Table I.

Molecular and Immunobiological Characteristics of Izumo Protein

1. Discovery	2. Molecular parameters	3. Utility in CV	4. Human Application
• Discovered using OBF13 monoclonal antibody, and reactive protein was designated as Izumo (Izumo1) after Japanese shrine dedicated to marriage	• It is a sperm-specific 377 amino acid transmembrane glycoprotein with large extracellular region, a single transmembrane region, and a short cytoplasmic tail	• Sperm-specific; not expressed in somatic cells	• Human Izumo cDNA sequence is available at NCBIb
		• Involvement in fertility	• Human sperm extract has Izumo protein band of ∼32.7 kDa
		• Knockout mice have a total block of fertility due to sperm not binding/fusing with oolemma	• Infertile, and not fertile, women have antibodies to Izumo protein
• In mice, four Izumo proteins have been discovered having Izumo domain	• Izumo is a novel member of the immunoglobulin superfamily	• Antibodies to Izumo prevent sperm–oocyte membrane interaction
• Izumo domain seems to be evolutionarily conserved among several mammalian species, including humans	• Although a glycoprotein, its functional activity resides in protein moiety	• Vaccination with Izumo peptide/cDNA causes a long-term, reversible contraceptive effect in mice
	• Protein domain involved in function is present in 319 amino acid extracellular region at N-terminus
	• Mouse Izumo shows a protein band of ∼56 kDa in SDS-PAGEa
	• Not present on sperm surface, but becomes accessible on surface after acrosome reaction

^aSDS-PAGE, sodium-dodecyl sulfate-polyacrylamide gel electrophoresis.

^bNCBI, National Center for Biotechnology Information.