N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD1, SMAD5 and SMAD9, all closely related receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.
Jiyao W et al.(2023). "The conserved domain database in 2023.",