Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4WE5J7)

• DOT Name: Cleavage and polyadenylation specificity factor subunit 7 (CPSF7)
• Synonyms: Cleavage and polyadenylation specificity factor 59 kDa subunit; CPSF 59 kDa subunit; Cleavage factor Im complex 59 kDa subunit; CFIm59; Pre-mRNA cleavage factor Im 59 kDa subunit
• Gene Name: CPSF7
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Liver cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: CPSF7_HUMAN
• PDB ID: 3N9U
• Pfam ID: PF00076
• Sequence:
  MSEGVDLIDIYADEEFNQDPEFNNTDQIDLYDDVLTATSQPSDDRSSSTEPPPPVRQEPS
  PKPNNKTPAILYTYSGLRNRRAAVYVGSFSWWTTDQQLIQVIRSIGVYDVVELKFAENRA
  NGQSKGYAEVVVASENSVHKLLELLPGKVLNGEKVDVRPATRQNLSQFEAQARKRECVRV
  PRGGIPPRAHSRDSSDSADGRATPSENLVPSSARVDKPPSVLPYFNRPPSALPLMGLPPP
  PIPPPPPLSSSFGVPPPPPGIHYQHLMPPPPRLPPHLAVPPPGAIPPALHLNPAFFPPPN
  ATVGPPPDTYMKASAPYNHHGSRDSGPPPSTVSEAEFEDIMKRNRAISSSAISKAVSGAS
  AGDYSDAIETLLTAIAVIKQSRVANDERCRVLISSLKDCLHGIEAKSYSVGASGSSSRKR
  HRSRERSPSRSRESSRRHRDLLHNEDRHDDYFQERNREHERHRDRERDRHH
• Function: Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. CPSF7 activates directly the mRNA 3'-processing machinery. Binds to pA signals in RNA substrates.
• KEGG Pathway:
  mR. surveillance pathway (hsa03015)
  Viral life cycle - HIV-1 (hsa03250)
• 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)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  mRNA 3'-end processing (R-HSA-72187)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]

6 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 Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[9]

2 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 and polyadenylation specificity factor subunit 7 (CPSF7).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Cleavage and polyadenylation specificity factor subunit 7 (CPSF7).	[7]

References

• [1] CPSF7 regulates liver cancer growth and metastasis by facilitating WWP2-FL and targeting the WWP2/PTEN/AKT signaling pathway.Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118624. doi: 10.1016/j.bbamcr.2019.118624. Epub 2019 Dec 12.
• [2] MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion.J Pathol. 2013 Nov;231(3):388-99. doi: 10.1002/path.4248.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] 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.
• [5] 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.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] 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.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [9] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.