Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRM16MN)

• DOT Name: Neuroblastoma breakpoint family member 3 (NBPF3)
• Synonyms: Protein AE2; Protein SHIIIa4
• Gene Name: NBPF3
• Related Disease:
  B-cell neoplasm
  Hepatocellular carcinoma
  Primary biliary cholangitis
• UniProt ID: NBPF3_HUMAN
• Pfam ID: PF06758
• Sequence:
  MPLTPTVQGFQWTLRGPDVETSPFGAPRAASHGVGRHQELRDPTVPGPTSSATNVSMVVS
  AGPWSGEKAEMNILEINKKSRPQLAENKQQFRNLKQKCLVTQVAYFLANRQNNYDYEDCK
  DLIKSMLRDERLLTEEKLAEELGQAEELRQYKVLVHSQERELTQLREKLQEGRDASRSLN
  QHLQALLTPDEPDNSQGRDLREQLAEGCRLAQHLVQKLSPENDDDEDEDVKVEEAEKVQE
  LYAPREVQKAEEKEVPEDSLEECAITCSNSHHPCESNQPYGNTRITFEEDQVDSTLIDSS
  SHDEWLDAVCIIPENESDHEQEEEKGPVSPRNLQESEEEEAPQESWDEGDWTLSIPPDMS
  ASYQSDRSTFHSVEEQQVGLALDIGRHWCDQVKKEDQEATSPRLSRELLDEKEPEVLQDS
  LDRFYSTPFEYLELPDLCQPYRSDFYSLQEQHLGLALDLDRMKKDQEEEEDQGPPCPRLS
  RELPEVVEPEDLQDSLDRWYSTPFSYPELPDSCQPYGSCFYSLEEEHVGFSLDVDEIEKY
  QEGEEDQKPPCPRLNEVLMEAEEPEVLQDSLDRCYSTTSTYFQLHASFQQYRSAFYSFEE
  QDVSLALDVDNRFFTLTVIRHHLAFQMGVIFPH
• Tissue Specificity: Expressed in testis and fetal heart, as well as in non small cell lung carcinoma and neuroblastoma cell line.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Primary biliary cholangitis	DIS43E0O	Disputed	Altered Expression	[3]

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 Neuroblastoma breakpoint family member 3 (NBPF3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Neuroblastoma breakpoint family member 3 (NBPF3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[10]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Neuroblastoma breakpoint family member 3 (NBPF3).	[11]

References

• [1] Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms.Haematologica. 2018 Jun;103(6):1065-1072. doi: 10.3324/haematol.2017.175687. Epub 2017 Nov 30.
• [2] Reduction of anion exchanger 2 expression induces apoptosis of human hepatocellular carcinoma cells.Mol Cell Biochem. 2009 Jul;327(1-2):135-44. doi: 10.1007/s11010-009-0051-3. Epub 2009 Feb 18.
• [3] Role of the anion exchanger 2 in the pathogenesis and treatment of primary biliary cirrhosis.Dig Dis. 2011;29(1):103-12. doi: 10.1159/000324144. Epub 2011 Jun 17.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] 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.
• [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] 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.
• [11] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.