Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAMQ4EI)

• DOT Name: Nicolin-1 (NICN1)
• Synonyms: NPCEDRG; Tubulin polyglutamylase complex subunit 5; PGs5
• Gene Name: NICN1
• Related Disease:
  Nasopharyngeal carcinoma
  Crohn disease
• UniProt ID: NICN1_HUMAN
• Sequence:
  MSRVLVPCHVKGSVALQVGDVRTSQGRPGVLVIDVTFPSVAPFELQEITFKNYYTAFLSI
  RVRQYTSAHTPAKWVTCLRDYCLMPDPHSEEGAQEYVSLFKHQMLCDMARISELRLILRQ
  PSPLWLSFTVEELQIYQQGPKSPSVTFPKWLSHPVPCEQPALLREGLPDPSRVSSEVQQM
  WALTEMIRASHTSARIGRFDVDGCYDLNLLSYT
• Tissue Specificity: High expression level is found in brain, testis, liver and kidney. Weak expression in spleen, leukocytes, small intestine and colon.
• Reactome Pathway: Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[1]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[2]

8 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 Nicolin-1 (NICN1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nicolin-1 (NICN1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nicolin-1 (NICN1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nicolin-1 (NICN1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nicolin-1 (NICN1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nicolin-1 (NICN1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nicolin-1 (NICN1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nicolin-1 (NICN1).	[10]

References

• [1] Cloning and characterization of the NPCEDRG gene promoter.Mol Cell Biochem. 2011 Jan;346(1-2):1-10. doi: 10.1007/s11010-010-0584-5. Epub 2010 Sep 7.
• [2] Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci.Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14747-52. doi: 10.1073/pnas.0706645104. Epub 2007 Sep 5.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.