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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

^ "PAPPA - Pappalysin-1 precursor - Homo sapiens (Human) - PAPPA gene & protein". www.uniprot.org. Retrieved 13 March 2022.
^ ^a ^b 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.
^ ^a ^b "Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1".
^ 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.
^ 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.
^ 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.
^ Alfirevic Z (February 2009). "Prenatal screening for Down's syndrome". BMJ. 338: b140. doi:10.1136/bmj.b140. PMID 19218324. S2CID 40516097.
^ 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.

v t e Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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