Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHMXVN7)

• DOT Name: Protein Frey 1 (FREY1)
• Synonyms: Frey regulator of sperm-oocyte fusion 1; FREY1
• Gene Name: FREY1
• UniProt ID: FREY_HUMAN
• Pfam ID: PF15878
• Sequence:
  MVLAMLGALHPRAGLSLFLHLILAVALLRSQPLRSQRSVPEAFSAPLELSQPLSGLVDDY
  GILPKHPRPRGPRPLLSRAQQRKRDGPDLAEYYYDAHL
• Function: Key regulator for male fertility expressed transiently in round spermatids where it recruits IZUMO1 at the endoplasmic reticulum (ER) membrane and coordinates the oolemmal binding multimeric complex (IZUMO1 complex) assembly. Upon complete assembly of the IZUMO1 complex, its ER retention is released, facilitating IZUMO1 complex export to the acrosome. Through the interaction with SPPL2C, inhibits its intramembrane protease activity directly accessing the catalytic center of an I-CLiP.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Protein Frey 1 (FREY1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein Frey 1 (FREY1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein Frey 1 (FREY1).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein Frey 1 (FREY1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein Frey 1 (FREY1).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein Frey 1 (FREY1).	[6]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.