Smad4 is encoded by the Smad4 gene that is located on chromosome 18 in humans. Smad4 is also known as Smad family member 4, Sma- and Mad-related protein 4 or Mothers against decapentaplegic (MAD) homolog 4. Smad4 contains N-terminal MH1 (MAD homology 1) and C-terminal MH2 (MAD homology 2) globular domains that are involved in DNA binding and protein interactions respectively. Binding of the TGF-beta superfamily of ligands that includes Transforming Growth Factor -beta (TGF-beta) and bone morphogenetic protein (BMP) to its cognate receptor allows phosphorylation of Smad 1, 2, 3, 5 and 8 (R-Smad, Receptor Smad). This signals for heterotrimerization with Smad4 (co-Smad, co-mediator Smad) and translocation of the complex to the nucleus. Inhibitory or antagonistic Smad (I-Smad) that includes Smad 6 and 7, interact with activated R-Smads and attenuate the signaling pathway. Smad4 acts as a tumor suppressor protein by transcriptionally regulating its target genes such as Cyclin D1 (downregulation) and collagen (upregulation) that inhibit cell proliferation. Dephosphorylation regulates nuclear export and nucleocytoplasmic dynamics of Smads.
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Protein Aliases: deleted in pancreatic carcinoma locus 4; Deletion target in pancreatic carcinoma 4; Deletion target in pancreatic carcinoma 4 homolog; hSMAD4; MAD (mothers against decapentaplegic Drosophila) homolog 4; MAD homolog 4; Mothers against decapentaplegic homolog 4; mothers against decapentaplegic, Drosophila, homolog of, 4; mothers against DPP homolog 4; SMAD; SMAD 4; SMAD family member 4; SMAD, mothers against DPP homolog 4
Gene Aliases: AW743858; D18Wsu70e; DPC4; JIP; MADH4; MYHRS; SMAD4