Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity).
Subcellular locations: Cytoplasm, Nucleus
Cytoplasmic and nuclear in the absence of TGF-beta (By similarity). On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 (By similarity). On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (By similarity). Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity).