Disease relevance of PAPPA2

• 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 [1].
• The new PAPP-E variants could have the potential for the diagnosis of pathological pregnancies including trisomies such as Down's syndrome [1].

High impact information on PAPPA2

• Except for PAPP-A2, PAPP-A does not share global similarity with other proteins [2].
• We showed that PAPP-A2 specifically cleaved IGFBP-5 at one site, between Ser-143 and Lys-144 [3].
• Because PAPP-A specifically cleaves insulin-like growth factor-binding protein (IGFBP)-4, one of six known modulators of IGF-I and -II, we looked for a possible PAPP-A2 substrate among the members of this family [3].
• This explains, at least in part, why PAPP-A2 lacks the ability of cell surface adhesion, and further emphasizes the role of the basic clusters defined in PAPP-A [4].
• In addition, new alternative spliced mRNAs were detected for IK, TRAP240 and PLAC3 genes [5].

Biological context of PAPPA2

• 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 [1].
• The PAPP-E gene was localized to chromosome 1q23-25 [6].
• We present evidence that a protein domain with weak similarity to known laminin G-like (LG) modules is contained within this region, and we propose that PAPP-A and PAPP-A2 are new and unique members in the group of LG proteins as the pappalysins represent the first examples where LG modules are associated with proteinases [7].

Anatomical context of PAPPA2

• 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 [1].

Other interactions of PAPPA2

• Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase [3].
• This finding allowed further mapping of the PAPP-A adhesion site to short consensus repeat modules 3 and 4 by the expression and analysis of nine PAPP-A/PAPP-A2 chimeras [8].

Analytical, diagnostic and therapeutic context of PAPPA2

• Northern blot analysis showed that PAPP-E is predominantly expressed in placenta [6].

References