SMAD2, also named as MADH2 and MADR2, belongs to the dwarfin/SMAD family, contains 1 MH1 (MAD homology 1) domain and 1 MH2 (MAD homology 2) domain. SMAD2 is a receptor-regulated SMAD(R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. This protein may act as a tumor suppressor in colorectal carcinoma. It is phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, It is phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases, and then able to interact with SMURF2, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, it is phosphorylated on Ser-240 by CaMK2. It is phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. In response to TGF-beta, it is ubiquitinated by NEDD4L, which promotes its degradation. In response to TGF-beta signaling, it is acetylated on Lys-19 by coactivators, which increases transcriptional activity.