E3 ubiquitin-protein ligase Arkadia (RNF111)

Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which can be activated downstream of BMP (PubMed:14657019, PubMed:16601693). Acts by mediating ubiquitination and degradation of SMAD inhibitors like SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019, PubMed:16601693).

In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors'in use' are degraded (By similarity). Activates SMAD3/SMAD4- dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (PubMed:17591695).