The present invention provides nucleotide and amino acid sequences that identify and encode a new protein with homology to pregnancy-associated plasma protein-A (PAPP-A). We denote this protein PAPP-A2. The cDNA encoding PAPP-A2 was derived from human placenta. The present invention also provides for antisense molecules to the nucleotide sequences which encode PAPP-A2, expression vectors for the production of purified PAPP-A2, antibodies capable of binding specifically to PAPP-A2, hybridization probes or oligonucleotides for the detection of PAPP-A2-encoding nucleotide sequences, genetically engineered host cells for the expression of PAPP-A2, use of the protein to produce antibodies capable of binding specifically to the protein, methods for screening for pathologies in pregnant and non-pregnant patients that are based on detection of PAPP-A2 antigen in human body fluids or PAPP-A2-encoding nucleic acid molecules, use of the protein to screen for agents that alter the protease activity of PAPP-A2, use of the protein as a therapeutic target for such agents, and use of the protein as a therapeutic agent in relevant pathological states. Methods for screening for altered focal proliferation states in pregnant and/or non-pregnant patients, which include detecting levels of PAPP-A2, are also described. The present invention also provides the identification of a natural substrate of PAPP-A2, insulin-like growth factor binding protein (IGFBP)-5.
