Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1JMTBD)

• DOT Name: Protein BANP (BANP)
• Synonyms: BEN domain-containing protein 1; Btg3-associated nuclear protein; Scaffold/matrix-associated region-1-binding protein
• Gene Name: BANP
• Related Disease:
  Advanced cancer
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colitis
  Colorectal carcinoma
  Keratoconus
  Melanoma
  Metastatic malignant neoplasm
  Neoplasm
  Rheumatoid arthritis
  Lung cancer
  Lung carcinoma
• UniProt ID: BANP_HUMAN
• PDB ID: 7YUG; 7YUK; 8HTX
• Pfam ID: PF10523
• Sequence:
  MMSEHDLADVVQIAVEDLSPDHPVVLENHVVTDEDEPALKRQRLEINCQDPSIKTICLRL
  DSIEAKLQALEATCKSLEEKLDLVTNKQHSPIQVPMVAGSPLGATQTCNKVRCVVPQTTV
  ILNNDRQNAIVAKMEDPLSNRAPDSLENVISNAVPGRRQNTIVVKVPGQEDSHHEDGESG
  SEASDSVSSCGQAGSQSIGSNVTLITLNSEEDYPNGTWLGDENNPEMRVRCAIIPSDMLH
  ISTNCRTAEKMALTLLDYLFHREVQAVSNLSGQGKHGKKQLDPLTIYGIRCHLFYKFGIT
  ESDWYRIKQSIDSKCRTAWRRKQRGQSLAVKSFSRRTPNSSSYCPSEPMMSTPPPASELP
  QPQPQPQALHYALANAQQVQIHQIGEDGQVQVGHLHIAQVPQGEQVQITQDSEGNLQIHH
  VGQDGQLLEATRIPCLLAPSVFKASSGQVLQGAQLIAVASSDPAAAGVDGSPLQGSDIQV
  QYVQLAPVSDHTAGAQTAEALQPTLQPEMQLEHGAIQIQ
• Function: Controls V(D)J recombination during T-cell development by repressing T-cell receptor (TCR) beta enhancer function. Binds to scaffold/matrix attachment region beta (S/MARbeta), an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Represses cyclin D1 transcription by recruiting HDAC1 to its promoter, thereby diminishing H3K9ac, H3S10ph and H4K8ac levels. Promotes TP53 activation, which causes cell cycle arrest.
• Tissue Specificity: Down-regulated in breast cancer cell lines.
• Reactome Pathway: Regulation of TP53 Activity through Association with Co-factors (R-HSA-6804759)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Keratoconus	DISOONXH	Strong	Genetic Variation	[5]
Melanoma	DIS1RRCY	Strong	Altered Expression	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Disputed	Biomarker	[9]
Lung carcinoma	DISTR26C	Disputed	Biomarker	[9]

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 Protein BANP (BANP).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein BANP (BANP).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Protein BANP (BANP).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein BANP (BANP).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein BANP (BANP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein BANP (BANP).	[17]

4 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 Protein BANP (BANP).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein BANP (BANP).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein BANP (BANP).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein BANP (BANP).	[15]

References

• [1] SMAR1 favors immunosurveillance of cancer cells by modulating calnexin and MHC I expression.Neoplasia. 2019 Oct;21(10):945-962. doi: 10.1016/j.neo.2019.07.002. Epub 2019 Aug 15.
• [2] Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases.Indian J Med Res. 2015 Oct;142(4):405-13. doi: 10.4103/0971-5916.169198.
• [3] Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding domain) controls breast tumor in mice model.Nanomedicine (Lond). 2018 Feb;13(4):353-372. doi: 10.2217/nnm-2017-0298. Epub 2018 Jan 17.
• [4] SMAR1 inhibits Wnt/-catenin signaling and prevents colorectal cancer progression.Oncotarget. 2018 Apr 20;9(30):21322-21336. doi: 10.18632/oncotarget.25093. eCollection 2018 Apr 20.
• [5] Evaluating the Association between Keratoconus and Reported Genetic Loci in a Han Chinese Population.Ophthalmic Genet. 2015 Jun;36(2):132-6. doi: 10.3109/13816810.2015.1005317. Epub 2015 Feb 12.
• [6] Direct interaction with and activation of p53 by SMAR1 retards cell-cycle progression at G2/M phase and delays tumor growth in mice.Int J Cancer. 2003 Feb 20;103(5):606-15. doi: 10.1002/ijc.10881.
• [7] p53 target gene SMAR1 is dysregulated in breast cancer: its role in cancer cell migration and invasion.PLoS One. 2007 Aug 1;2(7):e660. doi: 10.1371/journal.pone.0000660.
• [8] SMAR1 promotes immune escape of Tri-negative Breast Cancer through a mechanism involving T-bet/PD-1 Axis.Cell Mol Biol (Noisy-le-grand). 2018 Sep 30;64(12):70-75.
• [9] CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression.Biochem Biophys Res Commun. 2018 Sep 18;503(4):2429-2435. doi: 10.1016/j.bbrc.2018.06.172. Epub 2018 Jul 6.
• [10] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [11] 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.
• [12] 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.
• [13] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] 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.
• [17] 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.