Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth [ PUBMED:8799132 PUBMED:19218245 ]. The dwarfin family also includes the Drosophila protein MAD that is required … expand

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth [ PUBMED:8799132 PUBMED:19218245 ]. The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signalling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp [ PUBMED:9230443 PUBMED:17507407 ]. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF) [ PUBMED:14631647 ].

This entry represents the SMAD (Mothers against decapentaplegic (MAD) homologue) (also called MH2 for MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five α helices and three loops enclosing a β sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C terminus of MH2 [ PUBMED:8799132 PUBMED:9230443 PUBMED:11532220 ].