SMAD3 Gene Summary [Human]
The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]
Details
| Type | Protein Coding |
| Official Symbol | SMAD3 |
| Official Name | SMAD family member 3 [Source:HGNC Symbol;Acc:HGNC:6769] |
| Ensembl ID | ENSG00000166949 |
| Bio databases IDs | |
| Aliases | SMAD family member 3 |
| Synonyms | DKFZP586N0721, hMAD-3, hSMAD3, HSPC193, HsT17436, JV15-2, LDS1C, LDS3, mad3, MADH3, SMAD family member 3 |
| Species | Human, Homo sapiens |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in human SMAD3 often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- SMAD binding
- transcription regulator
- phosphoacceptor site
- mad homology domain 1
- SSXS motif
- transcription factor binding
- chromatin binding
- identical protein binding
- proline rich domain
- N-terminal Mad Homology 1 (MH1) domain
- ALK5 phosphorylation site
- RNA polymerase II transcription factor activity, sequence-specific DNA binding
- zinc ion binding
- MH1 domain
- serine phosphorylation site
- C-terminal Mad Homology 2 (MH2) domain
- MAP kinase site
- phosphatase binding
- ubiquitin protein ligase binding
- RNA polymerase II transcription regulatory region sequence-specific binding transcriptional activator activity
- activation domain
- ligand-dependent nuclear receptor interactor
- MH2 domain
- protein kinase binding
- DNA binding domain
- MH domain
- nucleic acid binding
- beta-catenin binding
- enzyme binding
- linker domain
- ubiquitin binding
- protein binding
- sequence-specific DNA binding
- DNA binding
- phosphorylation site
- double-stranded DNA binding
- DEAD/H-box RNA helicase binding
- transforming growth factor-beta receptor binding
- collagen binding
- protein homodimerization
- CAD domain
- transcription factor activity
Pathways
Biological processes and signaling networks where the SMAD3 gene in human plays a role, providing insight into its function and relevance in health or disease.
- Adipogenesis pathway
- Androgen Signaling
- Antiproliferative Role of TOB in T Cell Signaling
- Apelin Endothelial Signaling Pathway
- Chronic Myeloid Leukemia Signaling
- Colorectal Cancer Metastasis Signaling
- GADD45 Signaling
- Glucocorticoid Receptor Signaling
- Hepatic Fibrosis / Hepatic Stellate Cell Activation
- HER-2 Signaling in Breast Cancer
- HIPPO signaling
- Human Embryonic Stem Cell Pluripotency
- Iron homeostasis signaling pathway
- Osteoarthritis Pathway
- Pancreatic Adenocarcinoma Signaling
- PPARα/RXRα Activation
- Regulation of IL-2 Expression in Activated and Anergic T Lymphocytes
- Regulation of the Epithelial-Mesenchymal Transition Pathway
- SPINK1 Pancreatic Cancer Pathway
- TGF-β Signaling
- Transcriptional Regulatory Network in Embryonic Stem Cells
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- epithelial neoplasia
- benign neoplasia
- epithelial cancer
- cancer
- metastatic breast cancer
- neoplasia
- chronic lymphocytic leukemia
- bleeding
- metastatic colon cancer
- osteoarthritis
regulated by
- silibinin
- dexamethasone
- genistein
- hesperetin
- curcumin
- folic acid
- naringenin
- cyclosporin A
- doxorubicin
- hydrogen peroxide
role in cell
- adhesion
- cell death
- apoptosis
- cell viability
- expression in
- survival
- growth
- quantity
- binding in
- transcription in
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Nucleus
- nuclear fraction
- intracellular membrane-bounded organelle
- Cytoplasm
- perinuclear region
- Plasma Membrane
- basal bodies
- cytosol
- outer leaflet
- inner nuclear membrane
- nucleoplasm
- nuclear envelope
- nuclear speckles
- chromatin
- cytoplasmic fraction
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human SMAD3 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- endoderm development
- transforming growth factor beta receptor signaling pathway
- signal transduction involved in regulation of gene expression
- negative regulation of protein catabolic process
- JNK cascade
- positive regulation of sequence-specific DNA binding transcription factor activity
- immune system development
- activin receptor signaling pathway
- wound healing
- immune response
- response to hypoxia
