pappalysin-1 (pregnancy-associated plasma protein-A, PAPP-A, insulin-like growth factor-dependent IGF-binding protein 4 protease, IGF-dependent IGFBP-4 protease, IGFBP-4ase, PAPPA)
Jump to navigation
Jump to search
Function
- metalloproteinase
- specifically cleaves IGFBP-4 & IGFBP-5, resulting in release of bound IGF
- cleavage of IGFBP-4 is enhanced by IGF cleavage of IGFBP-5 is inhibited by IGF (slight)
- cleavage of the 135-Met-|-Lys-136 bond in IGFBP4 & 143-Ser-|-Lys-144 bond in IGFBP-5
- inhibited by complexation with the proform of PRG2
- induction by 8-bromoadenosine-3',5'-phosphate
Cofactor: binds 1 Zn+2 per subunit
Structure
- homodimer; disulfide-linked
- in pregnancy serum, predominantly found as a disulfide- linked 2:2 heterotetramer with proform of PRG2
- belongs to the peptidase M43B family.
- contains 5 Sushi domains (CCP/SCR domains)
Compartment
Expression
- expressed in placenta > other tissues
- X cells in septa & anchoring villi
- syncytiotrophoblasts in chorionic villi
- expressed in kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts, osteoblasts
- present in serum & placenta during pregnancy
- levels increase throughout pregnancy