Harmonizome 3.0

SMAD family member 4

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 transforming growth factor (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 protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasing blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. 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, May 2022]

From ChEA Transcription Factor Targets

target genes of the SMAD4 transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.

From GeneRIF Biological Term Annotations

genes co-occuring with the biological term smad4 in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.

From Hub Proteins Protein-Protein Interactions

interacting proteins for hub protein SMAD4 from the curated Hub Proteins Protein-Protein Interactions dataset.

From MotifMap Predicted Transcription Factor Targets

target genes of the SMAD4 transcription factor predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.

From Pathway Commons Protein-Protein Interactions

interacting proteins for SMAD4 from the Pathway Commons Protein-Protein Interactions dataset.

From LINCS L1000 CMAP CRISPR Knockout Consensus Signatures

genes differentially expressed following the SMAD4 gene perturbation from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.

From JASPAR Predicted Mouse Transcription Factor Targets 2025

target genes of the Smad4 transcription factor predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2925 dataset.

From CM4AI KOLF21J CRISPRi Gene Perturbation Atlas

genes differentially expressed following the SMAD4 gene perturbation from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas.

From ChEA Transcription Factor Binding Site Profiles

genes with transcription factor binding evidence in the SMAD4-19686287-HaCaT-human transcription factor binding site profile from the CHEA Transcription Factor Binding Site Profiles dataset.

From ChEA Transcription Factor Binding Site Profiles

genes with transcription factor binding evidence in the SMAD4-21741376-HESC-HUMAN transcription factor binding site profile from the CHEA Transcription Factor Binding Site Profiles dataset.

From ChEA Transcription Factor Binding Site Profiles

genes with transcription factor binding evidence in the SMAD4-21799915-A2780-HUMAN transcription factor binding site profile from the CHEA Transcription Factor Binding Site Profiles dataset.

From COMPARTMENTS Text-mining Protein Localization Evidence Scores

proteins co-occuring with the smad2-smad4 protein complex cellular component in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.

From COMPARTMENTS Text-mining Protein Localization Evidence Scores

proteins co-occuring with the smad3-smad4 protein complex cellular component in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.

From CORUM Protein Complexes

proteins in the SMAD4-SKI complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SKI-SMAD2-SMAD4 pentameric complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the Ectodermin-SMAD4 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-cJUN complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD4-SNO-SKI complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-cSKI, TGF(beta)-dependent protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the Smad3-Smad4 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD2-SMAD4-FAST1 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-FOXO4 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the JUND-FOSB-SMAD3-SMAD4 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the Smad2-Smad4 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-FOXO1 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the CREBBP-SMAD3-SMAD4 pentameric complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-FOXO3 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-FOXO3-FOXG1 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the Ecsit complex (Ecsit2-Smad4) protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-CTCF protein-DNA complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SKI-SMAD3-SMAD4 pentameric complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the CREBBP-SMAD2-SMAD4 pentameric complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-SP1 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the Ecsit complex (Smad1-Smad4-Ecsit2) protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD4-SMAD2-SMAD3 complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD3-SMAD4-cJun-cFos complex protein complex from the CORUM Protein Complexes dataset.

From CORUM Protein Complexes

proteins in the SMAD4-SKI-NCOR complex protein complex from the CORUM Protein Complexes dataset.

From GO Cellular Component Annotations 2015

proteins localized to the smad3-smad4 protein complex cellular component from the curated GO Cellular Component Annotations 2015 dataset.

From InterPro Predicted Protein Domain Annotations

proteins predicted to have the c-SKI SMAD4-binding domain protein domain from the InterPro Predicted Protein Domain Annotations dataset.

From Reactome Pathways 2014

proteins participating in the Loss of Function of SMAD4 in Cancer pathway from the Reactome Pathways dataset.

From Reactome Pathways 2014

proteins participating in the SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway from the Reactome Pathways dataset.

From Reactome Pathways 2014

proteins participating in the Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway from the Reactome Pathways dataset.

From Reactome Pathways 2014

proteins participating in the Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway from the Reactome Pathways dataset.

From Reactome Pathways 2014

proteins participating in the SMAD4 MH2 Domain Mutants in Cancer pathway from the Reactome Pathways dataset.

From DisGeNET Gene-Disease Associations

genes associated with the disease Smad4-Related Juvenile Polyposis in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.

From ChEA Transcription Factor Targets 2022

target genes of the SMAD4-19686287-HACAT-HUMAN transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.

From ChEA Transcription Factor Targets 2022

target genes of the SMAD4-21741376-ESCS-HUMAN transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.

From ChEA Transcription Factor Targets 2022

target genes of the SMAD4-21741376-EPCS-HUMAN transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.

From ChEA Transcription Factor Targets 2022

target genes of the SMAD4-21799915-A2780-HUMAN transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.

From ChEA Transcription Factor Targets 2022

target genes of the SMAD4-21741376-HESCS-HUMAN transcription factor in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.

From Reactome Pathways 2024

proteins participating in the Downregulation of SMAD2/3:SMAD4 transcriptional activity pathway from the Reactome Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the Loss of Function of SMAD4 in Cancer pathway from the Reactome Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription pathway from the Reactome Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the SMAD4 MH2 Domain Mutants in Cancer pathway from the Reactome Pathways 2024 dataset.

From Reactome Pathways 2024

proteins participating in the Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer pathway from the Reactome Pathways 2024 dataset.