Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH0J5CV)

• DOT Name: Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1)
• Synonyms: EC 3.1.3.16; Nuclear LIM interactor-interacting factor 3; NLI-IF; NLI-interacting factor 3; Small C-terminal domain phosphatase 1; SCP1; Small CTD phosphatase 1
• Gene Name: CTDSP1
• UniProt ID: CTDS1_HUMAN
• PDB ID: 1T9Z; 1TA0; 2GHQ; 2GHT; 3L0B; 3L0C; 3L0Y; 3PGL; 4YGY; 4YH1; 6DU3
• EC Number: 3.1.3.16
• Pfam ID: PF03031
• Sequence:
  MDSSAVITQISKEEARGPLRGKGDQKSAASQKPRSRGILHSLFCCVCRDDGEALPAHSGA
  PLLVEENGAIPKQTPVQYLLPEAKAQDSDKICVVIDLDETLVHSSFKPVNNADFIIPVEI
  DGVVHQVYVLKRPHVDEFLQRMGELFECVLFTASLAKYADPVADLLDKWGAFRARLFRES
  CVFHRGNYVKDLSRLGRDLRRVLILDNSPASYVFHPDNAVPVASWFDNMSDTELHDLLPF
  FEQLSRVDDVYSVLRQPRPGS
• Function: Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.
• Tissue Specificity: Expression is restricted to non-neuronal tissues. Highest expression in skeletal muscle, spleen, lung and placenta.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1) decreases the response to substance of Cisplatin.	[12]

2 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 Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[9]

9 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 Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1).	[11]

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] 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] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [6] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [7] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [8] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.