Rabbit Anti-Human SMAD4 monoclonal antibody for FC, ICC, IF, WB. 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.