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Identification
HMDB Protein ID HMDBP14469
Secondary Accession Numbers None
Name Mothers against decapentaplegic homolog 4
Synonyms
  1. MAD homolog 4
  2. Mothers against DPP homolog 4
  3. Deletion target in pancreatic carcinoma 4
  4. SMAD family member 4
  5. SMAD 4
  6. Smad4
  7. hSMAD4
Gene Name SMAD4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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 (PubMed:25514493). 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.
Pathways
  • Adherens junction
  • AGE-RAGE signaling pathway in diabetic complications
  • Apelin signaling pathway
  • Cell cycle
  • Chronic myeloid leukemia
  • Colorectal cancer
  • FoxO signaling pathway
  • Gastric cancer
  • Hepatitis B
  • Hepatocellular carcinoma
  • Hippo signaling pathway
  • Human T-cell leukemia virus 1 infection
  • Pancreatic cancer
  • Signaling pathways regulating pluripotency of stem cells
  • TGF-beta signaling pathway
  • Th17 cell differentiation
  • Wnt signaling pathway
Reactions Not Available
GO Classification
Biological Process
regulation of hair follicle development
spermatogenesis
ventricular septum morphogenesis
protein deubiquitination
somatic stem cell maintenance
cell proliferation
positive regulation of histone H3-K4 methylation
SMAD protein signal transduction
developmental growth
in utero embryonic development
BMP signaling pathway
anatomical structure morphogenesis
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of epithelial to mesenchymal transition
cellular iron ion homeostasis
epithelial to mesenchymal transition involved in endocardial cushion formation
positive regulation of pri-miRNA transcription by RNA polymerase II
regulation of binding
gastrulation with mouth forming second
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
negative regulation of BMP signaling pathway
endothelial cell activation
axon guidance
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
cell differentiation
branching involved in ureteric bud morphogenesis
neuron fate commitment
negative regulation of cardiac muscle hypertrophy
negative regulation of cell growth
atrioventricular canal development
atrioventricular valve formation
positive regulation of BMP signaling pathway
brainstem development
endocardial cell differentiation
female gonad morphogenesis
formation of anatomical boundary
left ventricular cardiac muscle tissue morphogenesis
mesendoderm development
metanephric mesenchyme morphogenesis
negative regulation of cardiac myofibril assembly
nephrogenic mesenchyme morphogenesis
neural crest cell differentiation
interleukin-6-mediated signaling pathway
outflow tract septum morphogenesis
positive regulation of cell proliferation involved in heart valve morphogenesis
positive regulation of follicle-stimulating hormone secretion
positive regulation of histone H3-K9 acetylation
positive regulation of luteinizing hormone secretion
positive regulation of SMAD protein signal transduction
positive regulation of transforming growth factor beta receptor signaling pathway
regulation of transforming growth factor beta receptor signaling pathway
regulation of transforming growth factor beta2 production
response to transforming growth factor beta
secondary palate development
seminiferous tubule development
SMAD protein complex assembly
transforming growth factor beta receptor signaling pathway
somite rostral/caudal axis specification
uterus development
negative regulation of cell proliferation
negative regulation of ERK1 and ERK2 cascade
negative regulation of cell death
sebaceous gland development
response to hypoxia
single fertilization
embryonic digit morphogenesis
cardiac conduction system development
cellular response to BMP stimulus
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
intracellular signal transduction
ovarian follicle development
Cellular Component
cytosol
centrosome
cytoplasm
nucleus
nucleoplasm
chromatin
activin responsive factor complex
heteromeric SMAD protein complex
SMAD protein complex
transcription factor complex
Molecular Function
metal ion binding
collagen binding
R-SMAD binding
DNA-binding transcription activator activity, RNA polymerase II-specific
chromatin binding
protein homodimerization activity
I-SMAD binding
RNA polymerase II transcription factor binding
transcription coactivator binding
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II core promoter proximal region sequence-specific DNA binding
identical protein binding
sulfate binding
transcription regulatory region sequence-specific DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 552
Molecular Weight 60438.705
Theoretical pI 6.984
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q13485
UniProtKB/Swiss-Prot Entry Name SMAD4_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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