a transcription factor that transduces signals from receptors of transforming growth factor beta (TGF-B) and activin type 1 receptor kinases that regulate cell development and growth. Binds directly to consensus DNA-binding elements in the promoters of target genes. Upon formation of the SMAD3/SMAD4 complex, activates transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. In the mouse, it is required for establishemnt of the mucosal immune response and proper development of skeleton. It can form complexes that include, for example, SMAD4/JUN/FOS, SMAD2/SMAD4, and AIP1, ACVR2A, and ACVR1B. Interacts with DACH1, inhibiting TGF-beta signaling. Interacts (via the MH2 domain) with LEMD3, repressing SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts (via the linker region) with EP300 (C-terminal), promoting SMAD3 acetylation. Interacts with SKI, repressing SMAD3 transcriptional activity. Interacts with PPM1A which dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. Interacts with RANBP3, resulting in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. TGF-beta stimulation enhances interactions with DAB2. Interacts with PPP5C, decreasing SMAD3 phosphorylation and protein levels. Interacts (when phosphorylated) with RNF111, which acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors. Belongs to the dwarfin/SMAD family. Four alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Nuclear receptor co-regulator; Transcription factor