The characterization of pregnancy associated plasma protein-E and the identification of an alternative splice variant.

We have performed differential display and bioinformatic database mining of the placenta, in an attempt to find novel diagnostic markers of pathological pregnancies. We have identified a full-length cDNA encoding the preproprotein of pregnancy associated plasma protein-E (PAPP-E); a putative metalloprotease, of 1790-residues with a putative 21-residue signal peptide. An alternatively spliced mRNA was found to encode an 826-residue precursor protein corresponding to the N-terminus of PAPP-E. Both PAPP-E variants were found to be co-expressed abundantly in the placenta and non-pregnant mammary gland with low expression in the kidney, foetal brain and pancreas. Analysis of the predicted proteins suggests that the longer variant be targeted to the nucleus while the shorter variant is secreted extracellularly. Gene structure analysis revealed that PAPP-E was encoded on 23 exons on chromosome 1 and its splice variant on the first five same exons. The discovery of the PAPP-E variants will help in the deciphering of the physiology of this new family of metzincins in not only the placenta during pregnancy but also the mammary gland in breast cancer. The new PAPP-E variants could have the potential for the diagnosis of pathological pregnancies including trisomies such as Down's syndrome. Copyright 2001 Harcourt Publishers Ltd.