Gene description for Smad4
Gene name SMAD family member 4
Gene symbol Smad4
Other names/aliases AW743858
D18Wsu70e
DPC4
Madh4
Species Mus musculus
 Database cross references - Smad4
ExoCarta ExoCarta_17128
Vesiclepedia VP_17128
Entrez Gene 17128
UniProt P97471  
 Smad4 identified in sEVs derived from the following tissue/cell type
Mast cells 17486113    
 Gene ontology annotations for Smad4
Molecular Function
    transcription cis-regulatory region binding GO:0000976 ISO
    RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0000977 IDA
    RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0000977 IGI
    RNA polymerase II cis-regulatory region sequence-specific DNA binding GO:0000978 IBA
    RNA polymerase II cis-regulatory region sequence-specific DNA binding GO:0000978 IDA
    RNA polymerase II cis-regulatory region sequence-specific DNA binding GO:0000978 ISO
    DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 IBA
    transcription corepressor binding GO:0001222 IEA
    transcription corepressor binding GO:0001222 ISO
    transcription coactivator binding GO:0001223 IEA
    transcription coactivator binding GO:0001223 ISO
    DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 IDA
    DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 IGI
    DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 ISO
    DNA binding GO:0003677 IDA
    DNA binding GO:0003677 ISO
    DNA binding GO:0003677 ISO
    chromatin binding GO:0003682 IDA
    DNA-binding transcription factor activity GO:0003700 IDA
    DNA-binding transcription factor activity GO:0003700 ISO
    DNA-binding transcription factor activity GO:0003700 ISO
    protein binding GO:0005515 IPI
    collagen binding GO:0005518 IPI
    filamin binding GO:0031005 IEA
    filamin binding GO:0031005 ISO
    identical protein binding GO:0042802 IPI
    identical protein binding GO:0042802 ISO
    protein homodimerization activity GO:0042803 IEA
    protein homodimerization activity GO:0042803 ISO
    sulfate binding GO:0043199 IEA
    sulfate binding GO:0043199 ISO
    sequence-specific DNA binding GO:0043565 ISO
    protein-containing complex binding GO:0044877 ISO
    SMAD binding GO:0046332 ISO
    metal ion binding GO:0046872 IEA
    RNA polymerase II-specific DNA-binding transcription factor binding GO:0061629 IPI
    I-SMAD binding GO:0070411 IBA
    I-SMAD binding GO:0070411 IEA
    I-SMAD binding GO:0070411 ISO
    R-SMAD binding GO:0070412 IEA
    R-SMAD binding GO:0070412 ISO
Biological Process
    negative regulation of transcription by RNA polymerase II GO:0000122 IMP
    negative regulation of transcription by RNA polymerase II GO:0000122 IMP
    ovarian follicle development GO:0001541 IGI
    ovarian follicle development GO:0001541 IMP
    osteoblast differentiation GO:0001649 IEA
    osteoblast differentiation GO:0001649 ISO
    branching involved in ureteric bud morphogenesis GO:0001658 IGI
    response to hypoxia GO:0001666 IEA
    response to hypoxia GO:0001666 ISO
    in utero embryonic development GO:0001701 IMP
    gastrulation with mouth forming second GO:0001702 IMP
    kidney development GO:0001822 IMP
    epithelial to mesenchymal transition GO:0001837 ISO
    outflow tract septum morphogenesis GO:0003148 IGI
    atrioventricular valve formation GO:0003190 IGI
    epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 IMP
    left ventricular cardiac muscle tissue morphogenesis GO:0003220 IMP
    positive regulation of cell proliferation involved in heart valve morphogenesis GO:0003251 IMP
    cardiac septum development GO:0003279 IGI
    brainstem development GO:0003360 IMP
    DNA-templated transcription GO:0006351 ISO
    regulation of DNA-templated transcription GO:0006355 NAS
    regulation of transcription by RNA polymerase II GO:0006357 IBA
    regulation of transcription by RNA polymerase II GO:0006357 IDA
    transcription by RNA polymerase II GO:0006366 IMP
    intracellular iron ion homeostasis GO:0006879 IMP
    transforming growth factor beta receptor signaling pathway GO:0007179 IBA
    transforming growth factor beta receptor signaling pathway GO:0007179 IGI
    transforming growth factor beta receptor signaling pathway GO:0007179 IMP
    transforming growth factor beta receptor signaling pathway GO:0007179 ISO
    transforming growth factor beta receptor signaling pathway GO:0007179 NAS
    spermatogenesis GO:0007283 IMP
    single fertilization GO:0007338 IGI
    gastrulation GO:0007369 IMP
    axon guidance GO:0007411 IMP
    endoderm development GO:0007492 IMP
    mesoderm development GO:0007498 IMP
