Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT54GCY6)

DOT Name Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11)
Synonyms Pre-mRNA cleavage complex II protein Pcf11
Gene Name PCF11
Related Disease
Neoplasm ( )
Neuroblastoma ( )
UniProt ID
PCF11_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6WJH
Pfam ID
PF11526 ; PF04818 ; PF20827 ; PF20845 ; PF20844
Sequence
MSEQTPAEAGAAGAREDACRDYQSSLEDLTFNSKPHINMLTILAEENLPFAKEIVSLIEA
QTAKAPSSEKLPVMYLMDSIVKNVGREYLTAFTKNLVATFICVFEKVDENTRKSLFKLRS
TWDEIFPLKKLYALDVRVNSLDPAWPIKPLPPNVNTSSIHVNPKFLNKSPEEPSTPGTVV
SSPSISTPPIVPDIQKNLTQEQLIRQQLLAKQKQLLELQQKKLELELEQAKAQLAVSLSV
QQETSNLGPGSAPSKLHVSQIPPMAVKAPHQVPVQSEKSRPGPSLQIQDLKGTNRDPRLN
RISQHSHGKDQSHRKEFLMNTLNQSDTKTSKTIPSEKLNSSKQEKSKSGEKITKKELDQL
DSKSKSKSKSPSPLKNKLSHTKDLKNQESESMRLSDMNKRDPRLKKHLQDKTDGKDDDVK
EKRKTAEKKDKDEHMKSSEHRLAGSRNKIINGIVQKQDTITEESEKQGTKPGRSSTRKRS
RSRSPKSRSPIIHSPKRRDRRSPKRRQRSMSPTSTPKAGKIRQSGAKQSHMEEFTPPSRE
DRNAKRSTKQDIRDPRRMKKTEEERPQETTNQHSTKSGTEPKENVENWQSSKSAKRWKSG
WEENKSLQQVDEHSKPPHLRHRESWSSTKGILSPRAPKQQQHRLSVDANLQIPKELTLAS
KRELLQKTSERLASGEITQDDFLVVVHQIRQLFQYQEGVREEQRSPFNDRFPLKRPRYED
SDKPFVDSPASRFAGLDTNQRLTALAEDRPLFDGPSRPSVARDGPTKMIFEGPNKLSPRI
DGPPTPASLRFDGSPGQMGGGGPLRFEGPQGQLGGGCPLRFEGPPGPVGTPLRFEGPIGQ
AGGGGFRFEGSPGLRFEGSPGGLRFEGPGGQPVGGLRFEGHRGQPVGGLRFEGPHGQPVG
GLRFDNPRGQPVGGLRFEGGHGPSGAAIRFDGPHGQPGGGIRFEGPLLQQGVGMRFEGPH
GQSVAGLRFEGQHNQLGGNLRFEGPHGQPGVGIRFEGPLVQQGGGMRFEGPSVPGGGLRI
EGPLGQGGPRFEGCHALRFDGQPGQPSLLPRFDGLHGQPGPRFERTPGQPGPQRFDGPPG
QQVQPRFDGVPQRFDGPQHQQASRFDIPLGLQGTRFDNHPSQRLESVSFNQTGPYNDPPG
NAFNAPSQGLQFQRHEQIFDSPQGPNFNGPHGPGNQSFSNPLNRASGHYFDEKNLQSSQF
GNFGNIPAPMTVGNIQASQQVLSGVAQPVAFGQGQQFLPVHPQNPGFVQNPSGALPKAYP
DNHLSQVDVNELFSKLLKTGILKLSQTDSATTQVSEVTAQPPPEEEEDQNEDQDVPDLTN
FTVEELKQRYDSVINRLYTGIQCYSCGMRFTTSQTDVYADHLDWHYRQNRTEKDVSRKVT
HRRWYYSLTDWIEFEEIADLEERAKSQFFEKVHEEVVLKTQEAAKEKEFQSVPAGPAGAV
ESCEICQEQFEQYWDEEEEEWHLKNAIRVDGKIYHPSCYEDYQNTSSFDCTPSPSKTPVE
NPLNIMLNIVKNELQEPCDSPKVKEERIDTPPACTEESIATPSEIKTENDTVESV
Function Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II.
KEGG Pathway
mR. surveillance pathway (hsa03015 )
Reactome Pathway
mRNA 3'-end processing (R-HSA-72187 )
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 )
RNA polymerase II transcribes snRNA genes (R-HSA-6807505 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Limited Biomarker [1]
Neuroblastoma DISVZBI4 Limited Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [6]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [7]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [12]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [7]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [7]
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⏷ Show the Full List of 6 Drug(s)
10 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 Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [5]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [8]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [10]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [14]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Pre-mRNA cleavage complex 2 protein Pcf11 (PCF11). [15]
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⏷ Show the Full List of 10 Drug(s)

References

1 Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma.Nat Commun. 2018 Dec 14;9(1):5331. doi: 10.1038/s41467-018-07580-5.
2 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.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
6 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.
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 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
11 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
12 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
13 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.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
15 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.