Pappalysin-1

Pappalysin-1, also known as pregnancy-associated plasma protein A, and insulin-like growth factor binding protein-4 protease is a protein encoded by the PAPPA gene in humans.^[1] PAPPA is a secreted protease whose main substrate is insulin-like growth factor binding proteins. Pappalysin-1 is also used in screening tests for Down syndrome.^[2][3]

Function

PAPPA encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). PAPPA's proteolytic function is activated upon collagen binding. It is thought to be involved in local proliferative processes such as wound healing and bone remodeling. Low plasma level of this protein has been suggested as a biochemical marker for pregnancies with aneuploid fetuses (fetuses with an abnormal number of chromosomes).^[3] For example, low PAPPA may be commonly seen in prenatal screening for Down syndrome.^[2] Low levels may alternatively predict issues with the placenta, resulting in adverse complications such as intrauterine growth restriction, preeclampsia, placental abruption, premature birth, or fetal death.

This enzyme catalyses the following chemical reaction:

Cleavage of the Met135-Lys bond in insulin-like growth factor binding protein (IGFBP)-4, and the Ser143-Lys bond in IGFBP-5 This enzyme belongs to the peptidase family M43.

Interactions

Pappalysin-1 has been shown to interact with major basic protein.^[4][5][6]

Studies conducted at the Royal London Hospital in the United Kingdom, have shown that a marker of Down's syndrome may be expressed during the first trimester and second trimester of a pregnancy term. Concentrations of the Pregnancy-Associated Plasma Protein (PAPPA) gene as well as other markers can help screen for Down's syndrome in the beginning stages of a women's gestational period.^[7][8]

References

1. "PAPPA - Pappalysin-1 precursor - Homo sapiens (Human) - PAPPA gene & protein". www.uniprot.org. Retrieved 13 March 2022.
2. Breathnach FM, Malone FD (April 2007). "Screening for aneuploidy in first and second trimesters: is there an optimal paradigm?". Current Opinion in Obstetrics & Gynecology. 19 (2): 176–82. doi:10.1097/GCO.0b013e3280895e00. PMID 17353686. S2CID 25949255.
3. "Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1".
4. Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. (October 2000). "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor". The Journal of Biological Chemistry. 275 (40): 31128–33. doi:10.1074/jbc.M001384200. PMID 10913121.
5. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C (January 2003). "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment". The Journal of Biological Chemistry. 278 (4): 2106–17. doi:10.1074/jbc.M208777200. PMID 12421832.
6. Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L (June 1993). "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein". The Journal of Biological Chemistry. 268 (17): 12243–6. doi:10.1016/S0021-9258(18)31378-4. PMID 7685339.
7. Alfirevic Z (February 2009). "Prenatal screening for Down's syndrome". BMJ. 338: b140. doi:10.1136/bmj.b140. PMID 19218324. S2CID 40516097.
8. Wald N, Stone R, Cuckle HS, Grudzinskas JG, Barkai G, Brambati B, et al. (July 1992). "First trimester concentrations of pregnancy associated plasma protein A and placental protein 14 in Down's syndrome". BMJ. 305 (6844): 28. doi:10.1136/bmj.305.6844.28. PMC 1882510. PMID 1379094.