Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators. SMAD6 is an inhibitory Smad (i-Smad) that negatively regulates signaling downstream of type I transforming growth factor-beta (   , ). Acts as a mediator of TGF-beta and BMP anti-inflammatory activities. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of pro-inflammatory genes . Blocks the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding (, ). Binds to regulatory elements in target promoter regions .
Subcellular locations: Nucleus
Expressed in the brain, heart, ovary, peripheral blood leukocytes, small intestine, spleen, thymus, bone marrow, fetal liver and lymph nodes.