SMAD2/SMAD3

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. ,

embryonic axis specification , in utero embryonic development , formation of primary germ layer , mesoderm formation ,peptide secretion , generation of a signal involved in cell-cell signaling , regionalization , transcription , regulation of transcription , DNA-dependent , regulation of transcription from RNA polymerase II promoter , RNA processing , protein complex assembly , protein amino acid phosphorylation , phosphorus metabolic process , phosphate metabolic process ,cell surface receptor linked signal transduction , enzyme linked receptor protein signaling pathway , transmembrane receptor protein serine/threonine kinase signaling pathway , transforming growth factor beta receptor signaling pathway , SMAD protein complex assembly , intracellular signaling cascade , cell-cell signaling , zygotic determination of dorsal/ventral axis , gastrulation , pattern specification process , mesoderm development , heart development , negative regulation of cell proliferation , response to carbohydrate stimulus , response to hexose stimulus , response to glucose stimulus , post-embryonic development , embryonic development ending in birth or egg hatching , axis specification ,embryonic pattern specification , negative regulation of biosynthetic process , positive regulation of biosynthetic process , hormone transport , dorsal/ventral axis specification , anterior/posterior pattern formation , dorsal/ventral pattern formation , response to organic substance , positive regulation of macromolecule biosynthetic process , negative regulation of macromolecule biosynthetic process , positive regulation of macromolecule metabolic process , negative regulation of macromolecule metabolic process , posttranscriptional regulation of gene expression , positive regulation of gene expression , negative regulation of gene expression , regulation of epithelial to mesenchymal transition ,positive regulation of epithelial to mesenchymal transition , positive regulation of cell development , regulation of cell morphogenesis involved in differentiation , positive regulation of cell morphogenesis involved in differentiation ,regulation of hormone levels , peptide transport , phosphorylation , posttranscriptional gene silencing , gene silencing ,negative regulation of transcription , regulation of transforming growth factor beta receptor signaling pathway ,regulation of cell morphogenesis , peptide hormone secretion , insulin secretion , respiratory tube development , lung development , pancreas development , gene silencing by RNA , dsRNA fragmentation , primary microRNA processing ,negative regulation of cellular biosynthetic process , positive regulation of cellular biosynthetic process , regulation of gene-specific transcription , secretion by cell , response to lipid , response to monosaccharide stimulus , ncRNA processing , cellular macromolecular complex subunit organization , cellular macromolecular complex assembly ,posttranscriptional gene silencing by RNA , gene silencing by miRNA , gene silencing by miRNA , production of miRNAs ,organ growth , tube development , growth , regulation of gene expression , epigenetic , regulation of cell proliferation ,chordate embryonic development , positive regulation of gene-specific transcription , response to dsRNA , cellular protein complex assembly , macromolecular complex subunit organization , cell fate commitment , regulation of transcription , positive regulation of cell differentiation , negative regulation of transcription , DNA-dependent , positive regulation of transcription , DNA-dependent , negative regulation of nucleobase , nucleoside , nucleotide and nucleic acid metabolic process , positive regulation of nucleobase , nucleoside , nucleotide and nucleic acid metabolic process ,positive regulation of transcription , positive regulation of transcription from RNA polymerase II promoter , hormone secretion , secretion , mesoderm morphogenesis , paraxial mesoderm development , paraxial mesoderm morphogenesis ,embryonic morphogenesis , tissue morphogenesis , positive regulation of developmental process , regulation of binding ,positive regulation of cellular component organization , negative regulation of nitrogen compound metabolic process ,positive regulation of nitrogen compound metabolic process , regulation of RNA metabolic process , negative regulation of RNA metabolic process , positive regulation of RNA metabolic process , palate development , regulation of cell development , respiratory system development , macromolecular complex assembly , protein complex biogenesis ,response to cholesterol ,

Cytoplasm . Nucleus . Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation , migrates to the nucleus when complexed with SMAD4 (PubMed:9865696 , PubMed:21145499) . On dephosphorylation by phosphatase PPM1A , released from the SMAD2/SMAD4 complex , and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101 , PubMed:19289081) . Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity) . .