The Function of SMAD4
In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
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Protein names
Recommended name:
Mothers against decapentaplegic homolog 4Alternative name(s):
MAD homolog 4Mothers against DPP homolog 4
Deletion target in pancreatic carcinoma 4
SMAD family member 4
SMAD 4
Smad4
hSMAD4
Top Gene-Substance Interactions
SMAD4 Interacts with These Diseases
| Disease | Score |
Substances That Increase SMAD4
| Substances | Interaction | Organism | Category |
Substances That Decrease SMAD4
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
Molecular Function:
- Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
- Core Promoter Proximal Region Sequence-Specific Dna Binding
- Transcription Factor Activity, Rna Polymerase Ii Transcription Factor Binding
- Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
- Chromatin Binding
- Transforming Growth Factor Beta Receptor, Common-Partner Cytoplasmic Mediator Activity
- Identical Protein Binding
- Protein Homodimerization Activity
- Transcription Regulatory Region Dna Binding
- Metal Ion Binding
- I-Smad Binding
- R-Smad Binding
Biological Processes:
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Ovarian Follicle Development
- Branching Involved In Ureteric Bud Morphogenesis
- Response To Hypoxia
- In Utero Embryonic Development
- Gastrulation With Mouth Forming Second
- Outflow Tract Septum Morphogenesis
- Atrioventricular Valve Formation
- Epithelial To Mesenchymal Transition Involved In Endocardial Cushion Formation
- Left Ventricular Cardiac Muscle Tissue Morphogenesis
- Positive Regulation Of Cell Proliferation Involved In Heart Valve Morphogenesis
- Brainstem Development
- Cellular Iron Ion Homeostasis
- Transforming Growth Factor Beta Receptor Signaling Pathway
- Smad Protein Complex Assembly
- Spermatogenesis
- Single Fertilization
- Axon Guidance
- Endoderm Development
- Mesoderm Development
- Cell Proliferation
- Negative Regulation Of Cell Proliferation
- Negative Regulation Of Cardiac Muscle Hypertrophy
- Positive Regulation Of Epithelial To Mesenchymal Transition
- Positive Regulation Of Pathway-Restricted Smad Protein Phosphorylation
- Neural Crest Cell Differentiation
- Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
- Negative Regulation Of Cell Growth
- Bmp Signaling Pathway
- Positive Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
- Positive Regulation Of Bmp Signaling Pathway
- Somite Rostral/Caudal Axis Specification
- Regulation Of Transforming Growth Factor Beta2 Production
- Positive Regulation Of Luteinizing Hormone Secretion
- Somatic Stem Cell Population Maintenance
- Intracellular Signal Transduction
- Atrioventricular Canal Development
- Endothelial Cell Activation
- Embryonic Digit Morphogenesis
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Follicle-Stimulating Hormone Secretion
- Developmental Growth
- Neuron Fate Commitment
- Sebaceous Gland Development
- Formation Of Anatomical Boundary
- Regulation Of Binding
- Positive Regulation Of Histone H3-K4 Methylation
- Regulation Of Hair Follicle Development
- Palate Development
- Uterus Development
- Positive Regulation Of Smad Protein Import Into Nucleus
- Smad Protein Signal Transduction
- Ventricular Septum Morphogenesis
- Negative Regulation Of Cell Death
- Endocardial Cell Differentiation
- Female Gonad Morphogenesis
- Interleukin-6-Mediated Signaling Pathway
- Negative Regulation Of Erk1 And Erk2 Cascade
- Response To Transforming Growth Factor Beta
- Cellular Response To Bmp Stimulus
- Metanephric Mesenchyme Morphogenesis
- Nephrogenic Mesenchyme Morphogenesis
- Seminiferous Tubule Development
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Cellular Response To Chemical Stimulus
- Negative Regulation Of Cardiac Myofibril Assembly
- Positive Regulation Of Histone H3-K9 Acetylation