Description
Product Characteristics:
Smad2 is a 58 kDa member of a family of proteins involved in cell proliferation, differentiation and development. The Smad family is divided into three subclasses: receptor-regulated Smad's, activin/TGF alpha receptor-regulated (Smad2 and 3) or BMP receptor regulated (Smad1, 5, and 8), the common partner, (Smad4) that functions via its interaction to the various Smad's, and the inhibitory Smad's, (Smad6 and Smad7). Smad2 consists of two highly conserved domains, the N terminal Mad homology (MH1) and the C-terminal Mad homology 2 (MH2) domains. The MH1 domain binds DNA and regulates nuclear import and transcription while the MH2 domain conserved among all the Smad's regulates Smad2 oligomerization and binding to cytoplasmic adaptors and transcription factors. Activated Smad2 associates with Smad4 and translocates as a complex into the nucleus, allowing its binding to DNA and transcription factors. This translocation of Smad2 (as well as Smad3) into the nucleus is a central event in TGF beta signaling. Phosphorylation of threonine 8 in the calmodulin binding region of the MH1 domain by extracellular signal regulated kinase 1(ERK 1) enhances Smad2 transcriptional activity, which is negatively regulated by calmodulin. The regulation of Smad2 phosphorylation on threonine 8 by ERK 1 and calmodulin is critical for Smad2 mediated signaling.
Subcellular location: Cytoplasm, Nucleus
Synonyms: Smad2p-Ser465/467, p-Smad2Ser465/467, Smad2p-S465/467, hMAD 2, hSMAD2, JV18 1, JV18, JV181, MAD, MAD Related Protein 2, MADH2, MADR2, MGC22139, MGC34440, Mothers Against Decapentaplegic Homolog 2, mothers against DPP homolog 2, SMAD 2, SMAD, SMAD2, SMAD2_HUMAN.
Target Information: The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]