BAMBI (BMP and activin membrane-bound inhibitor) is a transmembrane protein closely related to TGF-beta family receptors type I, but without serine/threonine kinase activity. In Xenopus, BAMBI expression is regulated by BMP4. BAMBI interferes with BMP, activin and TGF-beta receptor complex signaling. BAMBI binds various TGF-beta type I receptors, showing the highest affinity for TGFBR1. BAMBI can also bind TGFBR2 and activin receptor type II (Onichtchouk et al. 1999). BAMBI binds SMAD7, and this interaction involves MH1 and MH2 domains of SMAD7 and the intracellular domain of BAMBI. BAMBI and SMAD7 cooperate in the repression of TGF-beta receptor complex signaling, but BAMBI-mediated recruitment of SMAD7 to activated TGF-beta receptor complex, as BAMBI preferentially binds activated TGFBR1, does not lead to TGFBR1 degradation (Yan et al. 2009). BAMBI may downregulate TGF-beta receptor complex signaling by replacing one TGFBR1 molecule in the TGF-beta receptor heterotetramer (Onichtchouk et al. 1999). Alternatively, BAMBI-mediated recruitment of SMAD7 may compete with binding of SMAD2 and SMAD3 (R-SMADs) to the activated TGF-beta receptor complex, thus interfering with the activation of R-SMADs (Yan et al. 2009).