SMAD6
SMAD family member 6 | HsT17432, MADH6, MADH7

The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

Member of: DE-3 Developmental clusters: GC6
Biological processes 78 terms
BMP signaling pathway (GO:0030509)BMP signaling pathway (GO:0030509)I-SMAD binding (GO:0070411)I-SMAD binding (GO:0070411)I-SMAD binding (GO:0070411)R-SMAD binding (GO:0070412)SMAD protein signal transduction (GO:0060395)activin receptor binding (GO:0070697)anatomical structure morphogenesis (GO:0009653)aortic valve morphogenesis (GO:0003180)cell differentiation (GO:0030154)cell-substrate adhesion (GO:0031589)cellular response to growth factor stimulus (GO:0071363)chromatin (GO:0000785)chromatin binding (GO:0003682)ciliary basal body (GO:0036064)co-SMAD binding (GO:0070410)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)fat cell differentiation (GO:0045444)heteromeric SMAD protein complex (GO:0071144)identical protein binding (GO:0042802)immune response (GO:0006955)mitral valve morphogenesis (GO:0003183)mitral valve morphogenesis (GO:0003183)negative regulation of BMP signaling pathway (GO:0030514)negative regulation of BMP signaling pathway (GO:0030514)negative regulation of BMP signaling pathway (GO:0030514)negative regulation of MyD88-dependent toll-like receptor signaling pathway (GO:0034125)negative regulation of SMAD protein signal transduction (GO:0060392)negative regulation of SMAD protein signal transduction (GO:0060392)negative regulation of SMAD protein signal transduction (GO:0060392)negative regulation of activin receptor signaling pathway (GO:0032926)negative regulation of activin receptor signaling pathway (GO:0032926)negative regulation of apoptotic process (GO:0043066)negative regulation of cell differentiation (GO:0045596)negative regulation of cell population proliferation (GO:0008285)negative regulation of ossification (GO:0030279)negative regulation of ossification (GO:0030279)negative regulation of osteoblast differentiation (GO:0045668)negative regulation of osteoblast differentiation (GO:0045668)negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512)negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512)negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512)nuclear body (GO:0016604)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)outflow tract septum morphogenesis (GO:0003148)outflow tract septum morphogenesis (GO:0003148)positive regulation of miRNA transcription (GO:1902895)proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)protein binding (GO:0005515)protein sequestering activity (GO:0140311)protein-containing complex (GO:0032991)pulmonary valve morphogenesis (GO:0003184)pulmonary valve morphogenesis (GO:0003184)regulation of DNA-templated transcription (GO:0006355)regulation of transcription by RNA polymerase II (GO:0006357)response to estrogen (GO:0043627)response to laminar fluid shear stress (GO:0034616)response to lipopolysaccharide (GO:0032496)transcription cis-regulatory region binding (GO:0000976)transcription regulator complex (GO:0005667)transcription regulator inhibitor activity (GO:0140416)transcription regulator inhibitor activity (GO:0140416)transcription regulator inhibitor activity (GO:0140416)transcription regulator inhibitor activity (GO:0140416)transforming growth factor beta receptor superfamily signaling pathway (GO:0141091)type I activin receptor binding (GO:0070698)type I transforming growth factor beta receptor binding (GO:0034713)type I transforming growth factor beta receptor binding (GO:0034713)ubiquitin protein ligase binding (GO:0031625)ubiquitin-like ligase-substrate adaptor activity (GO:1990756)ureteric bud development (GO:0001657)zygotic specification of dorsal/ventral axis (GO:0007352)
Expression (TPM)
SMAD6 — as a Regulated Gene

TFs regulating SMAD6 0 TFs

Transcription factors with Perturb-seq knockdown data for SMAD6. 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 = SMAD6 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 SMAD6

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of SMAD6, 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
chr15:66,472,216–66,473,164 229.7 kb Distal (>10kb) Multiome 208
chr15:66,497,104–66,498,247 204.5 kb Distal (>10kb) Multiome 1044
chr15:66,504,543–66,505,655 197.1 kb Distal (>10kb) Multiome 940
chr15:66,567,056–66,567,492 135.0 kb Distal (>10kb) Multiome 294
chr15:66,592,463–66,593,143 109.5 kb Distal (>10kb) Multiome HiCAR 154
chr15:66,621,672–66,622,446 80.0 kb Distal (>10kb) Multiome 271
chr15:66,630,856–66,631,340 71.1 kb Distal (>10kb) Multiome 284
chr15:66,670,796–66,671,740 31.0 kb Distal (>10kb) Multiome 241
chr15:66,673,331–66,673,903 28.5 kb Distal (>10kb) Multiome 192
chr15:66,679,362–66,680,264 22.4 kb Distal (>10kb) Multiome 541
chr15:66,691,568–66,692,527 10.1 kb Distal (>10kb) Multiome 33
chr15:66,698,421–66,699,404 3.1 kb Proximal (<10kb) Multiome 321
chr15:66,700,619–66,702,650 1.1 kb Proximal (<10kb) Multiome 844
chr15:66,707,348–66,707,765 5.1 kb Proximal (<10kb) 182
chr15:66,773,918–66,774,633 72.2 kb Distal (>10kb) Multiome 524
chr15:66,842,072–66,842,664 140.4 kb Distal (>10kb) Multiome 519
chr15:66,842,765–66,843,830 141.1 kb Distal (>10kb) Multiome 413
chr15:66,923,439–66,924,007 221.5 kb Distal (>10kb) Multiome 191
chr15:66,927,757–66,928,460 226.0 kb Distal (>10kb) Multiome 77

Genome Browser

Genomic view of the SMAD6 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.

chr15:66,462,216 – 66,938,460
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq