Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJSTU62)

• DOT Name: Nuclear receptor-binding protein 2 (NRBP2)
• Synonyms: Transformation-related gene 16 protein; TRG-16
• Gene Name: NRBP2
• Related Disease:
  Advanced cancer
  Cardiac failure
  Congestive heart failure
  Hepatocellular carcinoma
• UniProt ID: NRBP2_HUMAN
• Pfam ID: PF00069
• Sequence:
  MAAPEPAPRRAREREREREDESEDESDILEESPCGRWQKRREQVNQGNMPGLQSTFLAMD
  TEEGVEVVWNELHFGDRKAFAAHEEKIQTVFEQLVLVDHPNIVKLHKYWLDTSEACARVI
  FITEYVSSGSLKQFLKKTKKNHKAMNARAWKRWCTQILSALSFLHACSPPIIHGNLTSDT
  IFIQHNGLIKIGSVWHRIFSNALPDDLRSPIRAEREELRNLHFFPPEYGEVADGTAVDIF
  SFGMCALEMAVLEIQTNGDTRVTEEAIARARHSLSDPNMREFILCCLARDPARRPSAHSL
  LFHRVLFEVHSLKLLAAHCFIQHQYLMPENVVEEKTKAMDLHAVLAELPRPRRPPLQWRY
  SEVSFMELDKFLEDVRNGIYPLMNFAATRPLGLPRVLAPPPEEVQKAKTPTPEPFDSETR
  KVIQMQCNLERSEDKARWHLTLLLVLEDRLHRQLTYDLLPTDSAQDLASELVHYGFLHED
  DRMKLAAFLESTFLKYRGTQA
• Function: May regulate apoptosis of neural progenitor cells during their differentiation.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]

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 Nuclear receptor-binding protein 2 (NRBP2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear receptor-binding protein 2 (NRBP2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nuclear receptor-binding protein 2 (NRBP2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor-binding protein 2 (NRBP2).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Nuclear receptor-binding protein 2 (NRBP2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nuclear receptor-binding protein 2 (NRBP2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Nuclear receptor-binding protein 2 (NRBP2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nuclear receptor-binding protein 2 (NRBP2).	[9]

References

• [1] NRBP2 Overexpression Increases the Chemosensitivity of Hepatocellular Carcinoma Cells via Akt Signaling.Cancer Res. 2016 Dec 1;76(23):7059-7071. doi: 10.1158/0008-5472.CAN-16-0937. Epub 2016 Sep 7.
• [2] The altered expression of autophagy-related genes participates in heart failure: NRBP2 and CALCOCO2 are associated with left ventricular dysfunction parameters in human dilated cardiomyopathy.PLoS One. 2019 Apr 22;14(4):e0215818. doi: 10.1371/journal.pone.0215818. eCollection 2019.
• [3] 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.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [8] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.