Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1Y7B5U)

• DOT Name: Cleavage stimulation factor subunit 3 (CSTF3)
• Synonyms: CF-1 77 kDa subunit; Cleavage stimulation factor 77 kDa subunit; CSTF 77 kDa subunit; CstF-77
• Gene Name: CSTF3
• Related Disease:
  Major depressive disorder
  Mood disorder
  Neoplasm
  Rheumatoid arthritis
• UniProt ID: CSTF3_HUMAN
• PDB ID: 6B3X; 6URO; 7ZY4
• Pfam ID: PF05843
• Sequence:
  MSGDGATEQAAEYVPEKVKKAEKKLEENPYDLDAWSILIREAQNQPIDKARKTYERLVAQ
  FPSSGRFWKLYIEAEIKAKNYDKVEKLFQRCLMKVLHIDLWKCYLSYVRETKGKLPSYKE
  KMAQAYDFALDKIGMEIMSYQIWVDYINFLKGVEAVGSYAENQRITAVRRVYQRGCVNPM
  INIEQLWRDYNKYEEGINIHLAKKMIEDRSRDYMNARRVAKEYETVMKGLDRNAPSVPPQ
  NTPQEAQQVDMWKKYIQWEKSNPLRTEDQTLITKRVMFAYEQCLLVLGHHPDIWYEAAQY
  LEQSSKLLAEKGDMNNAKLFSDEAANIYERAISTLLKKNMLLYFAYADYEESRMKYEKVH
  SIYNRLLAIEDIDPTLVYIQYMKFARRAEGIKSGRMIFKKAREDTRTRHHVYVTAALMEY
  YCSKDKSVAFKIFELGLKKYGDIPEYVLAYIDYLSHLNEDNNTRVLFERVLTSGSLPPEK
  SGEIWARFLAFESNIGDLASILKVEKRRFTAFKEEYEGKETALLVDRYKFMDLYPCSASE
  LKALGYKDVSRAKLAAIIPDPVVAPSIVPVLKDEVDRKPEYPKPDTQQMIPFQPRHLAPP
  GLHPVPGGVFPVPPAAVVLMKLLPPPICFQGPFVQVDELMEIFRRCKIPNTVEEAVRIIT
  GGAPELAVEGNGPVESNAVLTKAVKRPNEDSDEDEEKGAVVPPVHDIYRARQQKRIR
• Function: One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Processing of Intronless Pre-mRNAs (R-HSA-77595)
  mRNA 3'-end processing (R-HSA-72187)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]

16 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 Cleavage stimulation factor subunit 3 (CSTF3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cleavage stimulation factor subunit 3 (CSTF3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cleavage stimulation factor subunit 3 (CSTF3).	[16]

References

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• [2] Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation.Cancer Res. 2016 Dec 15;76(24):7231-7241. doi: 10.1158/0008-5472.CAN-16-0844. Epub 2016 Oct 10.
• [3] Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [13] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.