IGFBP3
Developmental stage
IGFBP3 levels are higher during extrauterine life and peak during puberty.
Domain
The thyroglobulin type-1 domain mediates interaction with HN.
Function
Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proliferation, differentiation, and apoptosis in a cell-type specific manner (PubMed:10874028, PubMed:19556345). Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R (PubMed:20353938). Inhibits the positive effect of humanin on insulin sensitivity (PubMed:19623253). Promotes testicular germ cell apoptosis (PubMed:19952275). Acts via LRP-1/alpha2M receptor, also known as TGF-beta type V receptor, to mediate cell growth inhibition independent of IGF1 (PubMed:9252371). Mechanistically, induces serine-specific dephosphorylation of IRS1 or IRS2 upon ligation to its receptor, leading to the inhibitory cascade (PubMed:15371331). In the nucleus, interacts with transcription factors such as retinoid X receptor-alpha/RXRA to regulate transcriptional signaling and apoptosis (PubMed:10874028).
Post-translational modifications
Phosphorylated by FAM20C in the extracellular medium. Phosphorylated by CK2; resulting in decreased nuclear localization (PubMed:19556345).
Tissue Specificity
Expressed by most tissues. Present in plasma.
Cellular localization
- Secreted
- Nucleus
Alternative names
IBP3, IGFBP3, Insulin-like growth factor-binding protein 3, IBP-3, IGF-binding protein 3, IGFBP-3