    cell population proliferation GO:0008283 IGI
    cell population proliferation GO:0008283 IMP
    negative regulation of cell population proliferation GO:0008285 IGI
    male gonad development GO:0008584 IMP
    female gonad development GO:0008585 IGI
    anatomical structure morphogenesis GO:0009653 IBA
    anatomical structure morphogenesis GO:0009653 IMP
    anterior/posterior pattern specification GO:0009952 IMP
    negative regulation of cardiac muscle hypertrophy GO:0010614 IMP
    positive regulation of gene expression GO:0010628 IEA
    positive regulation of gene expression GO:0010628 ISO
    epithelial cell migration GO:0010631 IEA
    epithelial cell migration GO:0010631 ISO
    positive regulation of cardiac muscle cell apoptotic process GO:0010666 IEA
    positive regulation of cardiac muscle cell apoptotic process GO:0010666 ISO
    positive regulation of epithelial to mesenchymal transition GO:0010718 IMP
    neural crest cell differentiation GO:0014033 IMP
    cardiac muscle hypertrophy in response to stress GO:0014898 IEA
    cardiac muscle hypertrophy in response to stress GO:0014898 ISO
    cell differentiation GO:0030154 IBA
    cell differentiation GO:0030154 IMP
    negative regulation of cell growth GO:0030308 IEA
    negative regulation of cell growth GO:0030308 ISO
    adrenal gland development GO:0030325 IEA
    BMP signaling pathway GO:0030509 IBA
    BMP signaling pathway GO:0030509 IMP
    BMP signaling pathway GO:0030509 ISO
    positive regulation of transforming growth factor beta receptor signaling pathway GO:0030511 IEA
    positive regulation of transforming growth factor beta receptor signaling pathway GO:0030511 ISO
    somite rostral/caudal axis specification GO:0032525 IMP
    regulation of transforming growth factor beta2 production GO:0032909 IEA
    regulation of transforming growth factor beta2 production GO:0032909 ISO
    activin receptor signaling pathway GO:0032924 NAS
    positive regulation of luteinizing hormone secretion GO:0033686 IGI
    positive regulation of luteinizing hormone secretion GO:0033686 IMP
    intracellular signal transduction GO:0035556 ISO
    atrioventricular canal development GO:0036302 IGI
    endothelial cell activation GO:0042118 IMP
    regulation of cell population proliferation GO:0042127 IGI
    regulation of cell population proliferation GO:0042127 IMP
    negative regulation of protein catabolic process GO:0042177 IEA
    negative regulation of protein catabolic process GO:0042177 ISO
    embryonic digit morphogenesis GO:0042733 IMP
    negative regulation of DNA-templated transcription GO:0045892 ISO
    positive regulation of DNA-templated transcription GO:0045893 IDA
    positive regulation of DNA-templated transcription GO:0045893 ISO
    positive regulation of transcription by RNA polymerase II GO:0045944 IDA
    positive regulation of transcription by RNA polymerase II GO:0045944 IDA
    positive regulation of transcription by RNA polymerase II GO:0045944 IGI
    positive regulation of transcription by RNA polymerase II GO:0045944 IMP
    positive regulation of transcription by RNA polymerase II GO:0045944 IMP
    positive regulation of transcription by RNA polymerase II GO:0045944 ISO
    positive regulation of follicle-stimulating hormone secretion GO:0046881 IGI
    positive regulation of follicle-stimulating hormone secretion GO:0046881 IMP
    mesendoderm development GO:0048382 IMP
    developmental growth GO:0048589 IMP
    neuron fate commitment GO:0048663 IMP
    neuron fate specification GO:0048665 IEA
    neuron fate specification GO:0048665 ISO
    tissue morphogenesis GO:0048729 IMP
    sebaceous gland development GO:0048733 IMP
    formation of anatomical boundary GO:0048859 IMP
    regulation of binding GO:0051098 IDA
    regulation of hair follicle development GO:0051797 IMP
    uterus development GO:0060065 IGI
    positive regulation of SMAD protein signal transduction GO:0060391 IMP
    SMAD protein signal transduction GO:0060395 IBA
    SMAD protein signal transduction GO:0060395 IMP
    SMAD protein signal transduction GO:0060395 IMP
    SMAD protein signal transduction GO:0060395 ISO
    ventricular septum morphogenesis GO:0060412 IMP
    endocardial cell differentiation GO:0060956 IMP
    female gonad morphogenesis GO:0061040 IMP
    secondary palate development GO:0062009 IMP
    interleukin-6-mediated signaling pathway GO:0070102 IDA
    ERK1 and ERK2 cascade GO:0070371 IEA
    ERK1 and ERK2 cascade GO:0070371 ISO
    negative regulation of ERK1 and ERK2 cascade GO:0070373 IMP
