Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1EBTM)

DOT Name FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1)
Synonyms Chondrocyte-derived ezrin-like protein; FERM, RhoGEF and pleckstrin domain-containing protein 1; Pleckstrin homology domain-containing family C member 2; PH domain-containing family C member 2
Gene Name FARP1
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Cutaneous melanoma ( )
Drug dependence ( )
Melanoma ( )
Pheochromocytoma ( )
Schizophrenia ( )
Substance abuse ( )
Substance dependence ( )
Stroke ( )
UniProt ID
FARP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4H6Y
Pfam ID
PF08736 ; PF09380 ; PF00373 ; PF09379 ; PF00169 ; PF00621
Sequence
MGEIEQRPTPGSRLGAPENSGISTLERGQKPPPTPSGKLVSIKIQMLDDTQEAFEVPQRA
PGKVLLDAVCNHLNLVEGDYFGLEFPDHKKITVWLDLLKPIVKQIRRPKHVVVKFVVKFF
PPDHTQLQEELTRYLFALQVKQDLAQGRLTCNDTSAALLISHIVQSEIGDFDEALDREHL
AKNKYIPQQDALEDKIVEFHHNHIGQTPAESDFQLLEIARRLEMYGIRLHPAKDREGTKI
NLAVANTGILVFQGFTKINAFNWAKVRKLSFKRKRFLIKLRPDANSAYQDTLEFLMASRD
FCKSFWKICVEHHAFFRLFEEPKPKPKPVLFSRGSSFRFSGRTQKQVLDYVKEGGHKKVQ
FERKHSKIHSIRSLASQPTELNSEVLEQSQQSTSLTFGEGAESPGGQSCRRGKEPKVSAG
EPGSHPSPAPRRSPAGNKQADGAASAPTEEEEEVVKDRTQQSKPQPPQPSTGSLTGSPHL
SELSVNSQGGVAPANVTLSPNLSPDTKQASPLISPLLNDQACPRTDDEDEGRRKRFPTDK
AYFIAKEVSTTERTYLKDLEVITSWFQSTVSKEDAMPEALKSLIFPNFEPLHKFHTNFLK
EIEQRLALWEGRSNAQIRDYQRIGDVMLKNIQGMKHLAAHLWKHSEALEALENGIKSSRR
LENFCRDFELQKVCYLPLNTFLLRPLHRLMHYKQVLERLCKHHPPSHADFRDCRAALAEI
TEMVAQLHGTMIKMENFQKLHELKKDLIGIDNLVVPGREFIRLGSLSKLSGKGLQQRMFF
LFNDVLLYTSRGLTASNQFKVHGQLPLYGMTIEESEDEWGVPHCLTLRGQRQSIIVAASS
RSEMEKWVEDIQMAIDLAEKSSSPAPEFLASSPPDNKSPDEATAADQESEDDLSASRTSL
ERQAPHRGNTMVHVCWHRNTSVSMVDFSIAVENQLSGNLLRKFKNSNGWQKLWVVFTNFC
LFFYKSHQDNHPLASLPLLGYSLTIPSESENIQKDYVFKLHFKSHVYYFRAESEYTFERW
MEVIRSATSSASRPHVLSHKESLVY
Function
Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses.
Tissue Specificity Detected in cAMP-treated chondrocytes, but not in untreated chondrocytes. Detected in fetal brain, heart and spleen, and in adult testis, kidney and lung.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RHOF GTPase cycle (R-HSA-9035034 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Cutaneous melanoma DIS3MMH9 Strong Altered Expression [1]
Drug dependence DIS9IXRC Strong Biomarker [3]
Melanoma DIS1RRCY Strong Altered Expression [1]
Pheochromocytoma DIS56IFV Strong Altered Expression [4]
Schizophrenia DISSRV2N Strong Genetic Variation [5]
Substance abuse DIS327VW Strong Biomarker [3]
Substance dependence DISDRAAR Strong Biomarker [3]
Stroke DISX6UHX moderate Biomarker [6]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [7]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [16]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [22]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [21]
1,6-hexamethylene diisocyanate DMLB3RT Investigative 1,6-hexamethylene diisocyanate increases the methylation of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [25]
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⏷ Show the Full List of 6 Drug(s)
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [12]
Quercetin DM3NC4M Approved Quercetin decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [13]
Selenium DM25CGV Approved Selenium increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [14]
Menadione DMSJDTY Approved Menadione affects the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [15]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [17]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [18]
Afimoxifene DMFORDT Phase 2 Afimoxifene increases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [23]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of FERM, ARHGEF and pleckstrin domain-containing protein 1 (FARP1). [24]
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⏷ Show the Full List of 14 Drug(s)

References

1 FARP1 Facilitates Cell Proliferation Through Modulating MAPK Signaling Pathway in Cutaneous Melanoma.Am J Dermatopathol. 2019 Dec;41(12):908-913. doi: 10.1097/DAD.0000000000001426.
2 Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
3 Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
4 Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression.Endocr Relat Cancer. 2016 Apr;23(4):281-93. doi: 10.1530/ERC-15-0502. Epub 2016 Feb 24.
5 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
6 Genes from a translational analysis support a multifactorial nature of white matter hyperintensities.Stroke. 2015 Feb;46(2):341-7. doi: 10.1161/STROKEAHA.114.007649. Epub 2015 Jan 13.
7 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.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 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.
13 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.
14 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.
15 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
16 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.
17 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
18 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
19 Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
20 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
21 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.
22 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
23 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.
24 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
25 DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.