Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4BPXGG)

• DOT Name: Fibrosin-1-like protein (FBRSL1)
• Synonyms: AUTS2-like protein; HBV X-transactivated gene 9 protein; HBV XAg-transactivated protein 9
• Gene Name: FBRSL1
• Related Disease:
  Atrial fibrillation
  Familial prostate carcinoma
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Coronary heart disease
  Familial atrial fibrillation
  Melanoma
• UniProt ID: FBSL_HUMAN
• Pfam ID: PF15336
• Sequence:
  MEAKVRPSRRSRAQRDRGRRREAARDARAQSPSSGDEPEPSPGKENAGLRGAPPRGAAPA
  PRTARPPRRRRRESSSQEEEVIDGFAIASFSTLEALEKDMALKPHERKEKWERRLIKKPR
  ESETCPPAEPSENRRPLEAGSPGQDLEPACDGARKVPLQPSKQMKVTVSKGGDRDSDDDS
  VLEATSSRDPLSDSSAHAVSGRGYSCDSESGPDDKASVGSEKLFAPGTDKGPALEKSEAK
  AGPVPKVSGLERSRELSAESFLPTASPAPHAAPCPGPPPGSRANPLVKKEPPAPHRHTPQ
  PPPPQPRGLLPTHVPASLGAFAGHSQAAANGLHGLSRSSSAPLGLGKHVSLSPHGPGPHL
  STSHLALRSQAQHQLHAAMFAAPPTLPPPPALPASSLVLPGHPADHELLRQELNTRFLVQ
  SAERPGASLGPGALLRAEFHQHQHTHQHTHQHTHQHQHTFAPFPAGLPPTPPAAPPPFDK
  YAPKLDSPYFRHSSVSFFPSFPPAIPGLPTLLPHPGPFGSLQGAFQPKVSDPYRAVVKVS
  TCWEGPWQGRTLVPPGRPRGARDSRSLQKTWVGVAPAPLSASILSQKPGRWCAVHVQIAW
  QIYRHQQKIKEMQLDPHKLEVGAKLDLFGRPPAPGVFAGFHYPQDLARPLFPSTGAAHPA
  SNPFGPSAHPGSFLPTGPLTDPFSRPSTFGGLGSLSSHAFGGLGSHALAPGGSIFAPKEG
  SSVHGLPSPHEAWNRLHRAPPSFPAPPPWPKSVDAERVSALTNHDREPDNGKEEQERDLL
  EKTRLLSRASPATPAGHPVSGLLLRAQSELGRSGAPAEREAEPRVKESRSPAKEEAAKMP
  ARASPPHSKAAPGDVKVKEERGEDEASEPPAGGLHPAPLQLGLGRERLGAPGFAWEPFRG
  LELPRRAFPAAAPAPGSAALLEPPERPYRDREPHGYSPERLRGELERARAPHLPPAAPAL
  DGALLPSLGALHFPRLSPAALHNGLLARTPPAAAALGAPPPLVTAAGPPTPPGPPRSRTT
  PLGGLGPGEARDYSPSRNPPEVEAR
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[2]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[3]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[1]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[4]

5 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 Fibrosin-1-like protein (FBRSL1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fibrosin-1-like protein (FBRSL1).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Fibrosin-1-like protein (FBRSL1).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Fibrosin-1-like protein (FBRSL1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fibrosin-1-like protein (FBRSL1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fibrosin-1-like protein (FBRSL1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibrosin-1-like protein (FBRSL1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibrosin-1-like protein (FBRSL1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fibrosin-1-like protein (FBRSL1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fibrosin-1-like protein (FBRSL1).	[13]

References

• [1] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [2] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [3] Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease.Circ Genom Precis Med. 2018 Dec;11(12):e002239. doi: 10.1161/CIRCGEN.118.002239.
• [4] DNA repair variants, indoor tanning, and risk of melanoma.Pigment Cell Melanoma Res. 2013 Sep;26(5):677-84. doi: 10.1111/pcmr.12117. Epub 2013 Jun 3.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] 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.