From Wikipedia, the free encyclopedia
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 .
Activity Regulation Classification Kinetics Types