Concept
SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation. SMAD 4 belongs to the co-SMAD group (common mediator SMAD), the second class of the SMAD family. SMAD4 is the only known co-SMAD in most metazoans. It also belongs to the Darwin family of proteins that modulate members of the TGFβ protein superfamily, a family of proteins that all play a role in the regulation of cellular responses. Mammalian SMAD4 is a homolog of the Drosophila protein "Mothers against decapentaplegic" named Medea. SMAD4 interacts with R-Smads, such as SMAD2, SMAD3, SMAD1, SMAD5 and SMAD8 (also called SMAD9) to form heterotrimeric complexes. Transcriptional coregulators, such as WWTR1 (TAZ) interact with SMADs to promote their function. Once in the nucleus, the complex of SMAD4 and two R-SMADS binds to DNA and regulates the expression of different genes depending on the cellular context. Intracellular reactions involving SMAD4 are triggered by the binding, on the surface of the cells, of growth factors from the TGFβ family. The sequence of intracellular reactions involving SMADS is called the SMAD pathway or the transforming growth factor beta (TGF-β) pathway since the sequence starts with the recognition of TGF-β by cells. In mammals, SMAD4 is coded by a gene located on chromosome 18. In humans, the SMAD4 gene contains 54 829 base pairs and is located from pair n° 51,030,212 to pair 51,085,041 in the region 21.1 of the chromosome 18. SMAD4 is a 552 amino-acid polypeptide with a molecular weight of 60.439 Da. SMAD4 has two functional domains known as MH1 and MH2.
