Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJ8HSD)

• DOT Name: Protein FRG1 (FRG1)
• Synonyms: FSHD region gene 1 protein
• Gene Name: FRG1
• Related Disease:
  Advanced cancer
  Crohn disease
  Myopathy
  Neuromuscular disease
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Muscular dystrophy
• UniProt ID: FRG1_HUMAN
• PDB ID: 6ZYM; 7A5P
• Pfam ID: PF06229
• Sequence:
  MAEYSYVKSTKLVLKGTKTKSKKKKSKDKKRKREEDEETQLDIVGIWWTVTNFGEISGTI
  AIEMDKGTYIHALDNGLFTLGAPHKEVDEGPSPPEQFTAVKLSDSRIALKSGYGKYLGIN
  SDGLVVGRSDAIGPREQWEPVFQNGKMALLASNSCFIRCNEAGDIEAKSKTAGEEEMIKI
  RSCAERETKKKDDIPEEDKGNVKQCEINYVKKFQSFQDHKLKISKEDSKILKKARKDGFL
  HETLLDRRAKLKADRYCK
• Function: Binds to mRNA in a sequence-independent manner. May play a role in regulation of pre-mRNA splicing or in the assembly of rRNA into ribosomal subunits. May be involved in mRNA transport. May be involved in epigenetic regulation of muscle differentiation through regulation of activity of the histone-lysine N-methyltransferase KMT5B.
• Tissue Specificity: Expressed in adult muscle, lymphocytes, fetal brain, muscle, and placenta. Also expressed in the smooth muscle of arteries and veins, the sweat glands and the epidermis.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[2]
Myopathy	DISOWG27	Strong	Biomarker	[3]
Neuromuscular disease	DISQTIJZ	Strong	Biomarker	[4]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Muscular dystrophy	DISJD6P7	moderate	Biomarker	[6]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein FRG1 (FRG1).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein FRG1 (FRG1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FRG1 (FRG1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FRG1 (FRG1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FRG1 (FRG1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein FRG1 (FRG1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein FRG1 (FRG1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FRG1 (FRG1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein FRG1 (FRG1).	[15]

References

• [1] Whole-Exome Sequencing Identifies Two Discrete Druggable Signaling Pathways in Follicular Thyroid Cancer.J Am Coll Surg. 2018 Jun;226(6):950-959.e5. doi: 10.1016/j.jamcollsurg.2018.01.059. Epub 2018 Mar 20.
• [2] Cryptic 13q34 and 4q35.2 Deletions in an Italian Family.Cytogenet Genome Res. 2015;147(1):24-30. doi: 10.1159/000442068. Epub 2015 Dec 9.
• [3] RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1).Mol Ther. 2011 Nov;19(11):2048-54. doi: 10.1038/mt.2011.118. Epub 2011 Jul 5.
• [4] FRG1P-mediated aggregation of proteins involved in pre-mRNA processing.Chromosoma. 2007 Feb;116(1):53-64. doi: 10.1007/s00412-006-0083-3. Epub 2006 Nov 14.
• [5] Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion.BMC Cancer. 2019 Apr 11;19(1):346. doi: 10.1186/s12885-019-5509-4.
• [6] Muscular dystrophy candidate gene FRG1 is critical for muscle development.Dev Dyn. 2009 Jun;238(6):1502-12. doi: 10.1002/dvdy.21830.
• [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] 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.
• [10] 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.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.