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. 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. Belongs to the dwarfin/SMAD family. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Nuclear receptor co-regulator; Transcription, coactivator/corepressor
Chromosomal Location of mouse Ortholog: 18 E2|18 49.51 cM
Cellular Component:  activin responsive factor complex; centrosome; cytoplasm; cytosol; nuclear chromatin; nucleoplasm; nucleus; protein-containing complex; RNA polymerase II transcription factor complex; SMAD protein complex; transcription factor complex
Molecular Function:  chromatin binding; collagen binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; filamin binding; I-SMAD binding; identical protein binding; metal ion binding; molecular function regulator; protein binding; protein heterodimerization activity; protein homodimerization activity; proximal promoter sequence-specific DNA binding; R-SMAD binding; RNA polymerase II proximal promoter sequence-specific DNA binding; RNA polymerase II regulatory region sequence-specific DNA binding; RNA polymerase II transcription factor binding; SMAD binding; sulfate binding; transcription coregulator activity; transcription regulatory region DNA binding; transforming growth factor beta receptor, common-partner cytoplasmic mediator activity
Biological Process:  anatomical structure morphogenesis; anterior/posterior pattern specification; atrioventricular canal development; atrioventricular valve formation; axon guidance; BMP signaling pathway; brainstem development; branching involved in ureteric bud morphogenesis; cardiac septum development; cell differentiation; cell proliferation; cellular iron ion homeostasis; cellular response to glucose stimulus; developmental growth; embryonic digit morphogenesis; endocardial cell differentiation; endoderm development; endothelial cell activation; epithelial to mesenchymal transition involved in endocardial cushion formation; ERK1 and ERK2 cascade; female gonad development; female gonad morphogenesis; formation of anatomical boundary; gastrulation; gastrulation with mouth forming second; in utero embryonic development; interleukin-6-mediated signaling pathway; intracellular signal transduction; kidney development; left ventricular cardiac muscle tissue morphogenesis; male gonad development; mesendoderm development; 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 protein catabolic process; negative regulation of transcription by RNA polymerase II; negative regulation of transcription, DNA-templated; nephrogenic mesenchyme morphogenesis; neural crest cell differentiation; neuron fate commitment; osteoblast differentiation; outflow tract septum morphogenesis; ovarian follicle development; positive regulation of BMP signaling pathway; positive regulation of cardiac muscle cell apoptotic process; 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 signal transduction; positive regulation of transcription by RNA polymerase II; positive regulation of transcription, DNA-templated; positive regulation of transforming growth factor beta receptor signaling pathway; pri-miRNA transcription by RNA polymerase II; protein homotrimerization; regulation of binding; regulation of cell proliferation; regulation of hair follicle development; regulation of transcription by RNA polymerase II; regulation of transcription, DNA-templated; regulation of transforming growth factor beta receptor signaling pathway; regulation of transforming growth factor beta2 production; response to hypoxia; response to transforming growth factor beta; sebaceous gland development; secondary palate development; seminiferous tubule development; single fertilization; SMAD protein complex assembly; SMAD protein signal transduction; somite rostral/caudal axis specification; spermatogenesis; tissue morphogenesis; transforming growth factor beta receptor signaling pathway; uterus development; ventricular septum morphogenesis; wound healing
Reference #:  P97471 (UniProtKB)
Alt. Names/Synonyms: AW743858; D18Wsu70; D18Wsu70e; Deletion target in pancreatic carcinoma 4 homolog; DPC; Dpc4; MAD homolog 4; MAD homolog 4 (Drosophila); Madh; Madh4; Mothers against decapentaplegic homolog 4; Mothers against DPP homolog 4; OTTMUSP00000023201; OTTMUSP00000023202; SMAD 4; SMAD family member 4; Smad4
Gene Symbols: Smad4
Molecular weight: 60,342 Da
Basal Isoelectric point: 6.5  Predict pI for various phosphorylation states
CST Pathways:  ESC Pluripotency and Differentiation  |  G1/S Checkpoint  |  SAPK/JNK Signaling Cascades  |  TGF-ß Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene  |  NURSA