The Smad family of proteins are functioning in the transmission of extracellular signals in the TGF-beta signaling pathway. Binding of a TGF-beta superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression. In mammals, eight Smad proteins have been identified to date. The Smad family of proteins can be divided into three functional groups: the receptor-activated Smads (R-Smads), common mediator Smads (Co-Smads), and the inhibitory Smads (I-Smads). The R-Smads are directly phosphorylated by the activated type I receptors on their C-terminal Ser-Ser-X-Ser (SSXS) motif and include Smad1, Smad2, Smad3, Smad5, and Smad8. Smad2 and Smad3 are phosphorylated in response to TGF-beta and activin, whereas Smad1, Smad5, and Smad8 are phosphorylated in response to BMP (Bone Morphogenetic Protein). This C-terminal phosphorylation allows R-Smad binding to Co-Smad, Smad4, and translocation to the nucleus where they regulate TGF-beta target genes. Smad6 and Smad7 belong to the I-Smad which bind to the type I receptor or Smad4 and block their interaction with R-Smads.
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Protein Aliases: BSP-1; Dwarfin-A; Dwarfin-C; Dwf-A; Dwf-C; hSMAD1; hSmad5; JV4-1; JV5-1; MAD homolog 1; MAD homolog 5; MAD, mothers against decapentaplegic homolog 1; MAD, mothers against decapentaplegic homolog 5; Mad-related protein 1; mMad1; Mothers against decapentaplegic homolog 1; Mothers against decapentaplegic homolog 5; mothers against decapentaplegic, drosophila, homolog of, 5; mothers against DPP homolog 1; mothers against DPP homolog 5; Mothers-against-DPP-related 1; mSmad5; OTTHUMP00000223331; SMA- and MAD-related protein 5; SMAD; SMAD 1; SMAD 5; SMAD family member 1; SMAD family member 5; SMAD, mothers against DPP homolog 1; SMAD, mothers against DPP homolog 5; TGF-beta signaling protein 1; transforming growth factor-beta signaling protein 1; Transforming growth factor-beta-signaling protein 1
Gene Aliases: 1110051M15Rik; AI451355; AI528653; BSP-1; BSP1; Dwf-C; DWFC; JV4-1; JV41; JV5-1; MADH1; MADH5; MADR1; Mlp1; Msmad5; MusMLP; SMAD1; SMAD5
Molecular Function: transcription factor