SMAD4 is a 552 amino acid protein involved in cell signaling. It belongs to the Darfwin family of proteins which modulate members of the TGF beta protein superfamily. It binds receptor regulated SMADs such as SMAD1 or SMAD2 and forms a complex that binds to DNA and serves as a transcription factor. It is the only known mammalian coSMAD. It is a homolog of the Drosophila protein: "Mothers against decapentaplegic".
The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene, MAD, in the mother, repressed the gene, decapentaplegic, in the embryo.