Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth [ PUBMED:8799132 ]. 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 … expand

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth [ PUBMED:8799132 ]. 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 ]. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF).

This entry represents the MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue β hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [ PUBMED:11532220 PUBMED:9230443 PUBMED:8799132 ].