Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTBG0V7)

DOT Name	Bifunctional apoptosis regulator (BFAR)
Synonyms	RING finger protein 47
Gene Name	BFAR
Related Disease	Neoplasm ( ) Advanced cancer ( ) Barrett esophagus ( ) Bipolar disorder ( ) Cardiac failure ( ) Congestive heart failure ( ) Erythema multiforme ( ) Esophageal adenocarcinoma ( ) Myocardial infarction ( ) Non-insulin dependent diabetes ( ) Oculocerebrorenal syndrome ( ) Schizophrenia ( ) Peripheral arterial disease ( ) Peripheral vascular disease ( ) Small lymphocytic lymphoma ( ) Metabolic disorder ( ) Inflammation ( ) Intellectual disability ( ) Periodontitis ( )
UniProt ID	BFAR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00536 ; PF15227
Sequence	MEEPQKSYVNTMDLERDEPLKSTGPQISVSEFSCHCCYDILVNPTTLNCGHSFCRHCLAL WWASSKKTECPECREKWEGFPKVSILLRDAIEKLFPDAIRLRFEDIQQNNDIVQSLAAFQ KYGNDQIPLAPNTGRANQQMGGGFFSGVLTALTGVAVVLLVYHWSSRESEHDLLVHKAVA KWTAEEVVLWLEQLGPWASLYRERFLSERVNGRLLLTLTEEEFSKTPYTIENSSHRRAIL MELERVKALGVKPPQNLWEYKAVNPGRSLFLLYALKSSPRLSLLYLYLFDYTDTFLPFIH TICPLQEDSSGEDIVTKLLDLKEPTWKQWREFLVKYSFLPYQLIAEFAWDWLEVHYWTSR FLIINAMLLSVLELFSFWRIWSRSELKTVPQRMWSHFWKVSTQGLFVAMFWPLIPQFVCN CLFYWALYFNPIINIDLVVKELRRLETQVL
Function	Apoptosis regulator. Has anti-apoptotic activity, both for apoptosis triggered via death-receptors and via mitochondrial factors.
Tissue Specificity	Expressed highly in brain, moderately in small intestine, weakly in testes and only faintly in liver and skeletal muscle. Not expressed in heart, kidney, lung and spleen.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[4]
Cardiac failure	DISDC067	Strong	Altered Expression	[5]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[5]
Erythema multiforme	DISKCLM1	Strong	Biomarker	[6]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[7]
Myocardial infarction	DIS655KI	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[8]
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Biomarker	[10]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[11]
Peripheral vascular disease	DISXSU1Y	moderate	Biomarker	[11]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[12]
Metabolic disorder	DIS71G5H	Disputed	Genetic Variation	[13]
Inflammation	DISJUQ5T	Limited	Biomarker	[14]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[15]
Periodontitis	DISI9JOI	Limited	Biomarker	[16]
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⏷ Show the Full List of 19 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bifunctional apoptosis regulator (BFAR).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Bifunctional apoptosis regulator (BFAR).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Bifunctional apoptosis regulator (BFAR).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Bifunctional apoptosis regulator (BFAR).	[20]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Bifunctional apoptosis regulator (BFAR).	[21]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Bifunctional apoptosis regulator (BFAR).	[22]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Bifunctional apoptosis regulator (BFAR).	[23]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Bifunctional apoptosis regulator (BFAR).	[24]
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⏷ Show the Full List of 8 Drug(s)

References

1	Transformation of benign Barrett's epithelium by repeated acid and bile exposure over 65 weeks: a novel in vitro model.Int J Cancer. 2011 Jan 15;128(2):274-82. doi: 10.1002/ijc.25343. Epub 2010 Mar 22.
2	Identification of a novel effector domain of BIN1 for cancer suppression.J Cell Biochem. 2011 Oct;112(10):2992-3001. doi: 10.1002/jcb.23222.
3	Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett's Cells.Gastroenterology. 2019 Jan;156(1):130-144.e10. doi: 10.1053/j.gastro.2018.09.046. Epub 2018 Sep 27.
4	A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults.J Affect Disord. 2010 Dec;127(1-3):316-20. doi: 10.1016/j.jad.2010.06.016. Epub 2010 Jul 8.
5	Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure.Sci Rep. 2019 May 1;9(1):6801. doi: 10.1038/s41598-019-42592-1.
6	Outcome after new generation single-layer polytetrafluoroethylene-covered stent implantation for the treatment of coronary artery perforation.Catheter Cardiovasc Interv. 2019 Apr 1;93(5):912-920. doi: 10.1002/ccd.27979. Epub 2018 Nov 23.
7	Role of NADPH oxidase NOX5-S, NF-B, and DNMT1 in acid-induced p16 hypermethylation in Barrett's cells.Am J Physiol Cell Physiol. 2013 Nov 15;305(10):C1069-79. doi: 10.1152/ajpcell.00080.2013. Epub 2013 Sep 11.
8	Do genetic variations alter the effects of exercise training on cardiovascular disease and can we identify the candidate variants now or in the future?.J Appl Physiol (1985). 2011 Sep;111(3):916-28. doi: 10.1152/japplphysiol.00153.2011. Epub 2011 May 12.
9	IPIP27 Coordinates PtdIns(4,5)P(2) Homeostasis for Successful Cytokinesis.Curr Biol. 2019 Mar 4;29(5):775-789.e7. doi: 10.1016/j.cub.2019.01.043. Epub 2019 Feb 21.
10	Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis.Mol Brain. 2016 May 18;9(1):54. doi: 10.1186/s13041-016-0238-y.
11	A prospective, multi-center study of the chocolate balloon in femoropopliteal peripheral artery disease: The Chocolate BAR registry.Catheter Cardiovasc Interv. 2018 May 1;91(6):1144-1148. doi: 10.1002/ccd.27565. Epub 2018 Mar 7.
12	CIP4 controls CCL19-driven cell steering and chemotaxis in chronic lymphocytic leukemia.Cancer Res. 2013 Jun 1;73(11):3412-24. doi: 10.1158/0008-5472.CAN-12-3564. Epub 2013 May 3.
13	The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population-based Caucasian cohort.J Clin Endocrinol Metab. 1998 Aug;83(8):2892-7. doi: 10.1210/jcem.83.8.5004.
14	Antagonistic regulation of F-BAR protein assemblies controls actin polymerization during podosome formation.J Cell Sci. 2013 May 15;126(Pt 10):2267-78. doi: 10.1242/jcs.122515. Epub 2013 Mar 22.
15	A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with intellectual disability and hippocampal alterations.Eur J Hum Genet. 2014 May;22(5):644-51. doi: 10.1038/ejhg.2013.216. Epub 2013 Oct 9.
16	BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis-Streptococcus gordonii biofilms.J Nanobiotechnology. 2018 Sep 15;16(1):69. doi: 10.1186/s12951-018-0396-4.
17	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.
18	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
19	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
20	Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
21	Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916-24. doi: 10.1093/carcin/bgi312. Epub 2005 Dec 16.
22	Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
23	Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
24	Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.