C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs
The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD6 and SMAD7 are inhibitory SMADs (I-SMADs) that function as negative regulators of signaling mediated by the TGF-beta superfamily. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling, while SMAD7 enhances muscle differentiation and is often associated with cancer, tissue fibrosis and inflammatory diseases.
Comment:Based on similarity to other members of the family
Comment:Upon phosphorylation of the last two Ser residues of the flexible C-terminal SSXS motif, R-SMADs form extremely stable homotrimers as well as the heteromeric SMAD complexes with SMAD4.
cd10496 is part of a hierarchy of related CD models. Use the graphical representation to navigate this hierarchy. cd10496 is a member of the superfamily cl00056