Phospho-Ser/Thr Binding: MH2 Domain

Domain Binding and Function

The MH2 domain of R-Smads allows the interaction with the Smad binding domain (SBD) of SARA. SARA recruits R-Smads to the type I TGFβ receptor, and this is believed to be stabilized by a charge-mediated interaction between the MH2 domain and the cytoplasmic domain of the type I TGFβ-R. The MH2 of the co-Smad, Smad4, appears to be responsible for homooligomerization of Smad4 trimers into disk-like structures and heterooligomerization between Smad4 trimers and Smad2 trimer disks. Mutations in the Smad4 trimer interface disrupt homo-oligomerization and result in inactivation of Smad4 tumor suppression function observed in pancreatic carcinomas and other cancers.

Structure Reference

1. Wu, G. et al. (2000) Science 287(5450), 92–97.

Examples of Domain Proteins

Binding Examples

MH2 Domain Proteins	Binding Partners
Smad1 (R-Smad)	Type1 TGF-β receptor, BMPR-I group of receptors, ALK1 group of receptors
Smad2 (R-Smad)	SARA
Smad4 (Co-Smad)	Smad4 to form trimers by homo-oligomerization