SMAD2
SMAD family member 2 | JV18-1, MADR2, MADH2

The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

Member of: DE-4 Developmental clusters: GC6
Biological processes 113 terms
DNA binding (GO:0003677)DNA binding (GO:0003677)DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228)DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228)DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228)DNA-binding transcription factor activity (GO:0003700)DNA-binding transcription factor activity (GO:0003700)DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)DNA-binding transcription factor binding (GO:0140297)DNA-binding transcription factor binding (GO:0140297)DNA-templated transcription (GO:0006351)I-SMAD binding (GO:0070411)I-SMAD binding (GO:0070411)R-SMAD binding (GO:0070412)RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)SMAD binding (GO:0046332)SMAD binding (GO:0046332)SMAD protein complex (GO:0071141)SMAD protein signal transduction (GO:0060395)SMAD protein signal transduction (GO:0060395)SMAD protein signal transduction (GO:0060395)SMAD protein signal transduction (GO:0060395)SMAD protein signal transduction (GO:0060395)activin receptor signaling pathway (GO:0032924)activin receptor signaling pathway (GO:0032924)activin receptor signaling pathway (GO:0032924)activin responsive factor complex (GO:0032444)anatomical structure morphogenesis (GO:0009653)anterior/posterior pattern specification (GO:0009952)aortic valve morphogenesis (GO:0003180)aortic valve morphogenesis (GO:0003180)cell differentiation (GO:0030154)cell fate commitment (GO:0045165)chromatin (GO:0000785)chromatin (GO:0000785)chromatin binding (GO:0003682)cis-regulatory region sequence-specific DNA binding (GO:0000987)co-SMAD binding (GO:0070410)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)determination of left/right asymmetry in lateral mesoderm (GO:0003140)disordered domain specific binding (GO:0097718)double-stranded DNA binding (GO:0003690)double-stranded DNA binding (GO:0003690)embryonic pattern specification (GO:0009880)endocardial cushion morphogenesis (GO:0003203)endocardial cushion morphogenesis (GO:0003203)gastrulation (GO:0007369)gastrulation (GO:0007369)heteromeric SMAD protein complex (GO:0071144)heteromeric SMAD protein complex (GO:0071144)identical protein binding (GO:0042802)identical protein binding (GO:0042802)intracellular signal transduction (GO:0035556)mesenchyme development (GO:0060485)mesoderm development (GO:0007498)mesoderm formation (GO:0001707)negative regulation of DNA-templated transcription (GO:0045892)negative regulation of cell differentiation (GO:0045596)negative regulation of gene expression (GO:0010629)negative regulation of ossification (GO:0030279)nodal signaling pathway (GO:0038092)nucleolus (GO:0005730)nucleoplasm (GO:0005654)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)odontoblast differentiation (GO:0071895)odontoblast differentiation (GO:0071895)paraxial mesoderm morphogenesis (GO:0048340)phosphatase binding (GO:0019902)positive regulation of BMP signaling pathway (GO:0030513)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of epithelial to mesenchymal transition (GO:0010718)positive regulation of epithelial to mesenchymal transition (GO:0010718)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)primary miRNA processing (GO:0031053)protein binding (GO:0005515)protein-containing complex (GO:0032991)pulmonary valve morphogenesis (GO:0003184)pulmonary valve morphogenesis (GO:0003184)regionalization (GO:0003002)regulation of DNA-templated transcription (GO:0006355)regulation of DNA-templated transcription (GO:0006355)regulation of multicellular organismal process (GO:0051239)regulation of transforming growth factor beta receptor signaling pathway (GO:0017015)response to cholesterol (GO:0070723)secondary palate development (GO:0062009)secondary palate development (GO:0062009)tau protein binding (GO:0048156)tau protein binding (GO:0048156)transcription regulator complex (GO:0005667)transcription regulator complex (GO:0005667)transforming growth factor beta receptor binding (GO:0005160)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor signaling pathway (GO:0007179)trophoblast cell migration (GO:0061450)type I transforming growth factor beta receptor binding (GO:0034713)ubiquitin protein ligase binding (GO:0031625)ureteric bud development (GO:0001657)zygotic specification of dorsal/ventral axis (GO:0007352)
Expression (TPM)
SMAD2 — as a Regulated Gene

TFs regulating SMAD2 0 TFs

Transcription factors with Perturb-seq knockdown data for SMAD2. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = SMAD2 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to SMAD2

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of SMAD2, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr18:47,748,983–47,749,659 181.6 kb Distal (>10kb) Multiome 523
chr18:47,888,213–47,888,747 42.3 kb Distal (>10kb) Multiome 112
chr18:47,899,238–47,900,034 31.3 kb Distal (>10kb) Multiome 78
chr18:47,901,678–47,902,259 28.9 kb Distal (>10kb) Multiome 164
chr18:47,926,327–47,927,065 4.3 kb Proximal (<10kb) Multiome 121
chr18:47,929,853–47,932,097 291 bp At TSS Multiome 1041
chr18:47,967,733–47,968,520 37.3 kb Distal (>10kb) Multiome 183
chr18:47,975,686–47,976,326 45.2 kb Distal (>10kb) Multiome 79
chr18:48,007,721–48,008,967 77.5 kb Distal (>10kb) Multiome HiCAR 431
chr18:48,161,014–48,162,366 230.9 kb Distal (>10kb) Multiome 453

Genome Browser

Genomic view of the SMAD2 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr18:47,738,983 – 48,172,366
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq