Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIJ1KQI)

• DOT Name: U3 small nucleolar RNA-associated protein NOL7 (NOL7)
• Synonyms: U3 snoRNA-associated protein NOL7; Nucleolar protein 7; Nucleolar protein of 27 kDa
• Gene Name: NOL7
• Related Disease:
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Neoplasm
  Precancerous condition
  Retinoblastoma
• UniProt ID: UTP16_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF08157
• Sequence:
  MVQLRPRASRAPASAEAMVDEGQLASEEEEAEHGLLLGQPSSGAAAEPLEEDEEGDDEFD
  DEAPEELTFASAQAEAREEERRVRETVRRDKTLLKEKRKRREELFIEQKKRKLLPDTILE
  KLTTASQTNIKKSPGKVKEVNLQKKNEDCEKGNDSKKVKVQKVQSVSQNKSYLAVRLKDQ
  DLRDSRQQAAQAFIHNSLYGPGTNRTTVNKFLSLANKRLPVKRAAVQFLNNAWGIQKKQN
  AKRFKRRWMVRKMKTKK
• Function: Functions as part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit that coordinates the first two steps of ribosome biogenesis in transcription of the primary transcript pre-RNA and pre-18S processing. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. This subunit is required for processing of the 5'-external transcribed spacer sequence (5'ETS) of the primary transcript pre-rRNA to yield the 18S rRNA. Also plays a role in maintaining early pre-rRNA levels, either by assisting in its transcription or stability.
• Tissue Specificity: Expressed in numerous tissues. Particularly prevalent in the adrenal gland, thyroid gland, heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Precancerous condition	DISV06FL	Strong	Altered Expression	[1]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[1]

10 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 U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[9]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the methylation of U3 small nucleolar RNA-associated protein NOL7 (NOL7).	[14]

References

• [1] The RB tumor suppressor positively regulates transcription of the anti-angiogenic protein NOL7.Neoplasia. 2012 Dec;14(12):1213-22. doi: 10.1593/neo.121422.
• [2] Characterization of NOL7 gene point mutations, promoter methylation, and protein expression in cervical cancer.Int J Gynecol Pathol. 2012 Jan;31(1):15-24. doi: 10.1097/PGP.0b013e318220ba16.
• [3] The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression.Oncogene. 2013 Sep 12;32(37):4377-86. doi: 10.1038/onc.2012.464. Epub 2012 Oct 22.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [14] Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.