| YWK-II protein is a type I sperm membrane protein which is initially identified as the target antigen to a monoclonal antibody (mAb) raised against proteins extracted from human sperm and is found to localize on the equatorial sector of human sperm head. The coding cDNA is isolated and its deduced polypeptide, designated the YWK-II protein, contains a segment with high homology (70.6%) to the transmembrane-cytoplasmic region of the Amyloid Protein Precursor (APP). The protein is subsequently referred to as the human placenta amyloid precursor protein homologue (APPH) and more similar to rat amyloid precursor like- protein 2 (APLP2), which are apparently species-specific forms of the same component. The human homologous gene coding YWK-II protein/APLP2 is located on chromosome locus 11q24-25 and transcripted ubiquitously in various tissues. The full length cDNA of the human homologous gene is obtained and named as HSD-2 (Genbank Number AF168956). It is 3654bp in length and contains an open reading frame of 763 amino acids. A series of previous experimental results indicate that YWK-II protein/APLP2 is involved in sperm-egg interaction. YWK-II mAb agglutinates human, rat and mouse sperm and prevents heterogamete fertilization. Passive immunization of female mice with YWK-II mAb causes a significant reduction in the number of zygotes formed compared with controls. Additionally, immunization with a polypeptide corresponding to segment 594-610/763 of rat YWK-II protein/APLP2 effectively reduces fertility in both male and female mice. In addition, a more confirmative experiment by using knockout mice demonstrates that mice with a single gene deletion, either APP(-/-) or APLP2(-/-), remain fertile, whereas mice with both gene deletions become infertile. These studies indicate that APP and YWK-II protein/APLP2 are able to compensate for each other functionally and play a...
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