    cellular response to glucose stimulus GO:0071333 IEA
    cellular response to glucose stimulus GO:0071333 ISO
    response to transforming growth factor beta GO:0071559 ISO
    cellular response to transforming growth factor beta stimulus GO:0071560 ISO
    metanephric mesenchyme morphogenesis GO:0072133 IMP
    nephrogenic mesenchyme morphogenesis GO:0072134 IMP
    seminiferous tubule development GO:0072520 IMP
    negative regulation of canonical Wnt signaling pathway GO:0090090 IEA
    negative regulation of canonical Wnt signaling pathway GO:0090090 ISO
    extrinsic apoptotic signaling pathway GO:0097191 IEA
    extrinsic apoptotic signaling pathway GO:0097191 ISO
    positive regulation of extracellular matrix assembly GO:1901203 IEA
    positive regulation of extracellular matrix assembly GO:1901203 ISO
    positive regulation of miRNA transcription GO:1902895 IMP
    negative regulation of cardiac myofibril assembly GO:1905305 IMP
Subcellular Localization
    chromatin GO:0000785 IEA
    chromatin GO:0000785 ISO
    nucleus GO:0005634 IDA
    nucleus GO:0005634 ISO
    nucleoplasm GO:0005654 ISO
    nucleoplasm GO:0005654 TAS
    transcription regulator complex GO:0005667 IPI
    transcription regulator complex GO:0005667 ISO
    cytoplasm GO:0005737 IDA
    cytoplasm GO:0005737 ISO
    centrosome GO:0005813 IEA
    centrosome GO:0005813 ISO
    cytosol GO:0005829 IEA
    cytosol GO:0005829 ISO
    activin responsive factor complex GO:0032444 IEA
    activin responsive factor complex GO:0032444 ISO
    protein-containing complex GO:0032991 ISO
    SMAD protein complex GO:0071141 ISO
    heteromeric SMAD protein complex GO:0071144 IBA
    heteromeric SMAD protein complex GO:0071144 ISO
    heteromeric SMAD protein complex GO:0071144 NAS
    RNA polymerase II transcription regulator complex GO:0090575 IDA
 Experiment description of studies that identified Smad4 in sEVs
1
Experiment ID 15
MISEV standards
EM
Biophysical techniques
CD63
Enriched markers
Negative markers
Particle analysis
Identified molecule mrna
Identification method Microarray
PubMed ID 17486113    
Organism Mus musculus
Homo sapiens
Experiment description Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
Authors "Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO"
Journal name NCB
Publication year 2007
Sample Mast cells
Sample name MC9
Bone marrow-derived mast cells
HMC-1
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.11-1.21 g/mL
Molecules identified in the study Protein
mRNA
miRNA
Methods used in the study Mass spectrometry [MALDI TOF]
Western blotting
Microarray
miRCURY LNA Array
 Protein-protein interactions for Smad4
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 Lef1 16842
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Synthetic Growth Defect Mus musculus
2 Gata5  
Reconstituted Complex Mus musculus
3 Btrc  
Affinity Capture-Western Mus musculus
4 Eif4enif1  
Affinity Capture-Western Mus musculus
5 Pknox1  
Affinity Capture-Western Mus musculus
6 Mfn2  
Co-fractionation Mus musculus
7 Pex6  
Affinity Capture-Western Mus musculus
8 Sin3a  
Affinity Capture-Western Mus musculus
9 Smad4 17128
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
10 Smad3  
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Reconstituted Complex Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
11 Ddx5 13207
Affinity Capture-Western Mus musculus
12 Smad2  
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
Affinity Capture-Western Mus musculus
13 Col1a1 12842
Affinity Capture-Western Mus musculus
14 Foxp1  
Two-hybrid Mus musculus
15 Snai1  
Affinity Capture-Western Mus musculus
16 Pbx1  
Affinity Capture-Western Mus musculus
17 Col5a1 12831
Affinity Capture-Western Mus musculus
18 Zmym2  
Affinity Capture-Western Mus musculus
19 Smarcd3  
Affinity Capture-Western Mus musculus
20 Hdac1 433759
Affinity Capture-Western Mus musculus
21 Col3a1 12825
Affinity Capture-Western Mus musculus
22 Tlx3  
Two-hybrid Mus musculus
23 Prkar1b  
Co-fractionation Mus musculus
24 Gata6  
Reconstituted Complex Mus musculus
25 Gata4  
Affinity Capture-Western Mus musculus
Reconstituted Complex Mus musculus
Two-hybrid Mus musculus
Reconstituted Complex Mus musculus
26 Sf3b2  
Affinity Capture-Western Mus musculus
27 Atg12  
Negative Genetic Mus musculus
28 Gadd45a  
Reconstituted Complex Mus musculus
29 Apc  
Phenotypic Enhancement Mus musculus
Phenotypic Enhancement Mus musculus
Phenotypic Enhancement Mus musculus
Phenotypic Enhancement Mus musculus
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