Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT2BOJG)

• DOT Name: Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2)
• Synonyms: EC 3.1.3.16; Nuclear LIM interactor-interacting factor 2; NLI-interacting factor 2; Protein OS-4; Small C-terminal domain phosphatase 2; Small CTD phosphatase 2; SCP2
• Gene Name: CTDSP2
• Related Disease:
  Alzheimer disease
  Hyperglycemia
  Periodontal disease
• UniProt ID: CTDS2_HUMAN
• PDB ID: 2Q5E
• EC Number: 3.1.3.16
• Pfam ID: PF03031
• Sequence:
  MEHGSIITQARREDALVLTKQGLVSKSSPKKPRGRNIFKALFCCFRAQHVGQSSSSTELA
  AYKEEANTIAKSDLLQCLQYQFYQIPGTCLLPEVTEEDQGRICVVIDLDETLVHSSFKPI
  NNADFIVPIEIEGTTHQVYVLKRPYVDEFLRRMGELFECVLFTASLAKYADPVTDLLDRC
  GVFRARLFRESCVFHQGCYVKDLSRLGRDLRKTLILDNSPASYIFHPENAVPVQSWFDDM
  ADTELLNLIPIFEELSGAEDVYTSLGQLRAP
• 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. May contribute to the development of sarcomas.
• Tissue Specificity: Expression is restricted to non-neuronal tissues. Highest expression in pancreas and lowest in liver.
• Reactome Pathway: XBP1(S) activates chaperone genes (R-HSA-381038)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[2]
Periodontal disease	DISJQHVN	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (CTDSP2).	[14]

References

• [1] The sterol carrier protein SCP-x/pro-SCP-2 gene has transcriptional activity and regulates the Alzheimer disease gamma-secretase.J Biol Chem. 2007 Jul 6;282(27):19742-52. doi: 10.1074/jbc.M611426200. Epub 2007 May 7.
• [2] Physicochemical properties of polysaccharides separated from Camellia oleifera Abel seed cake and its hypoglycemic activity on streptozotocin-induced diabetic mice.Int J Biol Macromol. 2019 Mar 15;125:1075-1083. doi: 10.1016/j.ijbiomac.2018.12.059. Epub 2018 Dec 5.
• [3] Effects of smoking and genotype on the PSR index of periodontal disease in adults aged 18-49.Int J Environ Res Public Health. 2012 Aug;9(8):2839-50. doi: 10.3390/ijerph9082839. Epub 2012 Aug 10.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.