVHKHFCTRLSGYIERPQLIRAKVPIVKFRDKVSCVEFDLNVNNIVGIRNTFLLRTYAYL
  ENRVRPLVLVIKKWASHHQINDASRGTLSSYSLVLMVLHYLQTLPEPILPSLQKIYPESF
  SPAIQLHLVHQAPCNVPPYLSKNESNLGDLLLGFLKYYATEFDWNSQMISVREAKAIPRP
  DGIEWRNKYICVEEPFDGTNTARAVHEKQKFDMIKDQFLKSWHRLKNKRDLNSILPVRAA
  VLKR
• Function: Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs. Does not play a role in replication-dependent histone mRNA degradation. Adds a single nucleotide to the 3' end of specific miRNAs, monoadenylation stabilizes and prolongs the activity of some but not all miRNAs.
• Tissue Specificity: Expressed in brain. Within brain, it is expressed in cerebellum, hippocampus and medulla.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Poly(A) RNA polymerase GLD2 (TENT2).	[8]

References

• [1] Hepatitis B virus X protein-induced upregulation of CAT-1 stimulates proliferation and inhibits apoptosis in hepatocellular carcinoma cells.Oncotarget. 2017 May 5;8(37):60962-60974. doi: 10.18632/oncotarget.17631. eCollection 2017 Sep 22.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] 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.