SMAD (protein)

SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream TGF-β gene transcription.

The SMADs, which form a trimer of two receptor-regulated SMADs and one co-SMAD, act as transcription factors that regulate the expression of certain genes.

Classes
There are three classes of SMAD:
 * 1) The receptor-regulated Smads (R-SMAD) which include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9
 * 2) The common-mediator Smad (co-SMAD) which includes only SMAD4, which interacts with R-SMADs to participate in signaling
 * 3) The antagonistic or inhibitory Smads (I-SMAD) which include SMAD6 and SMAD7, which block the activation of R-SMADs and Co-SMADs.

Nomenclature
The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the Caenorhabditis 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.