Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKA7EZI)

• DOT Name: Fas-binding factor 1 (FBF1)
• Synonyms: FBF-1; Protein albatross
• Gene Name: FBF1
• Related Disease: Coronary heart disease
• UniProt ID: FBF1_HUMAN
• Pfam ID: PF21007
• Sequence:
  MAPKTKKGCKVTLPEKPVKLASHTRDTTGVSQMFPSSKARTKSLLGDDVFSTMAGLEEAD
  AEVSGISEADPQALLQAMKDLDGMDADILGLKKSNSAPSKKAAKDPGKGELPNHPKPAGG
  AIPTKKSLPSPSSSGHQNRRFSSEDLEDPLRGLLSYDEGGITKQPPVTQSKTASDKSPST
  VRDQGPSIPLTPGDTPIRKKEELLFDDGDDIMATLGFGDSPKAEKRQIGDQEGPRPARST
  LDELLGRGMATKLLARPGTGEHREFKLDKKYQRPQDSEDMWGDEDFTFGAYQPTVVSSEG
  RQSRRQSVSRFFADSGADPKGEPGSKQSPPMASSPIQPRKGGADWLGLKDEDLDLFPASP
  TREAHRESSVPVTPSVPPPASQHSTPAGLPPSRAKPPTEGAGSPAKASQASKLRASKEEK
  EDWLSHALSRKKSQGLAREQHAGTSEGLHLAGTAGHPPSGSQPLTSTQGLEHAAAGGSSG
  TTARERPCVRPGVSGSPVTQNHAASALPTGSPKRGTAPGDLSATEPATCFPSTQKPTEPS
  VPVQPLLPESLARSLLPSTEYQKQLLAAQVQLQCSPAELQAELLHSQARLAELEAQVRKL
  ELERAQHELLLGSLQQQHQADLELIESAHRSRIKVLETSYQQREERLRRENEELSARYLS
  QCQEAEQARAELTAQHQRRLAAIAQEKDQEMERLRELQRASILDMRRDHEEQLQRLKLLK
  DREVDAATSATSHTRSLNSIIHQMEKFSSSLHELSSRVEASHLTTSQERELGIRQRDEQL
  RALQERLGQQQRDMEEERSRQQEVIGKMEARLNEQSRLLEQERWRVTAEQSKAESMQRAL
  EEQRKVTAQQMAMERAELERAKSALLEEQKSVMLKCGEERRRLAAEWAEFSAQQKLSKER
  AEREAERALQVDTQREGTLISLAKQAELKIRASELRAEEKQLAAERAALEQERQELRLEK
  ERINATALRVKLRAEEVESMSKVASEKYEEGERALREAQQVQAEQQARLQAVQQQQERLR
  KQEQHMHQEHLSLAQQRLQLDRARQDLPSSLVGLFPRAQGPAASSQSALMPPAPTTRWCS
  QPPTGLDPSPLHLHARLALLRHMAEQDRDFLENEQFFLETLKKGSYNLTSHSA
• Function: Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
• Tissue Specificity: Present in various epithelial cells (at protein level).
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[1]

4 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 Fas-binding factor 1 (FBF1).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fas-binding factor 1 (FBF1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fas-binding factor 1 (FBF1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Fas-binding factor 1 (FBF1).	[7]

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 Fas-binding factor 1 (FBF1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Fas-binding factor 1 (FBF1).	[5]

References

• [1] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] 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.
• [4] 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.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] 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.
• [7] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.