Follistatin-like 3 (FSTL-3), also known as Follistatin-related Gene (FLRG) and Follistatin-related protein (FSRP), is a 30-35 kDa secreted glycoprotein. FSTL-3 encodes a novel secreted glycoprotein that is highly homologous to follistatin and binds activins and bone morphogenetic proteins, members of the TGF beta superfamily of growth/differentiation factors. FSTL-3 protein inhibits activin-induced and bone morphogenetic protein-2-induced transcriptional responses in a dose-dependent manner, and its mRNA is abundantly expressed in human placenta, trophoblast, heart, uterus, ovary, testis and adrenal gland. Mature human FSTL-3 consists of an Activin and Myostatin binding N-terminal domain, two Follistatin-like domains, and two Kazal-like domains. BMP-2, -6, and -7 do not compete for Activin A binding, and FSTL-3 binds only weakly to Activin B. Unlike Follistatin, FSTL-3 does not contain a heparin-binding domain and does not interact with heparin sulfate proteoglycans. FSTL-3 has been studied in regulation of energy balance and metabolism, gestational diabetes, preeclampsia, and promotor of tumor cell proliferation.
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