Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV1UBCS)

DOT Name Formin-binding protein 4 (FNBP4)
Synonyms Formin-binding protein 30
Gene Name FNBP4
Related Disease
Microphthalmia with limb anomalies ( )
Venous thromboembolism ( )
UniProt ID
FNBP4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00397
Sequence
MGKKSRAVPGRRPILQLSPPGPRGSTPGRDPEPEPDTEPDSTAAVPSQPAPSAATTTTTA
VTAAAASDDSPSEDEQEAVQEVPRVVQNPPKPVMTTRPTAVKATGGLCLLGAYADSDDDD
NDVSEKLAQSKETNGNQSTDIDSTLANFLAEIDAITAPQPAAPVGASAPPPTPPRPEPKE
AATSTLSSSTSNGTDSTQTSGWQYDTQCSLAGVGIEMGDWQEVWDENTGCYYYWNTQTNE
VTWELPQYLATQVQGLQHYQPSSVPGAETSFVVNTDIYSKEKTISVSSSKSGPVIAKREV
KKEVNEGIQALSNSEEEKKGVAASLLAPLLPEGIKEEEERWRRKVICKEEPVSEVKETST
TVEEATTIVKPQEIMLDNIEDPSQEDLCSVVQSGESEEEEEQDTLELELVLERKKAELRA
LEEGDGSVSGSSPRSDISQPASQDGMRRLMSKRGKWKMFVRATSPESTSRSSSKTGRDTP
ENGETAIGAENSEKIDENSDKEMEVEESPEKIKVQTTPKVEEEQDLKFQIGELANTLTSK
FEFLGINRQSISNFHVLLLQTETRIADWREGALNGNYLKRKLQDAAEQLKQYEINATPKG
WSCHWDRDHRRYFYVNEQSGESQWEFPDGEEEEEESQAQENRDETLAKQTLKDKTGTDSN
STESSETSTGSLCKESFSGQVSSSSLMPLTPFWTLLQSNVPVLQPPLPLEMPPPPPPPPE
SPPPPPPPPPPAEDGEIQEVEMEDEGSEEPPAPGTEEDTPLKPSAQTTVVTSQSSVDSTI
SSSSSTKGIKRKATEISTAVVQRSATIGSSPVLYSQSAIATGHQAAGIGNQATGIGHQTI
PVSLPAAGMGHQARGMSLQSNYLGLAAAPAIMSYAECSVPIGVTAPSLQPVQARGAVPTA
TIIEPPPPPPPPPPPPPPAPKMPPPEKTKKGRKDKAKKSKTKMPSLVKKWQSIQRELDEE
DNSSSSEEDRESTAQKRIEEWKQQQLVSGMAERNANFEALPEDWRARLKRRKMAPNT
Tissue Specificity Highly expressed in the eye.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Microphthalmia with limb anomalies DIS19E4H Strong Genetic Variation [1]
Venous thromboembolism DISUR7CR Strong Genetic Variation [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Chlorpyrifos DMKPUI6 Investigative Formin-binding protein 4 (FNBP4) decreases the response to substance of Chlorpyrifos. [22]
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15 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 Formin-binding protein 4 (FNBP4). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Formin-binding protein 4 (FNBP4). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Formin-binding protein 4 (FNBP4). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Formin-binding protein 4 (FNBP4). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Formin-binding protein 4 (FNBP4). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Formin-binding protein 4 (FNBP4). [8]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Formin-binding protein 4 (FNBP4). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Formin-binding protein 4 (FNBP4). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Formin-binding protein 4 (FNBP4). [12]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Formin-binding protein 4 (FNBP4). [13]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Formin-binding protein 4 (FNBP4). [14]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Formin-binding protein 4 (FNBP4). [15]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Formin-binding protein 4 (FNBP4). [17]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Formin-binding protein 4 (FNBP4). [20]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Formin-binding protein 4 (FNBP4). [21]
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⏷ Show the Full List of 15 Drug(s)
6 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Formin-binding protein 4 (FNBP4). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Formin-binding protein 4 (FNBP4). [16]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Formin-binding protein 4 (FNBP4). [18]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Formin-binding protein 4 (FNBP4). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Formin-binding protein 4 (FNBP4). [19]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Formin-binding protein 4 (FNBP4). [9]
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⏷ Show the Full List of 6 Drug(s)

References

1 Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies.Am J Med Genet A. 2013 Jul;161A(7):1543-6. doi: 10.1002/ajmg.a.35983. Epub 2013 May 23.
2 Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
9 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
10 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.
11 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.
12 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
13 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.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
15 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
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 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
18 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.
19 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.
20 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
21 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
22 Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study. J Pharmacol Toxicol Methods. 2015 Nov-Dec;76:76-82. doi: 10.1016/j.vascn.2015.08.154. Epub 2015 Aug 20.