SMAD2
GeneName
SMAD2
Summary
SMAD2, also known as Smad 2 or SMAD family member 2, is a 52 kDa intracellular protein that plays a pivotal role in the transforming growth factor-beta (TGF-β) signalling pathway. It is primarily expressed in the nucleus and cytoplasm, where it forms complexes with other SMAD proteins, including R-SMADs and co-SMADs, to regulate gene expression. SMAD2 is involved in various biological processes such as cell differentiation, embryonic development, and morphogenesis, particularly in response to TGF-β and activin receptor signalling. It functions as a transcription factor by binding to specific DNA sequences in the regulatory regions of target genes, thereby influencing their transcriptional activity.
Importance
SMAD2 is relevant to: - Developmental biology, particularly in processes like gastrulation and organogenesis, where it regulates cell fate and differentiation. - Cancer research, as alterations in TGF-β signalling and SMAD2 function can contribute to tumour progression and metastasis. - Fibrosis and tissue repair, due to its role in mediating the effects of TGF-β on extracellular matrix production. - Understanding congenital disorders linked to defects in TGF-β signalling pathways, highlighting its significance in developmental anomalies.
Top Products
For researchers investigating SMAD2, we highly recommend the top-selling recombinant monoclonal antibody, Anti-Smad2 antibody [EP784Y] (ab40855). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). With 145 citations, it is well-regarded in the research community, making it an excellent choice for those seeking robust and consistent results in their studies of SMAD2. The Recombinant Human Smad2 protein ELISA Kit (ab85329), supported by 1 citation, is an excellent option for researchers looking to accurately measure Smad2 levels in their experiments.
Abcam Product Citation Summary
The data indicates that SMAD2 is being studied across various species, including bovine, mouse, rat, and human, primarily using Western blotting as the application of choice. The studies focus on diverse biological contexts such as TGF-β signalling, cancer, and drug resistance, highlighting the importance of SMAD2 in cellular signalling pathways and its potential implications in disease mechanisms.
Abcam Product Citation Table
Function
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumor suppressor in colorectal carcinoma (PubMed:8752209).
Involvement in disease
Congenital heart defects, multiple types, 8, with or without heterotaxy
CHTD8
An autosomal dominant disorder characterized by congenital developmental abnormalities involving structures of the heart. Common CHTD8 features include double-outlet right ventricle, unbalanced complete atrioventricular canal, and valvular anomalies. Vascular anomalies include dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to left atrium defect. Patients may also exhibit laterality defects, including dextrocardia, atrial isomerism, dextrogastria, left-sided gallbladder, and intestinal malrotation.
None
The disease is caused by variants affecting the gene represented in this entry.
Loeys-Dietz syndrome 6
LDS6
A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Most LDS6 patients have thoracic aortic aneurysm involving the ascending aorta and/or aortic root, but cerebral and iliac arteries can be affected, and abdominal aortic aneurysm has been observed. Arterial tortuosity involving cerebral vessels, the aorta, and/or iliac arteries has also been reported. LDS6 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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. TGF-beta-induced Ser-465/467 phosphorylation declines progressively in a KMT5A-dependent manner. 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. Phosphorylated by PDPK1.
In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding (By similarity). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD2 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD2 and regulating its turnover (By similarity).
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. Acetylation in the nucleus by EP300 is enhanced by TGF-beta.
Sequence Similarities
Belongs to the dwarfin/SMAD family.
Tissue Specificity
Expressed at high levels in skeletal muscle, endothelial cells, heart and placenta.
Cellular localization
- Cytoplasm
- Nucleus
- Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 (PubMed:21145499, PubMed:9865696). 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).
Alternative names
MADH2, MADR2, SMAD2, SMAD family member 2, SMAD 2, hSMAD2, JV18-1, Mad-related protein 2, Mothers against decapentaplegic homolog 2, hMAD-2, MAD homolog 2, Mothers against DPP homolog 2
Database links
swissprot:Q15796 omim:603109 omim:601366 swissprot:P84022 entrezGene:4087 entrezGene:4088
Other research areas
- Immuno-oncology
- Oncology