Follistatin-Related Gene Protein (FLRG)

Follistatin-Related Gene Protein (FLRG), also known as follistatin-like 3 (FSTL3) is a glycoprotein belonging to the follistatin-module protein family. Mouse FLRG cDNA encodes a 256 amino acid (aa) residue protein with a putative 23 aa signal peptide, an N-terminal domain, two cysteine rich follistatin-like domains (FS) and a C-terminal acidic domain. Compared to follistatin, FLRG lacks the third FS domain found in follistatin. In addition, FLRG also lacks the heparin binding domain found within the first aminoterminal FS domain of follistatin. Mouse and human FLRG share approximately 83% aa sequence homology. Like follistatin, FLRG has been shown to bind and inhibit the activities of TGFβ family ligands including activin, BMP2, 6, 7, and GDF8/myostatin. While both FLRG and follistatin are located in a wide and overlapping range of adult and fetal tissue, their sites of peak expression differ: FLRG most highly in heart, lung, kidney, placenta and testis, while follistatin is highest in ovary and pituitary. The expression of FLRG is upregulated by TGFβ and activin signaling through Smad proteins. Although FLRG is a secreted protein in many cell types, it has also been localized to the nuclear compartment in HeLa, 293, and CHO cells.