IZUMO1 notes

Deep research (just deep-research-falcon human IZUMO1 --fallback perplexity-lite) failed in this
environment (no agentapi / perplexity provider). Research done directly from cached publications and
the UniProt record.

Identity

• UniProt Q8IYV9, IZUMO1; Izumo family (IZUMO domain helical bundle + Ig-like domain), single-pass type I
  membrane protein, sperm-specific.

Function

• Mouse knockout: males sterile; sperm bind and penetrate the zona pellucida but cannot fuse with eggs
  PMID:15759005.
  Antibody to human Izumo blocks fusion of human sperm with zona-free hamster eggs
  PMID:15759005.
• Egg receptor is JUNO (IZUMO1R/FOLR4); interaction is conserved in humans
  PMID:24739963.
• Crystal structure of human IZUMO1-JUNO complex; beta-hairpin is the JUNO-binding platform
  PMID:27309808.
• Human oolemmal FCRL3/MAIA interacts with IZUMO1/JUNO complex
  PMID:36070373.
• IZUMO1-SPACA6-TMEM81 trimeric sperm complex, human orthologs interact in vitro
  PMID:39423812.
• IZUMO1-JUNO is an adhesion step; IZUMO1 is not established as the fusogen (UniProt: "The ligand-receptor
  interaction probably does not act as a membrane 'fusogen'").

Localization

• Initially in acrosomal membranes (inner and outer) of sperm head; exposed on sperm plasma membrane surface
  only after the acrosome reaction, relocating to the equatorial segment (UniProt; PMID:15759005; PMID:36070373).
• ER retention via FREY during spermatogenesis (mouse, UniProt by similarity) -- biosynthetic transit.
• Conclusion: plasma membrane (post-acrosome-reaction sperm), extracellular domain exposed; resident in
  acrosomal membrane before acrosome reaction. Not on surface of non-acrosome-reacted sperm.

Curation decisions

• Zona pellucida binding (IBA/IEA, rat donor): contradicted by mouse KO phenotype (ZP binding normal) -> REMOVE.
• receptor ligand activity / signal transduction: JUNO is a GPI-anchored receptor with no shown signaling
  output; IZUMO1 is an adhesion molecule. Over-annotation; signal transduction IEA removed.