PAPPA - Pregnancy Associated Plasma Protein /Pappalysin | Elisa - Clia - Antibody - Protein

Background:

Pappalysin-1 (PAPP-A) and Pappalysin-2 (PAPP-A2) are both important proteins in the PAPP-A family with roles in the regulation of IGF signaling. While PAPP-A is primarily associated with pregnancy , PAPP-A2 has broader tissue expression and is implicated in postnatal growth and skeletal development. Their distinct functions and tissue expressions contribute to their unique roles in human growth and development. Pappalysin-1 (PAPP-A), Iplays a crucial role in the regulation of insulin-like growth factor (IGF) signaling. Promotes the availability of IGFs, which are essential for fetal growth and development. PAPP-A levels are used as a marker in prenatal screening tests for Down syndrome.Low levels of PAPP-A in maternal blood during the first trimester can indicate an increased risk of chromosomal abnormalities in the fetus.Pappalysin-2 or PAPP-A2 is expressed in various tissues, including the liver, heart, kidney, and placenta. PAPP-A2 has been implicated in postnatal growth regulation, particularly during childhood and adolescence. It has been studied for its role in bone growth and skeletal development.

Protein Structure:

• Length and Composition: PAPPA consists of 1,544 amino acids.
• Domains: It contains a metalloproteinase domain essential for its enzymatic activity, a protease-associated (PA) domain, and multiple hemopexin-like repeats that are involved in substrate recognition and binding.
• Post-Translational Modifications: PAPPA undergoes glycosylation, which is critical for its stability and function. It also requires zinc for its metalloproteinase activity.

Classification and Subtypes:

• Family: PAPPA is a member of the metzincin superfamily, specifically the pappalysin family.
• Isoforms: There are no significant isoforms of PAPPA, but it can exist in different glycosylation states which may affect its activity.

Function and Biological Significance:

• IGFBP Proteolysis: PAPPA is known for its role in cleaving insulin-like growth factor binding proteins (IGFBPs), particularly IGFBP-4 and IGFBP-5. This proteolytic activity releases insulin-like growth factors (IGFs), which are crucial for fetal development and growth by promoting cell proliferation and differentiation.
• Pregnancy: Elevated levels of PAPPA are crucial during pregnancy for normal fetal development. It is involved in modulating IGF bioavailability, thus influencing placental and fetal growth.
• Tissue Remodeling: Beyond pregnancy, PAPPA is involved in tissue remodeling and repair due to its ability to regulate IGF activity in various tissues.

Interactions:

• IGFBPs: PAPPA interacts with and cleaves IGFBPs, regulating the availability of IGFs.
• Stanniocalcin-2 (STC2): STC2 can inhibit PAPPA activity by forming a complex, thus modulating its function in IGF signaling pathways.

Clinical Issues:

• Prenatal Screening: PAPPA is a key component of the first trimester combined screening for Down syndrome and other chromosomal abnormalities. Low levels of PAPPA in maternal serum are associated with an increased risk of chromosomal anomalies such as trisomy 21.
• Cardiovascular Disease: Research has shown that PAPPA levels are elevated in acute coronary syndromes and may serve as a biomarker for unstable atherosclerotic plaques, contributing to cardiovascular risk assessment.
• Cancer: Alterations in PAPPA expression have been observed in various cancers, suggesting a role in tumor progression and metastasis through IGF regulation.
• Preeclampsia: Low PAPPA levels during pregnancy are associated with an increased risk of preeclampsia, a condition characterized by high blood pressure and potential damage to other organ systems, often the liver and kidneys.

Summary:

Pregnancy Associated Plasma Protein-A (PAPPA) is a vital metalloproteinase primarily produced by the placenta, playing a significant role in regulating insulin-like growth factor (IGF) activity by cleaving IGF binding proteins. This regulation is crucial for fetal development and growth. PAPPA's levels are measured in prenatal screening tests to assess the risk of chromosomal abnormalities and other pregnancy-related conditions. Beyond pregnancy, PAPPA has implications in cardiovascular health and cancer, highlighting its broad physiological and pathological significance. Understanding PAPPA's functions and interactions can aid in diagnosing and managing various conditions, particularly those related to pregnancy and cardiovascular diseases.