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

DOT Name Exosome complex component RRP42 (EXOSC7)
Synonyms Exosome component 7; Ribosomal RNA-processing protein 42; p8
Gene Name EXOSC7
Related Disease
Fragile X-associated tremor/ataxia syndrome ( )
UniProt ID
EXOS7_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2NN6; 6D6Q; 6D6R; 6H25
Pfam ID
PF01138 ; PF03725
Sequence
MASVTLSEAEKVYIVHGVQEDLRVDGRGCEDYRCVEVETDVVSNTSGSARVKLGHTDILV
GVKAEMGTPKLEKPNEGYLEFFVDCSASATPEFEGRGGDDLGTEIANTLYRIFNNKSSVD
LKTLCISPREHCWVLYVDVLLLECGGNLFDAISIAVKAALFNTRIPRVRVLEDEEGSKDI
ELSDDPYDCIRLSVENVPCIVTLCKIGYRHVVDATLQEEACSLASLLVSVTSKGVVTCMR
KVGKGSLDPESIFEMMETGKRVGKVLHASLQSVVHKEESLGPKRQKVGFLG
Function
Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes.
KEGG Pathway
R. degradation (hsa03018 )
Reactome Pathway
mRNA decay by 3' to 5' exoribonuclease (R-HSA-429958 )
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA (R-HSA-450385 )
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA (R-HSA-450513 )
KSRP (KHSRP) binds and destabilizes mRNA (R-HSA-450604 )
Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )
ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Fragile X-associated tremor/ataxia syndrome DISKB25R Strong 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 Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Exosome complex component RRP42 (EXOSC7). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Exosome complex component RRP42 (EXOSC7). [3]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Exosome complex component RRP42 (EXOSC7). [4]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Exosome complex component RRP42 (EXOSC7). [6]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN affects the expression of Exosome complex component RRP42 (EXOSC7). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Exosome complex component RRP42 (EXOSC7). [8]
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⏷ Show the Full List of 6 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Exosome complex component RRP42 (EXOSC7). [5]
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References

1 Blood expression profiles of fragile X premutation carriers identify candidate genes involved in neurodegenerative and infertility phenotypes.Neurobiol Dis. 2014 May;65:43-54. doi: 10.1016/j.nbd.2013.12.020. Epub 2014 Jan 10.
2 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 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.
5 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.
6 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
7 DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer thapsigargin based on comparative gene expression profiling in Jurkat T cells. Toxicol Lett. 2014 Jan 30;224(3):395-406. doi: 10.1016/j.toxlet.2013.11.005. Epub 2013 Nov 15.
8 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.