Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW9L6S4)

• DOT Name: RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72)
• Synonyms: CTD phosphatase SSU72; EC 3.1.3.16
• Gene Name: SSU72
• UniProt ID: SSU72_HUMAN
• PDB ID: 3O2Q; 3O2S; 4H3H; 4H3K
• EC Number: 3.1.3.16
• Pfam ID: PF04722
• Sequence:
  MPSSPLRVAVVCSSNQNRSMEAHNILSKRGFSVRSFGTGTHVKLPGPAPDKPNVYDFKTT
  YDQMYNDLLRKDKELYTQNGILHMLDRNKRIKPRPERFQNCKDLFDLILTCEERVYDQVV
  EDLNSREQETCQPVHVVNVDIQDNHEEATLGAFLICELCQCIQHTEDMENEIDELLQEFE
  EKSGRTFLHTVCFY
• Function: Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. Plays a role in pre-mRNA polyadenylation via its interaction with SYMPK.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway: RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

3 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 RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[6]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RNA polymerase II subunit A C-terminal domain phosphatase SSU72 (SSU72).	[9]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [9] 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.
• [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.