The MH2 domain is found in the SMAD (small mothers against decapentaplegic) family of proteins and is responsible for type I receptor interactions, 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. The MH2 domain is multifunctional and provides SMADs with their specificity and selectivity, as well as transcriptional activity. Several transcriptional co-activators and repressors have also been reported to regulate SMAD signaling by interacting with the MH2 domain. Mutations in the MH2 domains of SMAD2 and especially SMAD4 have been detected in colorectal and other human cancers.
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 heteromeric SMAD complexes with SMAD4.
Structure:3GMJ: Drosophila melanogaster Mad MH2 domain homotrimer; contacts at 4.0A
Jiyao W et al.(2023). "The conserved domain database in 2023.",