SMAD3 a transcription factor that transduces signals from receptors of transforming growth factor beta (TGF-B) and activin type 1 receptor kinases that regulate cell development and growth. Binds directly to consensus DNA-binding elements in the promoters of target genes. Upon formation of the SMAD3/SMAD4 complex, activates transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. In the mouse, it is required for establishemnt of the mucosal immune response and proper development of skeleton. It can form complexes that include, for example, SMAD4/JUN/FOS, SMAD2/SMAD4, and AIP1, ACVR2A, and ACVR1B. Interacts with DACH1, inhibiting TGF-beta signaling. Interacts (via the MH2 domain) with LEMD3, repressing SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts (via the linker region) with EP300 (C-terminal), promoting SMAD3 acetylation. Interacts with SKI, repressing SMAD3 transcriptional activity. Interacts with PPM1A which dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. Interacts with RANBP3, resulting in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. TGF-beta stimulation enhances interactions with DAB2. Interacts with PPP5C, decreasing SMAD3 phosphorylation and protein levels. Interacts (when phosphorylated) with RNF111, which acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors. Belongs to the dwarfin/SMAD family. Four alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Nuclear receptor co-regulator; Transcription factor
Chromosomal Location of rat Ortholog: 8q24
Cellular Component:  chromatin; cytoplasm; cytosol; heteromeric SMAD protein complex; nuclear inner membrane; nucleoplasm; nucleus; plasma membrane; protein-containing complex; receptor complex; SMAD protein complex; transcription regulator complex
Molecular Function:  beta-catenin binding; bHLH transcription factor binding; chromatin binding; chromatin DNA binding; cis-regulatory region sequence-specific DNA binding; co-SMAD binding; collagen binding; DEAD/H-box RNA helicase binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; DNA-binding transcription factor activity, RNA polymerase II-specific; DNA-binding transcription factor binding; DNA-binding transcription repressor activity; double-stranded DNA binding; enzyme binding; I-SMAD binding; identical protein binding; metal ion binding; nuclear glucocorticoid receptor binding; nuclear mineralocorticoid receptor binding; nuclear receptor binding; phosphatase binding; promoter-specific chromatin binding; protein binding; protein homodimerization activity; protein kinase binding; R-SMAD binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding; RNA polymerase II-specific DNA-binding transcription factor binding; sequence-specific DNA binding; SMAD binding; sterol response element binding; transcription cis-regulatory region binding; transcription coactivator binding; transforming growth factor beta receptor binding; ubiquitin binding; ubiquitin protein ligase binding; zinc ion binding
Biological Process:  activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; activin receptor signaling pathway; adrenal gland development; anatomical structure morphogenesis; BMP signaling pathway; cell differentiation; cell-cell junction organization; cellular response to transforming growth factor beta stimulus; cellular response to virus; developmental growth; embryonic cranial skeleton morphogenesis; embryonic foregut morphogenesis; embryonic pattern specification; endoderm development; extrinsic apoptotic signaling pathway; gastrulation; heart looping; immune response; immune system development; in utero embryonic development; JNK cascade; lens fiber cell differentiation; liver development; MAPK cascade; mesoderm formation; negative regulation of apoptotic process; negative regulation of cardiac muscle hypertrophy in response to stress; negative regulation of cell growth; negative regulation of cell population proliferation; negative regulation of cytosolic calcium ion concentration; negative regulation of fat cell differentiation; negative regulation of gene expression; negative regulation of inflammatory response; negative regulation of lung blood pressure; negative regulation of osteoblast differentiation; negative regulation of osteoblast proliferation; negative regulation of protein catabolic process; negative regulation of transcription by RNA polymerase II; negative regulation of wound healing; nodal signaling pathway; osteoblast development; osteoblast differentiation; paraxial mesoderm morphogenesis; pericardium development; positive regulation of alkaline phosphatase activity; positive regulation of bone mineralization; positive regulation of canonical Wnt signaling pathway; positive regulation of cell migration; positive regulation of chondrocyte differentiation; positive regulation of DNA-templated transcription; positive regulation of epithelial to mesenchymal transition; positive regulation of extracellular matrix assembly; positive regulation of focal adhesion assembly; positive regulation of gene expression; positive regulation of interleukin-1 beta production; positive regulation of miRNA transcription; positive regulation of nitric oxide biosynthetic process; positive regulation of positive chemotaxis; positive regulation of stress fiber assembly; positive regulation of transcription by RNA polymerase II; positive regulation of transforming growth factor beta3 production; protein stabilization; regulation of binding; regulation of DNA-templated transcription; regulation of epithelial cell proliferation; regulation of immune response; regulation of striated muscle tissue development; regulation of transcription by RNA polymerase II; regulation of transforming growth factor beta receptor signaling pathway; regulation of transforming growth factor beta2 production; response to hypoxia; signal transduction involved in regulation of gene expression; skeletal system development; SMAD protein complex assembly; SMAD protein signal transduction; somitogenesis; T cell activation; thyroid gland development; transdifferentiation; transforming growth factor beta receptor signaling pathway; ureteric bud development
Reference #:  P84025 (UniProtKB)
Alt. Names/Synonyms: MAD (mothers against decapentaplegic, Drosophila) homolog 3; MAD homolog 3; Mad3; Madh3; Mothers against decapentaplegic homolog 3; Mothers against DPP homolog 3; SMAD 3; SMAD family member 3; Smad3
Gene Symbols: Smad3
Molecular weight: 48,081 Da
Basal Isoelectric point: 6.73  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  ESC Pluripotency and Differentiation  |  G1/S Checkpoint  |  TGF-ß Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene  |  NURSA