Disease:Defects in SMAD2 are found in sporadic cases of colorectal carcinoma. ,Function:Transcriptional modulator activated by TGF-beta and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD) . May act as a tumor suppressor in colorectal carcinoma. ,PTM:Acetylated on Lys-19 by coactivators in response to TGF-beta signaling , which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. ,PTM:In response to TGF-beta , ubiquitinated by NEDD4L; which promotes its degradation. ,PTM:Phosphorylated on one or several of Thr-220 , Ser-245 , Ser-250 , and Ser-255. In response to TGF-beta , phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. Able to interact with SMURF2 when phosphorylated on Ser-465/467 , recruiting other proteins , such as SNON , for degradation. In response to decorin , the naturally occurring inhibitor of TGF-beta signaling , phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability , and is blocked by calmodulin. ,similarity:Belongs to the dwarfin/SMAD family. ,similarity:Contains 1 MH1 (MAD homology 1) domain. ,similarity:Contains 1 MH2 (MAD homology 2) domain. ,subcellular location:Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4. ,subunit:Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts with SARA (SMAD anchor for receptor activation) ; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1 , homeobox protein TGIF , PEBP2-alpha subunit , CREB-binding protein (CBP) , EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta (By similarity) . Interacts with LBXCOR1 and CORL2. ,tissue specificity:Expressed at high levels in skeletal muscle , heart and placenta. ,
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