Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZW1RQS)

• DOT Name: NEDD4-binding protein 3 (N4BP3)
• Synonyms: N4BP3
• Gene Name: N4BP3
• UniProt ID: N4BP3_HUMAN
• Pfam ID: PF06818
• Sequence:
  MATAPGPAGIAMGSVGSLLERQDFSPEELRAALAGSRGSRQPDGLLRKGLGQREFLSYLH
  LPKKDSKSTKNTKRAPRNEPADYATLYYREHSRAGDFSKTSLPERGRFDKCRIRPSVFKP
  TAGNGKGFLSMQSLASHKGQKLWRSNGSLHTLACHPPLSPGPRASQARAQLLHALSLDEG
  GPEPEPSLSDSSSGGSFGRSPGTGPSPFSSSLGHLNHLGGSLDRASQGPKEAGPPAVLSC
  LPEPPPPYEFSCSSAEEMGAVLPETCEELKRGLGDEDGSNPFTQVLEERQRLWLAELKRL
  YVERLHEVTQKAERSERNLQLQLFMAQQEQRRLRKELRAQQGLAPEPRAPGTLPEADPSA
  RPEEEARWEVCQKTAEISLLKQQLREAQAELAQKLAEIFSLKTQLRGSRAQAQAQDAELV
  RLREAVRSLQEQAPREEAPGSCETDDCKSRGLLGEAGGSEARDSAEQLRAELLQERLRGQ
  EQALRFEQERRTWQEEKERVLRYQREIQGGYMDMYRRNQALEQELRALREPPTPWSPRLE
  SSKI
• Function: Plays a positive role in the antiviral innate immune signaling pathway. Mechanistically, interacts with MAVS and functions as a positive regulator to promote 'Lys-63'-linked polyubiquitination of MAVS and thus strengthens the interaction between MAVS and TRAF2. Also plays a role in axon and dendrite arborization during cranial nerve development. May also be important for neural crest migration and early development of other anterior structures including eye, brain and cranial cartilage.

Molecular Interaction Atlas (MIA) of This DOT

13 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 NEDD4-binding protein 3 (N4BP3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NEDD4-binding protein 3 (N4BP3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of NEDD4-binding protein 3 (N4BP3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NEDD4-binding protein 3 (N4BP3).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of NEDD4-binding protein 3 (N4BP3).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of NEDD4-binding protein 3 (N4BP3).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of NEDD4-binding protein 3 (N4BP3).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of NEDD4-binding protein 3 (N4BP3).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of NEDD4-binding protein 3 (N4BP3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of NEDD4-binding protein 3 (N4BP3).	[1]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of NEDD4-binding protein 3 (N4BP3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of NEDD4-binding protein 3 (N4BP3).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of NEDD4-binding protein 3 (N4BP3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of NEDD4-binding protein 3 (N4BP3).	[10]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [10] 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.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.