SMAD2 Gene Summary [Human]
The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
Details
| Type | Protein Coding |
| Official Symbol | SMAD2 |
| Official Name | SMAD family member 2 [Source:HGNC Symbol;Acc:HGNC:6768] |
| Ensembl ID | ENSG00000175387 |
| Bio databases IDs | |
| Aliases | SMAD family member 2 |
| Synonyms | 7120426M23RIK, CHTD8, hMAD-2, hSMAD2, JV18, JV18-1, LDS6, MADH2, MADR2, mMad2, SMAD family member 2 |
| 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 SMAD2 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
- mad homology domain 1
- SSXS motif
- transcription factor binding
- chromatin binding
- identical protein binding
- N-terminal Mad Homology 1 (MH1) domain
- RNA polymerase II transcription factor activity, sequence-specific DNA binding
- tau protein binding
- MH1 domain
- C-terminal Mad Homology 2 (MH2) domain
- phosphatase binding
- ubiquitin protein ligase binding
- RNA polymerase II transcription regulatory region sequence-specific binding transcriptional activator activity
- MH2 domain
- SSMS domain
- MH domain
- nucleic acid binding
- PPXY motif
- linker domain
- protein domain specific binding
- protein binding
- sequence-specific DNA binding
- DNA binding
- phosphorylation site
- Erk1/2 phosphorylation site
- double-stranded DNA binding
- transforming growth factor-beta receptor binding
- transcription factor activity
Pathways
Biological processes and signaling networks where the SMAD2 gene in human plays a role, providing insight into its function and relevance in health or disease.
- Antiproliferative Role of TOB in T Cell Signaling
- Colorectal Cancer Metastasis Signaling
- Factors Promoting Cardiogenesis in Vertebrates
- GADD45 Signaling
- Glucocorticoid Receptor Signaling
- Hepatic Fibrosis / Hepatic Stellate Cell Activation
- HIPPO signaling
- Human Embryonic Stem Cell Pluripotency
- Iron homeostasis signaling pathway
- Molecular Mechanisms of Cancer
- 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
- neoplasia
- metastatic colon cancer
- colorectal cancer
- epithelial cancer
- epithelial neoplasia
- cancer
- non-small cell lung cancer
- lung squamous cell carcinoma
- squamous cell lung cancer
- metastatic breast cancer
role in cell
- expression in
- proliferation
- phosphorylation in
- migration
- apoptosis
- survival
- cell viability
- formation
- quantity
- cell death
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
- cytosol
- caveolar membranes
- nucleoplasm
- nuclear speckles
- chromatin
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human SMAD2 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- cell proliferation
- organ growth
- insulin secretion
- zygotic specification of dorsal/ventral axis
- negative regulation of cell proliferation
- post-embryonic development
- anterior/posterior pattern specification
- transforming growth factor beta receptor signaling pathway
- signal transduction involved in regulation of gene expression
- anatomical structure morphogenesis
- positive regulation of transcription from RNA polymerase II promoter
- embryonic foregut morphogenesis
- nodal signaling pathway
- positive regulation of epithelial to mesenchymal transition
- activin receptor signaling pathway
- endocardial cushion morphogenesis
- paraxial mesoderm morphogenesis
- negative regulation of transcription, DNA-dependent
- cellular response to glucose stimulus
- positive regulation of transcription, DNA-dependent
- in utero embryonic development
- endoderm formation
- odontoblast differentiation
- mesoderm formation
- intracellular signal transduction
- adrenal gland development
- response to cholesterol
- lung development
- pancreas development
- aortic valve morphogenesis
- primary miRNA processing
- transcription, DNA-dependent
- SMAD protein signal transduction
- pulmonary valve morphogenesis
- determination of left/right asymmetry in lateral mesoderm
- embryonic cranial skeleton morphogenesis
- regulation of transcription, DNA-dependent
- pericardium development
- gastrulation
- positive regulation of BMP signaling pathway
- ureteric bud development
- positive regulation of gene expression
- regulation of binding
- cell fate commitment
- cell differentiation
- regulation of transforming growth factor beta receptor signaling pathway
Cellular Component
Where in the cell the gene product is active
- SMAD protein complex
- SMAD2 protein complex
- transcription factor complex
- nucleus
- cytoplasm
- SMAD2-SMAD3 protein complex
- activin responsive factor complex
- cytosol
- macromolecular complex
- chromatin
- nucleoplasm
Molecular Function
What the gene product does at the molecular level
- phosphatase binding
- identical protein binding
- transforming growth factor beta receptor binding
- RNA polymerase II core promoter proximal region sequence-specific DNA binding
- double-stranded DNA binding
- core promoter proximal region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
- chromatin binding
- sequence-specific DNA binding RNA polymerase II transcription factor activity
- DNA binding
- sequence-specific DNA binding transcription factor activity
- protein binding
- ubiquitin protein ligase binding
- SMAD binding
- metal ion binding
- tau protein binding
- R-SMAD binding
- co-SMAD binding
- I-SMAD binding
- type I transforming growth factor beta receptor binding