- negative regulation of cell growth
- cellular response to glucose stimulus
- in utero embryonic development
- positive regulation of transcription, DNA-dependent
- transdifferentiation
- heart looping
- mesoderm formation
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- regulation of epithelial cell proliferation
- positive regulation of bone mineralization
- negative regulation of wound healing
- positive regulation of protein import into nucleus
- embryonic pattern specification
- negative regulation of inflammatory response
- SMAD protein signal transduction
- positive regulation of positive chemotaxis
- positive regulation of canonical Wnt receptor signaling pathway
- pericardium development
- cell-cell junction organization
- cellular response to transforming growth factor beta stimulus
- negative regulation of gene expression
- positive regulation of focal adhesion assembly
- somitogenesis
- positive regulation of stress fiber assembly
- positive regulation of gene expression
- positive regulation of transforming growth factor beta3 production
- regulation of transforming growth factor beta receptor signaling pathway
- regulation of striated muscle tissue development
- negative regulation of osteoblast proliferation
- positive regulation of cell migration
- cell proliferation
- positive regulation of nitric oxide biosynthetic process
- negative regulation of cell proliferation
- T cell activation
- extrinsic apoptotic signaling pathway
- anatomical structure morphogenesis
- regulation of transforming growth factor beta2 production
- positive regulation of transcription from RNA polymerase II promoter
- embryonic foregut morphogenesis
- nodal signaling pathway
- negative regulation of osteoblast differentiation
- positive regulation of epithelial to mesenchymal transition
- negative regulation of transcription from RNA polymerase II promoter
- paraxial mesoderm morphogenesis
- liver development
- lens fiber cell differentiation
- adrenal gland development
- regulation of immune response
- primary miRNA processing
- negative regulation of fat cell differentiation
- embryonic cranial skeleton morphogenesis
- regulation of transcription, DNA-dependent
- reduction of cytosolic calcium ion concentration
- developmental growth
- osteoblast development
- regulation of transcription from RNA polymerase II promoter
- thyroid gland development
- ureteric bud development
- negative regulation of apoptotic process
- cell differentiation
- positive regulation of chondrocyte differentiation
- protein stabilization
- positive regulation of interleukin-1 beta production
Cellular Component
Where in the cell the gene product is active
- SMAD protein complex
- nucleus
- transcription factor complex
- nuclear inner membrane
- cytoplasm
- SMAD2-SMAD3 protein complex
- cytosol
- receptor complex
- chromatin
- plasma membrane
- nucleoplasm
Molecular Function
What the gene product does at the molecular level
- ligand-dependent nuclear receptor binding
- RNA polymerase II core promoter proximal region sequence-specific DNA binding
- transcription regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
- bHLH transcription factor binding
- transcription coactivator binding
- sequence-specific DNA binding transcription factor activity
- ubiquitin binding
- glucocorticoid receptor binding
- phosphatase binding
- chromatin DNA binding
- protein kinase binding
- identical protein binding
- zinc ion binding
- protein homodimerization activity
- transforming growth factor beta receptor binding
- core promoter proximal region sequence-specific DNA binding
- sequence-specific DNA binding bacterial-type RNA polymerase transcription factor activity involved in negative regulation of transcription
- beta-catenin binding
- sequence-specific DNA binding RNA polymerase II transcription factor activity
- transcription corepressor binding
- DNA binding
- protein binding
- ubiquitin protein ligase binding
- collagen binding
- DEAD/H-box RNA helicase binding
- R-SMAD binding
- co-SMAD binding
- I-SMAD binding
- sterol response element binding
- mineralocorticoid receptor binding