Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAZ55UQ)

• DOT Name: Neuroblastoma breakpoint family member 1 (NBPF1)
• Gene Name: NBPF1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast fibrocystic disease
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Herpes simplex infection
  Neoplasm
  Neuroblastoma
  Cutaneous squamous cell carcinoma
• UniProt ID: NBPF1_HUMAN
• Pfam ID: PF06758
• Sequence:
  MVVSAGPWSSEKAETNILEINEKLRPQLAENKQQFRNLKEKCFVTQLAGFLANRQKKYKY
  EECKDLIKFMLRNERQFKEEKLAEQLKQAEELRQYKVLVHSQERELTQLREKLREGRDAS
  RSLNQHLQALLTPDKPDKSQGQDLQEQLAEGCRLAQQLFQKLSPENDEDEDEDVQVEEAE
  KVLESSAPREVQKAEESKVPEDSLEECAITCSNSHSPCDSNQPHKNINITFEEDKVNSTL
  VVDRESSHDECQDAVNILPVPGPTSSATNVSMVVSAGPLSSEKAEMNILEINEKLHPQLA
  EKKQQFRNLKEKCFVTQLACFLANQQNKYKYEECKDLIKSMLRNERQFKEEKLAEQLKQA
  EELRQYKVLVHSQERELTQLREKLREGRDASRSLNQHLQALLTPDKPDKSQGQDLQEQLA
  EGCRLAQQLFQKLSPENDEDEDEDVQVEEAEKVLESSAPREVQKAEESKVPEDSLEECAI
  TCSNSHGPCDSNQPHKNINITFEEDKVNSALVVDRESSHDECQDAVNILPVPGPTSSATN
  VSMVVSAGPLSSEKAEMNILEINEKLHPQLAEKKQQFRNLKEKCFVTQLACFLANQQNKY
  KNEECKDLIKSMLRNERQFKEEKLAEQLKQAEELRQYKVLVHSQERELTQLREKLREGRD
  ASCSLNQHLQALLTPDEPDKSQGQDLQEQLAEGCRLAQHLVQKLSPENDNDDDEDVQVEV
  AEKVQKSSAPREMPKAEEKEVPEDSLEECAITCSNSHGPYDSNQPHRKTKITFEEDKVDS
  TLIGSSSHVEWEDAVHIIPENESDDEEEEEKGPVSPRNLQESEEEEVPQESWDEGYSTLS
  IPPEMLASYKSYSGTFHSLEEQQVCMAVDIGGHRWDQVKKEDQEATGPRLSRELLDEKGP
  EVLQDSLDRCYSTPSGYLELTDSCQPYRSAFYILEQQRVGWALDMDEIEKYQEVEEDQDP
  SCPRLSRELLDEKEPEVLQDSLDRCYSTPSGYLELPDLGQPYRSAVYSLEEQYLGLALDV
  DRIKKDQEEEEDQGPPCPRLSRELLEAVEPEVLQDSLDRCYSTPSSCLEQPDSCLPYGSS
  FYALEEKHVGFSLDVGEIEKKGKGKKRRGRRSTKKRRRRGRKEGEEDQNPPCPRLSGMLM
  EVEEPEVLQDSLDRCYSTPSMYFELPDSFQHYRSVFYSFEEQHISFALDVDNRFLTLMGT
  SLHLVFQMGVIFPQ
• Tissue Specificity: Widely expressed. The only tissue which shows a weak expression is kidney.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[1]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[1]
Breast fibrocystic disease	DISUM7ID	Strong	Genetic Variation	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[5]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[4]

10 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 Neuroblastoma breakpoint family member 1 (NBPF1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Neuroblastoma breakpoint family member 1 (NBPF1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Neuroblastoma breakpoint family member 1 (NBPF1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neuroblastoma breakpoint family member 1 (NBPF1).	[14]

References

• [1] Methylation of NBPF1 as a novel marker for the detection of plasma cell-free DNA of breast cancer patients.Clin Chim Acta. 2018 Sep;484:81-86. doi: 10.1016/j.cca.2018.05.030. Epub 2018 May 15.
• [2] Tumor-Suppressor Gene NBPF1 Inhibits Invasion and PI3K/mTOR Signaling in Cervical Cancer Cells.Oncol Res. 2016 Jan 21;23(1-2):13-20. doi: 10.3727/096504015X14410238486766.
• [3] Proteins containing only half of the coding information of early region 1b of adenovirus are functional in human cells transformed with the herpes simplex virus type 1 thymidine kinase gene and adenovirus type 2 DNA.J Virol. 1982 Feb;41(2):423-34. doi: 10.1128/JVI.41.2.423-434.1982.
• [4] Effects of neuroblastoma breakpoint family member 1 (NBPF1) gene on growth and Akt-p53-Cyclin D pathway in cutaneous squamous carcinoma cells.Neoplasma. 2019 Jul 23;66(4):584-592. doi: 10.4149/neo_2018_181123N888. Epub 2019 Apr 24.
• [5] Integration of gene expression and methylation to unravel biological networks in glioblastoma patients.Genet Epidemiol. 2017 Feb;41(2):136-144. doi: 10.1002/gepi.22028. Epub 2016 Dec 26.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.