Reaction: Cleavage of the Met135Lys bond in insulin-like growth factor binding protein (IGFBP)-4, and the Ser143Lys bond in IGFBP-5
Other name(s): insulin-like growth factor binding protein-4 protease; pregnancy-associated plasma protein-A
Comments: A 400-kDa disulfide-linked dimer. Circulates in human pregnancy mainly as a complex with the proform of eosinophil major basic protein, which acts as an inhibitor of the peptidase. The rate of hydrolysis of IGFBP-4 is increased about 20-fold by the presence of insulin-like growth factor (IGF), whereas that of IGFBP-5 is decreased about two-fold. In peptidase family M43.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
1. Lawrence, J.B., Oxvig, C., Overgaard, M.T., Sottrup-Jensen, L., Gleich, G.J., Hays L.G., Yates, J.R. 3rd, and Conover, C.A. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc. Natl. Acad. Sci. USA 96 (1999) 3149-3153. [PMID: 10077652]
2. Chen, B.K., Overgaard, M.T., Bale, L.K., Resch, Z.T., Christiansen, M., Oxvig, C. and Conover, C.A. Molecular regulation of the IGF-binding protein-4 protease system in human fibroblasts: identification of a novel inducible inhibitor. Endocrinology 143 (2002) 1199-1205. [PMID: 11897673]