Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5MJ1VF)

• DOT Name: Nucleolar protein 12 (NOL12)
• Gene Name: NOL12
• UniProt ID: NOL12_HUMAN
• Pfam ID: PF09805
• Sequence:
  MGRNKKKKRDGDDRRPRLVLSFDEEKRREYLTGFHKRKVERKKAAIEEIKQRLKEEQRKL
  REERHQEYLKMLAEREEALEEADELDRLVTAKTESVQYDHPNHTVTVTTISDLDLSGARL
  LGLTPPEGGAGDRSEEEASSTEKPTKALPRKSRDPLLSQRISSLTASLHAHSRKKVKRKH
  PRRAQDSKKPPRAPRTSKAQRRRLTGKARHSGE
• Function: Multifunctional RNA binding protein that plays a role in RNA metabolism and DNA maintenance. Participates in the resolution of DNA stress and the maintenance of genome integrity by localizing to sites of DNA insults. Plays also a role in proper nucleolar organization by limiting nucleolar size and regulating nucleolar number. Mechanistically, regulates the nucleolar levels of fibrillarin and nucleolin, two key players in pre-rRNA processing and ribosome assembly.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Nucleolar protein 12 (NOL12).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleolar protein 12 (NOL12).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Nucleolar protein 12 (NOL12).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nucleolar protein 12 (NOL12).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleolar protein 12 (NOL12).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleolar protein 12 (NOL12).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nucleolar protein 12 (NOL12).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Nucleolar protein 12 (NOL12).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Nucleolar protein 12 (NOL12).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nucleolar protein 12 (NOL12).	[4]

References

• [1] 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.
• [2] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.