SMAD2: A Key Mediator of TGF-β Signaling
SMAD2 gene, protein, function, mutations, and associated diseases
Gene Information Card
| Symbol | SMAD2 |
|---|---|
| Full Name | SMAD family member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q21.1 |
| NCBI Gene ID | 4087 ncbi.nlm.nih.gov/gene/4087 |
| Ensembl ID | ENSG00000175387 |
| UniProt ID | Q15796 |
| OMIM ID | 601366 |
| HGNC ID | 6768 |
| Aliases | MADH2, MADR2, JV18-1, hSMAD2 |
Description
SMAD2 (SMAD family member 2) is a protein-coding gene that encodes a key intracellular mediator of the transforming growth factor-beta (TGF-β) signaling pathway. Upon TGF-β receptor activation, SMAD2 is phosphorylated, forms a complex with SMAD4, and translocates to the nucleus to regulate transcription of target genes involved in cell growth, differentiation, apoptosis, and immune regulation. SMAD2 is a tumor suppressor gene frequently altered in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemorrhagic Telangiectasia (HHT) | Loss-of-function mutations in SMAD2 impair TGF-β signaling in endothelial cells, leading to vascular malformations. | ClinVar, OMIM |
| Colorectal Cancer | SMAD2 mutations or deletions disrupt TGF-β-mediated growth inhibition, promoting tumor progression. | COSMIC, NCBI |
| Pancreatic Cancer | SMAD2 inactivation via mutation or loss of heterozygosity contributes to TGF-β resistance and metastasis. | COSMIC, PubMed |
| Lung Cancer | SMAD2 alterations (mutations, reduced expression) are associated with poor prognosis and epithelial-mesenchymal transition. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.0 | High |
| Spleen | 22.5 | High |
| Lung | 18.3 | Medium |
| Liver | 15.1 | Medium |
| Brain | 12.4 | Medium |
| Heart | 10.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 25.0 | Embryonic kidney cells; high endogenous expression |
| HeLa | 20.5 | Cervical cancer cells; moderate expression |
| A549 | 18.0 | Lung adenocarcinoma cells; moderate expression |
| MCF7 | 15.2 | Breast cancer cells; moderate expression |
| HepG2 | 12.8 | Hepatocellular carcinoma cells; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.860C>T (p.Pro287Leu) | Missense | <1% | Impaired phosphorylation and nuclear translocation; loss of function |
| c.1081_1082del (p.Leu361fs) | Frameshift | <1% | Truncated protein; loss of function |
| c.1132A>G (p.Lys378Glu) | Missense | <1% | Reduced DNA binding; dominant-negative effect |
| c.1244G>A (p.Arg415Gln) | Missense | <1% | Impaired SMAD4 interaction; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SMAD2 mutations in cancer are loss-of-function, disrupting TGF-β tumor suppressor signaling.
Gain of Function (GOF)
Gain-of-function mutations are rare; some missense variants may enhance transcriptional activity in specific contexts.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Lys378Glu) produce proteins that interfere with wild-type SMAD2 and SMAD4 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• Signaling pathways regulating pluripotency of stem cells (KEGG hsa04550)
• Hippo signaling pathway (KEGG hsa04390)
• Colorectal cancer (KEGG hsa05210)
• Pancreatic cancer (KEGG hsa05212)
Protein Summary
SMAD2 is a 467-amino acid protein (52 kDa) containing an N-terminal MH1 domain (DNA binding), a linker region, and a C-terminal MH2 domain (protein interaction and phosphorylation). It is phosphorylated at Ser465/467 by TGF-β receptor type I. SMAD2 forms heteromeric complexes with SMAD4 and regulates transcription of genes such as SERPINE1, CDKN1A, and MYC. The protein is ubiquitinated and degraded by the proteasome in the absence of TGF-β signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMAD2 Knockout HEK293 Cell Line | EDJ-KQ930 | Human | 4087 | Details Get a Quote |
| SMAD2 Knockout HeLa Cell Line | EDJ-KQ18327 | Human | 4087 | Details Get a Quote |
| SMAD2 Knockout A-549 Cell Line | EDJ-KQ19908 | Human | 4087 | Details Get a Quote |
| SMAD2 Knockout HCT 116 Cell Line | EDJ-KQ19909 | Human | 4087 | Details Get a Quote |
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