The superfamily of insulin-like growth factor (IGF) binding proteins include the six high-affinity IGF binding proteins (IGFBP) and at least four additional low-affinity binding proteins referred to as IGFBP related proteins (IGFBP-rP). All IGFBP superfamily members are cysteine-rich proteins with conserved cysteine residues, which are clustered in the amino- and carboxy-terminal thirds of the molecule. IGFBPs modulate the biological activities of IGF proteins. Some IGFBPs may also have intrinsic bioactivity that is independent of their ability to bind IGF proteins. Post-translational modifications of IGFBPs, including glycosylation, phosphorylation and proteolysis, have been shown to modify the affinities of the binding proteins to IGF.
Human IGFBP-3 cDNA encodes a 291 amino acid (aa) residue precursor protein with a putative 27 aa residue signal peptide that is processed to generate the 264 aa residue mature protein with three potential N-linked and two potential O-linked glycosylation sites. Human IGFBP-3 is expressed in multiple tissues. The highest expression level is found in the non-paranchymal cells of the liver. Expression levels are also higher during extrauterine life and peak during puberty. Human IGFBP-3 is the major IGF binding protein in plasma where it exists in a ternary complex with IGF-I or IGF-II and the acid-labile subunit (ALS).
