Identification of a new aspartic proteinase expressed by the outer chorionic cell layer of the equine placenta

The pregnancy-associated glycoproteins (PAGs) are placental antigens that w ere initially characterized as pregnancy markers in the maternal circulatio n of domestic ruminant species. They are members of the aspartic proteinase gene family having greatest sequence identity with pepsinogens. However, s ome are not capable of functioning as enzymes. The PAGs are associated with a large gene family within the Artiodactyla order (cattle, camels, pigs). So far, no members of this family have been characterized in species outsid e this order. This report describes the cloning and initial characterizatio n of a PAG-like protein (equine PAG or ePAG) expressed in the placenta of t he horse and zebra (order Perrisodactyla). Equine PAG is a proteinase capab le of degrading C-14-hemoglobin and catalyzing the removal of its own pro-p eptide. The ePAG mRNA is restricted to the chorion both prior to implantati on and in the term placenta. Equine PAG is secreted from cultured placental tissue as both a processed (mature) and unprocessed (zymogen) form. Equine PAG shares similar identity with the PAGs and pepsinogens and probably aro se from a pepsinogen-like precursor that gained the ability to be expressed in the placenta. The promoter of the ePAG gene shares sequence identity wi th the promoter from a bovine PAG gene but not with promoters of other aspa rtic proteinases. Therefore, we hypothesize that ePAG is a remnant of the p epsinogen-like progenitor gene that was expanded within the Artiodactyla to create the large and highly diverse PAG family.