ZP2

Zona pellucida sperm-binding protein 2 is a is_associated_with::protein that in humans is encoded by the ZP2 is_associated_with::gene.

Function
The is_associated_with::zona pellucida is an extracellular matrix that surrounds the is_associated_with::oocyte and early embryo. It is composed primarily of three (mouse) or four (human) is_associated_with::glycoproteins (ZP1-4) with various functions during fertilization and preimplantation development. The protein encoded by this gene is a structural component of the zona pellucida and functions in secondary binding and penetration of is_associated_with::acrosome-reacted is_associated_with::spermatozoa. The nascent protein contains a is_associated_with::N-terminal is_associated_with::signal peptide sequence, a conserved ZP domain, a consensus is_associated_with::furin cleavage site, and a is_associated_with::C-terminal transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies.

The sperm-binding domain on the ZP2 protein is necessary in both humans and mice for oocyte-sperm recognition and penetration of the zona pellucida. It is also responsible for the primary block to polyspermy in mammals. The oocyte has cortical granules peripherally located under the cortex that contain a proteolytic protein called ovastacin. After the sperm binds to ZP2, the cortical granules are exocytosed releasing ovastacin into the is_associated_with::perivitelline space. Ovastacin cleaves ZP2 at the N terminus, preventing more sperm from binding and penetrating the oocyte, thus hardening the zona pellucida. Ovastacin is only found in oocytes, and is part of the astcain family of metalloendoproteases. Female mice engineered without ovastacin showed that ZP2 was not cleaved after fertilization.