Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNP4LEO)

• DOT Name: Nuclear receptor 2C2-associated protein (NR2C2AP)
• Synonyms: TR4 orphan receptor-associated 16 kDa protein
• Gene Name: NR2C2AP
• Related Disease:
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: NR2CA_HUMAN
• Sequence:
  MTHSLVCPETVSRVSSVLNRNTRQFGKKHLFDQDEETCWNSDQGPSQWVTLEFPQLIRVS
  QLQIQFQGGFSSRRGCLEGSQGTQALHKIVDFYPEDNNSLQTFPIPAAEVDRLKVTFEDA
  TDFFGRVVIYHLRVLGEKV
• Function: May act as a repressor of NR2C2-mediated transactivation by suppressing the binding between NR2C2/TR4 and the TR4-response element in target genes.
• Tissue Specificity: Expressed in all tissues examined, with highest expression in heart, skeletal muscle and pancreas.
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

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	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Nuclear receptor 2C2-associated protein (NR2C2AP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nuclear receptor 2C2-associated protein (NR2C2AP).	[9]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear receptor 2C2-associated protein (NR2C2AP).	[12]

References

• [1] Testicular orphan nuclear receptor 4-associated protein 16 promotes non-small cell lung carcinoma by activating estrogen receptor and blocking testicular orphan nuclear receptor2.Oncol Rep. 2013 Jan;29(1):297-305. doi: 10.3892/or.2012.2107. Epub 2012 Oct 26.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.