Homo sapiens Gene: SMAD4
InnateDB Gene IDBG-3485.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SMAD4
Gene Name SMAD family member 4
Synonyms DPC4; JIP; MADH4; MYHRS;
Species Homo sapiens
Ensembl Gene ENSG00000141646
Encoded Proteins
SMAD family member 4
SMAD family member 4
SMAD family member 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
TGF-β signalling upregulates MIR181A2 expression through SMAD3/4-dependent promoter activation.
Entrez Gene
Summary This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to TGF-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Oct 2009]
Gene Information
Type Protein coding
Genomic Location Chromosome 18:51028394-51085045
Strand Forward strand
Band q21.2
ENST00000342988 ENSP00000341551
ENST00000398417 ENSP00000381452
ENST00000591914 ENSP00000466941
ENST00000592186 ENSP00000468611
ENST00000593223 ENSP00000466118
ENST00000589076 ENSP00000466934
ENST00000590061 ENSP00000464772
ENST00000588860 ENSP00000465878
ENST00000588745 ENSP00000464901
ENST00000589941 ENSP00000465874
ENST00000611848 ENSP00000478613
Number of Interactions This gene and/or its encoded proteins are associated with 364 experimentally validated interaction(s) in this database.
They are also associated with 39 interaction(s) predicted by orthology.
Experimentally validated
Total 364 [view]
Protein-Protein 345 [view]
Protein-DNA 16 [view]
Protein-RNA 0
DNA-DNA 3 [view]
Predicted by orthology
Total 39 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0000988 protein binding transcription factor activity
GO:0001076 RNA polymerase II transcription factor binding transcription factor activity
GO:0001085 RNA polymerase II transcription factor binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0005518 collagen binding
GO:0030616 transforming growth factor beta receptor, common-partner cytoplasmic mediator activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding
GO:0070411 I-SMAD binding
GO:0070412 R-SMAD binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0001702 gastrulation with mouth forming second
GO:0001822 kidney development
GO:0003190 atrioventricular valve formation
GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation
GO:0003251 positive regulation of cell proliferation involved in heart valve morphogenesis
GO:0003279 cardiac septum development
GO:0003360 brainstem development
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007183 SMAD protein complex assembly
GO:0007369 gastrulation
GO:0007411 axon guidance
GO:0007492 endoderm development
GO:0007498 mesoderm development
GO:0008283 cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0009952 anterior/posterior pattern specification
GO:0010467 gene expression
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0014033 neural crest cell differentiation
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0030308 negative regulation of cell growth
GO:0030509 BMP signaling pathway
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030513 positive regulation of BMP signaling pathway
GO:0032525 somite rostral/caudal axis specification
GO:0032909 regulation of transforming growth factor beta2 production
GO:0035556 intracellular signal transduction
GO:0036302 atrioventricular canal development
GO:0042118 endothelial cell activation
GO:0042127 regulation of cell proliferation
GO:0042177 negative regulation of protein catabolic process
GO:0045087 innate immune response (InnateDB)
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048589 developmental growth
GO:0048663 neuron fate commitment
GO:0048729 tissue morphogenesis
GO:0048733 sebaceous gland development
GO:0048859 formation of anatomical boundary
GO:0051098 regulation of binding
GO:0051797 regulation of hair follicle development
GO:0060021 palate development
GO:0060391 positive regulation of SMAD protein import into nucleus
GO:0060395 SMAD protein signal transduction
GO:0060548 negative regulation of cell death
GO:0060956 endocardial cell differentiation
GO:0071559 response to transforming growth factor beta
GO:0072133 metanephric mesenchyme morphogenesis
GO:0072134 nephrogenic mesenchyme morphogenesis
Cellular Component
GO:0000790 nuclear chromatin
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005829 cytosol
GO:0032444 activin responsive factor complex
GO:0071141 SMAD protein complex
Mus musculus
Bos taurus
Gene ID
Gene Order
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
TGF_beta_Receptor pathway
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway
SMAD4 MH2 Domain Mutants in Cancer pathway
Developmental Biology pathway
Transcriptional regulation of pluripotent stem cells pathway
Loss of Function of SMAD4 in Cancer pathway
Loss of Function of SMAD2/3 in Cancer pathway
Signaling by TGF-beta Receptor Complex in Cancer pathway
TGFBR2 MSI Frameshift Mutants in Cancer pathway
Signal Transduction pathway
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway
SMAD2/3 MH2 Domain Mutants in Cancer pathway
Loss of Function of TGFBR2 in Cancer pathway
Generic Transcription Pathway pathway
SMAD2/3 Phosphorylation Motif Mutants in Cancer pathway
TGFBR1 KD Mutants in Cancer pathway
Loss of Function of TGFBR1 in Cancer pathway
TGFBR1 LBD Mutants in Cancer pathway
Signaling by BMP pathway
Signaling by NODAL pathway
TGFBR2 Kinase Domain Mutants in Cancer pathway
TGF-beta receptor signaling activates SMADs pathway
Signaling by Activin pathway
Gene Expression pathway
Disease pathway
Signaling by TGF-beta Receptor Complex pathway
Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway
Cell cycle pathway
Wnt signaling pathway pathway
TGF-beta signaling pathway pathway
Adherens junction pathway
Pathways in cancer pathway
Colorectal cancer pathway
Pancreatic cancer pathway
Chronic myeloid leukemia pathway
TGF-beta signaling pathway
BMP2 signaling pathway
Wnt signaling pathway pathway
LIF signaling pathway
Cell cycle: g1/s check point [Biocarta view]
Tgf beta signaling pathway [Biocarta view]
Ctcf: first multivalent nuclear factor [Biocarta view]
Alk in cardiac myocytes [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
Wnt signaling pathway [Biocarta view]
ALK2 signaling events
BMP receptor signaling
Validated nuclear estrogen receptor alpha network
ALK1 signaling events
Validated targets of C-MYC transcriptional repression
Validated targets of C-MYC transcriptional activation
LKB1 signaling events
Regulation of nuclear SMAD2/3 signaling
HIF-1-alpha transcription factor network
TGF-beta receptor signaling
Regulation of cytoplasmic and nuclear SMAD2/3 signaling
UniProt Splice Variant
Entrez Gene 4089
UniGene Hs.610854 Hs.621831 Hs.707908 Hs.732302 Hs.75862
RefSeq NM_005359
OMIM 600993
HPRD 02995
EMBL AC087687 AC091551
RNA Seq Atlas 4089