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Description

Mothers against decapentaplegic homolog 2 (UniProt: Q15796, also known as MAD homolog 2, Mothers against DPP homolog 2, JV18-1, Mad-related protein 2, hMAD-2, SMAD family member 2, SMAD 2, Smad2, hSMAD2) is encoded by the SMAD2 (also known as MADH2, MADR2) gene (Gene ID: 4087) in human. Smad2 is a receptor-regulated Smad (R-Smad) that serves as an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor beta (TGF beta) and activin type 1 receptor kinases. It is expressed at high levels in skeletal muscle, endothelial cells, heart, and placenta. It contains one Mad homology (MH) 1 domain (aa 10-176), one MH2 domain (aa 274-467) and a PY motif (aa 221-225). Cytoplasmic Smad2 is directly phosphorylated on Ser465/Ser467 by TGF- receptor kinase I. These C-terminal phosphoserines of R-Smads are recognized by the MH2 domain of Smad4 that enables them to form a heterodimeric complex, which translocates to the nucleus where Smad proteins bind to their cognate DNA binding sites with low affinity. This binding is further enhanced in the presence of transcriptional co-activators. Acetylation Lys-19 by coactivators in response to TGF-beta signaling is shown to increase its transcriptional activity. Upon dephosphorylation by phosphatase PPM1A, Smad2 is released from the Smad2/Smad4 complex and is exported out of the nucleus.