Pappalysin-1

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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]

Contents

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]

Related Research Articles

Insulin-like growth factor Proteins similar to insulin that stimulate cell proliferation

The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors, two ligands, a family of seven high-affinity IGF-binding proteins, as well as associated IGFBP degrading enzymes, referred to collectively as proteases.

Pre-eclampsia Hypertension occurring during pregnancy

Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of undesirable outcomes for both the mother and the fetus. If left untreated, it may result in seizures at which point it is known as eclampsia.

alpha-2-Macroglobulin

alpha-2-Macroglobulin (α2M) is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.

Insulin-like growth factor 1 Protein-coding gene in the species Homo sapiens

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.

Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

Gestational hypertension Medical condition

Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hypertension is defined as having a blood pressure greater than 140/90 on two occasions at least 6 hours apart.

Insulin-like growth factor 2 Major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults."[5]

Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults."

Major basic protein

Eosinophil major basic protein, often shortened to major basic protein is encoded in humans by the PRG2 gene.

Insulin-like growth factor-binding protein Transport protein for insulin-like growth factor 1

The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1).

IGFBP3

Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.

IGFBP2

Insulin-like growth factor-binding protein 2 is a protein that in humans is encoded by the IGFBP2 gene.

IGFBP5

Insulin-like growth factor-binding protein 5 is a protein that in humans is encoded by the IGFBP5 gene. An IGFBP5 gene was recently identified as being important for adaptation to varying water salinity in fish.

IGFBP4

Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the IGFBP4 gene.

ADAM12 Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.

IGFBP6

Insulin-like growth factor-binding protein 6 (IGFBP-6) is a protein that in humans is encoded by the IGFBP6 gene.

IGFBP1

Insulin-like growth factor-binding protein 1 (IBP-1) also known as placental protein 12 (PP12) is a protein that in humans is encoded by the IGFBP1 gene.

IGFBP7

Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the IGFBP7 gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulating IGF binding to its receptors. IGFBP7 binds to IGF with high affinity. It also stimulates cell adhesion. The protein is implicated in some cancers.

IGFALS

Insulin-like growth factor binding protein, acid labile subunit, also known as IGFALS, is a protein which in humans is encoded by the IGFALS gene.

Pregnancy zone protein

Pregnancy zone protein (PZP), also known as the pregnancy-associated α2-glycoprotein, is a protein which in humans is encoded by the PZP gene on chromosome 12. PZP is part of the alpha-2 globulin family of proteins. It is often associated with pregnancy, during which it can be the most abundant amongst the plasma proteins. PZP is believed to play a role in immune-regulation during pregnancy, however many aspects of its mechanism, function and structure are yet to be determined. Recent research has largely focused on determining how dysregulated PZP levels can act as a markers of various diseases.

PAPPA2

Pappalysin-2 is a protein that in humans is encoded by the PAPPA2 gene.

References

  1. ↑ "PAPPA - Pappalysin-1 precursor - Homo sapiens (Human) - PAPPA gene & protein". www.uniprot.org. Retrieved 13 March 2022.
  2. 1 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. 1 2 "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.


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