SMAD3 Human

The name “Mothers Against Decapentaplegic” originates from research conducted on the fruit fly, Drosophila melanogaster. In Drosophila, a mutation in the gene of the mother repressed the gene decapentaplegic in the embryo, leading to the humorous naming convention . SMAD3 is one of several human homologues of this gene, and it was discovered as part of the broader SMAD family of proteins.

The human SMAD3 gene is located on chromosome 15 at the cytogenetic band 15q22.33. It consists of 9 exons spanning 129,339 base pairs . The SMAD3 protein is a polypeptide with a molecular weight of approximately 48,080 Da .

SMAD3 acts as a mediator of signals initiated by the TGF-β superfamily of cytokines. These cytokines include nodal, activin, and myostatin, among others. The receptors for TGF-β are membrane serine/threonine kinases that preferentially phosphorylate and activate SMAD2 and SMAD3 . Once phosphorylated, SMAD3 forms a heterodimeric complex with SMAD4, which is essential for the transcriptional regulation of many target genes .

The complex of two SMAD3 (or two SMAD2) and one SMAD4 binds directly to DNA through interactions of the MH1 domain. These complexes are recruited to sites throughout the genome by cell lineage-defining transcription factors (LDTFs), which determine the context-dependent nature of TGF-β action .

SMAD3 has been implicated in various diseases, particularly in cancer development. Its role in the TGF-β signaling pathway makes it a critical player in tumor growth and progression . Additionally, SMAD3-knockout mice have been used as models for studying human aneurysms-osteoarthritis syndrome (AOS), also known as Loeys-Dietz Syndrome (type 3) .

The study of SMAD3 and its recombinant forms continues to be a significant area of research. Understanding its function and regulation can provide insights into therapeutic targets for diseases related to the TGF-β signaling pathway.