Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJSJOC5)

• DOT Name: Izumo sperm-egg fusion protein 1 (IZUMO1)
• Synonyms: Oocyte binding/fusion factor; OBF; Sperm-specific protein izumo
• Gene Name: IZUMO1
• Related Disease:
  Male infertility
  Oligospermia
• UniProt ID: IZUM1_HUMAN
• PDB ID: 5F4E; 5F4T; 5F4V; 5JK9; 5JKC; 5JKD; 5JKE
• Pfam ID: PF15005 ; PF16706
• Sequence:
  MGPHFTLLCAALAGCLLPAEGCVICDPSVVLALKSLEKDYLPGHLDAKHHKAMMERVENA
  VKDFQELSLNEDAYMGVVDEATLQKGSWSLLKDLKRITDSDVKGDLFVKELFWMLHLQKE
  TFATYVARFQKEAYCPNKCGVMLQTLIWCKNCKKEVHACRKSYDCGERNVEVPQMEDMIL
  DCELNWHQASEGLTDYSFYRVWGNNTETLVSKGKEATLTKPMVGPEDAGSYRCELGSVNS
  SPATIINFHVTVLPKMIKEEKPSPNIVTPGEATTESSISLQPLQPEKMLASRLLGLLICG
  SLALITGLTFAIFRRRKVIDFIKSSLFGLGSGAAEQTQVPKEKATDSRQQ
• Function: Essential sperm cell-surface protein required for fertilization by acting as a ligand for IZUMO1R/JUNO receptor on egg. The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion. The ligand-receptor interaction probably does not act as a membrane 'fusogen'. Acts a ligand for the human-specific oolemma epitope FCRL3/MAIA during fertilization. FCRL3/MAIA replaces IZUMO1R/JUNO as IZUMO1 receptor after sperm-egg adhesion, which permits species-specific gamete fusion.
• Tissue Specificity: Sperm-specific (at protein level) . Detectable on sperm surface only after the acrosome reaction .
• Reactome Pathway: Acrosome Reaction and Sperm (R-HSA-1300645)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]
Oligospermia	DIS6YJF3	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Izumo sperm-egg fusion protein 1 (IZUMO1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Izumo sperm-egg fusion protein 1 (IZUMO1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Izumo sperm-egg fusion protein 1 (IZUMO1).	[4]

References

• [1] Male infertility-related molecules involved in sperm-oocyte fusion.J Reprod Dev. 2017 Feb 16;63(1):1-7. doi: 10.1262/jrd.2016-108. Epub 2016 Dec 1.
• [2] Positive expression of the immunoglobulin superfamily protein IZUMO on human sperm of severely infertile male patients.Fertil Steril. 2007 Jul;88(1):214-6. doi: 10.1016/j.fertnstert.2006.11.086. Epub 2007 Feb 12.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.