Summary

Name SMAD4
Full Name Mothers against decapentaplegic homolog 4
Synonyms MAD homolog 4, Mothers against DPP homolog 4, Deletion target in pancreatic carcinoma 4, SMAD family member 4, SMAD 4, Smad4, hSMAD4 | DPC4, MADH4
Primary ID Q13485
Links - -
Type protein
Relations 41
Pathways TGFbeta Signaling, Colorectal Carcinoma
Function 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.

Viewer

Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png sumoylation SMAD4 0.22
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png deubiquitination SMAD4 0.44
Publications: 3 Organism: Mus Musculus, Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SMAD4 0.22
Publications: 1 Organism: Homo Sapiens
Pathways:Colorectal Carcinoma
+ up-regulates img/direct-activation.png phosphorylation SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD1/5/8/SMAD4 0.2
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination SMAD4 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding SMAD4 0.55
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates img/direct-activation.png phosphorylation SMAD4 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination SMAD4 0.34
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination SMAD4 0.22
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates img/direct-activation.png phosphorylation SMAD4 0.36
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD5/SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD8/SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding SMAD4 0.4
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ down-regulates activity img/direct_inhibition.png binding SMAD4 0.51
Publications: 2 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates activity img/direct-activation.png binding SMAD4 0.35
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates activity img/direct-activation.png binding SMAD4 0.76
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ down-regulates img/direct_inhibition.png ubiquitination SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png ubiquitination SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD3/SMAD4 0.28
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ up-regulates img/direct-activation.png binding SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation, binding SMAD4 0.58
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD2/SMAD4 0.31
Publications: 1 Organism: Homo Sapiens
Pathways:TGFbeta Signaling
+ down-regulates activity img/direct_inhibition.png ubiquitination SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/direct_inhibition.png transcriptional regulation MYC 0.22
Publications: 1 Organism: Homo Sapiens
Pathways:Colorectal Carcinoma
+ down-regulates img/direct_inhibition.png binding SMAD4 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png sumoylation SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png relocalization SMAD4 0.14
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding SMAD4/JUN 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png LEF1 0.22
Publications: 1 Organism: Homo Sapiens
Pathways:Colorectal Carcinoma
+ form complex img/form-complex.png binding SMAD1/4 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding SMAD4 0.78
Publications: 1 Organism: Homo Sapiens
Pathways:Colorectal Carcinoma, TGFbeta Signaling