SMAD4 is a member of the Mothers Against Dpp (MAD)-related family of proteins. SMAD4 is functionally distinct among the SMAD family, and is required for the assembly and transcriptional activation of diverse, SMAD-DNA complexes. SMAD4 appears to be not regulated by phosphorylation, but acts as a common mediator of TGF-β, activin, and bone morphogenetic protein signaling responses. SMAD4 is frequently inactivated in pancreatic, biliary and colorectal tumors.
Product Information
Format
Unpurified
Control
SHSY5Y cell lysate
Presentation
Rabbit Monoclonal in buffer containing 50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl containing 40% Glycerol, 0.01% sodium azide and 0.05% BSA.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target. Detect SMAD4 (C-term) using this Anti-SMAD4 (C-term) Antibody, clone EP618Y, Rabbit validated for use in WB, IH(P), IC, FC & IP.
Key Applications
Immunoprecipitation
Western Blotting
Immunohistochemistry (Paraffin)
Immunocytochemistry
Flow Cytometry
Application Notes
Immunohistochemistry Analysis (paraffin): A 1:100-250 dilution from a previous lot detected SMAD4 in human lung carcinoma tissue.
Immunocytochemistry Analysis: A 1:100-250 dilution from a previous lot detected SMAD4 in HeLa cells.
Flow Cytometry: A 1:20 dilution from a previous lot was used in FC.
Immunoprecipitation: A 1:30 dilution from a previous lot was used in IP.
Biological Information
Immunogen
Synthetic peptide corresponding to residues in the C-terminus of human SMAD4.
FUNCTION:Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. May act as a tumor suppressor. SUBUNIT STRUCTURE:May form trimers with receptor-regulated SMAD (R-SMAD). Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. SUBCELLULAR LOCATION:Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD. PTM:Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. INVOLVEMENT IN DISEASE:Defects in SMAD4 are a cause of pancreatic carcinoma [MIM:260350].
Defects in SMAD4 are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.
Defects in SMAD4 are a cause of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050]. JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic aetiology of this association is unknown.
Defects in SMAD4 may be a cause of colorectal cancer (CRC) [MIM:114500]. SEQUENCE SIMILARITIES:Belongs to the dwarfin/SMAD family.
Contains 1 MH1 (MAD homology 1) domain.
Contains 1 MH2 (MAD homology 2) domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blot on SHSY5Y cell lysates.
Western Blot Analysis: A 1:1,000-5,000 dilution of this antibody was used to detect SMAD4 in SHSY5Y cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon receipt and prior to removing the cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20°C. Avoid repeated freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.
SMAD4 is a member of the Mothers Against Dpp (MAD)-related family of proteins. SMAD4 is functionally distinct among the SMAD family, and is required for the assembly and transcriptional activation of diverse, SMAD-DNA complexes. SMAD4 appears to be not regulated by phosphorylation, but acts as a common mediator of TGF-β, activin, and bone morphogenetic protein signaling responses. SMAD4 is frequently inactivated in pancreatic, biliary and colorectal tumors.
Product Information
Format
Unpurified
Control
SHSY5Y cell lysate
Presentation
Rabbit Monoclonal in buffer containing 50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl containing 40% Glycerol, 0.01% sodium azide and 0.05% BSA.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target. Detect SMAD4 (C-term) using this Anti-SMAD4 (C-term) Antibody, clone EP618Y, Rabbit validated for use in WB, IH(P), IC, FC & IP.
Key Applications
Immunoprecipitation
Western Blotting
Immunohistochemistry (Paraffin)
Immunocytochemistry
Flow Cytometry
Application Notes
Immunohistochemistry Analysis (paraffin): A 1:100-250 dilution from a previous lot detected SMAD4 in human lung carcinoma tissue.
Immunocytochemistry Analysis: A 1:100-250 dilution from a previous lot detected SMAD4 in HeLa cells.
Flow Cytometry: A 1:20 dilution from a previous lot was used in FC.
Immunoprecipitation: A 1:30 dilution from a previous lot was used in IP.
Biological Information
Immunogen
Synthetic peptide corresponding to residues in the C-terminus of human SMAD4.
FUNCTION:Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. May act as a tumor suppressor. SUBUNIT STRUCTURE:May form trimers with receptor-regulated SMAD (R-SMAD). Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. SUBCELLULAR LOCATION:Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD. PTM:Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. INVOLVEMENT IN DISEASE:Defects in SMAD4 are a cause of pancreatic carcinoma [MIM:260350].
Defects in SMAD4 are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.
Defects in SMAD4 are a cause of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050]. JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic aetiology of this association is unknown.
Defects in SMAD4 may be a cause of colorectal cancer (CRC) [MIM:114500]. SEQUENCE SIMILARITIES:Belongs to the dwarfin/SMAD family.
Contains 1 MH1 (MAD homology 1) domain.
Contains 1 MH2 (MAD homology 2) domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blot on SHSY5Y cell lysates.
Western Blot Analysis: A 1:1,000-5,000 dilution of this antibody was used to detect SMAD4 in SHSY5Y cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon receipt and prior to removing the cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20°C. Avoid repeated freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.