SMAD6

Acts as an inhibitory regulator of signaling mediated by the TGF-beta superfamily, with strong selectivity toward BMP-dependent pathways. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear translocation 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. Associates with regulatory elements in target promoter regions. Functions as an adapter protein that recruits ubiquitin ligases, including SMURF1 and, in some contexts, SMURF2, promoting proteasomal degradation of signaling components and transcription factors such as RUNX2, TBX6, BMPR1A and MYD88..

Function from UniProtKB (O43541), read 2026-09-23. CC BY 4.0.