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  3. SMAD4

SMAD4 (SMAD family member 4)

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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 4

Alternative name(s):

MAD homolog 4
Mothers 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

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • AP-1
  • c-Jun
  • Nkx2-5
  • C/EBPbeta
  • C/EBPalpha
  • STAT5A
  • E2F-4
  • E2F-5
  • p300

Gene Pathways:

  • Disease
  • Pathways in cancer
  • Signal Transduction
  • Gene Expression
  • Wnt signaling pathway
  • Adherens junction
  • Colorectal cancer
  • TGF-beta signaling pathway
  • Chronic myeloid leukemia
  • Pancreatic cancer

Molecular Function:

  • Chromatin Binding
  • Core Promoter Proximal Region Sequence-Specific Dna Binding
  • Identical Protein Binding
  • I-Smad Binding
  • Metal Ion Binding
  • Protein Homodimerization Activity
  • Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
  • R-Smad Binding
  • Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
  • Transcription Factor Activity, Rna Polymerase Ii Transcription Factor Binding
  • Transcription Regulatory Region Dna Binding
  • Transforming Growth Factor Beta Receptor, Common-Partner Cytoplasmic Mediator Activity

Biological Processes:

  • Atrioventricular Canal Development
  • Atrioventricular Valve Formation
  • Axon Guidance
  • Bmp Signaling Pathway
  • Brainstem Development
  • Branching Involved In Ureteric Bud Morphogenesis
  • Cell Proliferation
  • Cellular Iron Ion Homeostasis
  • Cellular Response To Bmp Stimulus
  • Developmental Growth
  • Embryonic Digit Morphogenesis
  • Endocardial Cell Differentiation
  • Endoderm Development
  • Endothelial Cell Activation
  • Epithelial To Mesenchymal Transition Involved In Endocardial Cushion Formation
  • Female Gonad Morphogenesis
  • Formation Of Anatomical Boundary
  • Gastrulation With Mouth Forming Second
  • Interleukin-6-Mediated Signaling Pathway
  • Intracellular Signal Transduction
  • In Utero Embryonic Development
  • Left Ventricular Cardiac Muscle Tissue Morphogenesis
  • Mesoderm Development
  • Metanephric Mesenchyme Morphogenesis
  • Negative Regulation Of Cardiac Muscle Hypertrophy
  • Negative Regulation Of Cardiac Myofibril Assembly
  • Negative Regulation Of Cell Death
  • Negative Regulation Of Cell Growth
  • Negative Regulation Of Cell Proliferation
  • Negative Regulation Of Erk1 And Erk2 Cascade
  • Negative Regulation Of Transcription, Dna-Templated
  • Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Nephrogenic Mesenchyme Morphogenesis
  • Neural Crest Cell Differentiation
  • Neuron Fate Commitment
  • Outflow Tract Septum Morphogenesis
  • Ovarian Follicle Development
  • Palate Development
  • Positive Regulation Of Bmp Signaling Pathway
  • Positive Regulation Of Cell Proliferation Involved In Heart Valve Morphogenesis
  • Positive Regulation Of Epithelial To Mesenchymal Transition
  • Positive Regulation Of Follicle-Stimulating Hormone Secretion
  • Positive Regulation Of Histone H3-K4 Methylation
  • Positive Regulation Of Histone H3-K9 Acetylation
  • Positive Regulation Of Luteinizing Hormone Secretion
  • Positive Regulation Of Pathway-Restricted Smad Protein Phosphorylation
  • Positive Regulation Of Smad Protein Import Into Nucleus
  • Positive Regulation Of Transcription, Dna-Templated
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Cellular Response To Chemical Stimulus
  • Positive Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
  • Regulation Of Binding
  • Regulation Of Hair Follicle Development
  • Regulation Of Transforming Growth Factor Beta2 Production
  • Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
  • Response To Hypoxia
  • Response To Transforming Growth Factor Beta
  • Sebaceous Gland Development
  • Seminiferous Tubule Development
  • Single Fertilization
  • Smad Protein Complex Assembly
  • Smad Protein Signal Transduction
  • Somatic Stem Cell Population Maintenance
  • Somite Rostral/Caudal Axis Specification
  • Spermatogenesis
  • Transforming Growth Factor Beta Receptor Signaling Pathway
  • Uterus Development
  • Ventricular Septum Morphogenesis
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

Anapl_13087| AS27_08665| CB1_000632005| D18Wsu70e| D623_10005924| deleted in pancreatic carcinoma locus 4| deletion target in pancreatic carcinoma 4| deletion target in pancreatic carcinoma 4 homolog| DPC4| EGK_09691| GW7_16263| H920_04224| I79_014292| JIP| M959_04088| Madh4| MAD homolog 4| MAD homolog 4 (Drosophila)| MAD (mothers against decapentaplegic Drosophila) homolog 4| MAD, mothers against decapentaplegic homolog 4| MDA_GLEAN10011882| Mothers against decapentaplegic 4| Mothers against decapentaplegic-4| Mothers against decapentaplegic 4 (SMAD 4)-like protein| mothers against decapentaplegic, Drosophila, homolog of, 4| Mothers against decapentaplegic homolog 4| Mothers against decapentaplegic-like 4| mothers against decapentaplegic-like 4-like protein| Mothers against decapentaplegic like protein 4| Mothers against decapentaplegic-like protein 4| mothers against decapentaplegic-like protein 4-like protein| mothers against DPP homolog 4| mothers against DPP-like 4| MYHRS| N301_04491| N302_07758| N305_08568| N309_14831| N320_09939| N321_10030| N328_06411| N329_00979| N334_07545| N335_07211| N336_09922| N340_09358| PAL_GLEAN10023027| PANDA_004946| protein unc-50 homolog| SMAD 4| Smad4 protein| SMAD, mothers against DPP homolog 4| TREES_T100012360| UY3_10806| Y1Q_000274| smad4

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