SMAD5 Transcription Factor
SMAD family member 5 | Dwfc, JV5-1, MADH5

The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Member of: DE-6
Biological processes 67 terms
BMP signaling pathway (GO:0030509)BMP signaling pathway (GO:0030509)BMP signaling pathway (GO:0030509)BMP signaling pathway (GO:0030509)DEAD/H-box RNA helicase binding (GO:0017151)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 repressor activity, RNA polymerase II-specific (GO:0001227)I-SMAD binding (GO:0070411)Mullerian duct regression (GO:0001880)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 cis-regulatory region sequence-specific DNA binding (GO:0000978)RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977)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)anatomical structure morphogenesis (GO:0009653)anti-Mullerian hormone receptor signaling pathway (GO:1990262)cardiac conduction system development (GO:0003161)cell differentiation (GO:0030154)cell differentiation (GO:0030154)cellular response to growth factor stimulus (GO:0071363)chromatin (GO:0000785)chromatin (GO:0000785)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)developmental process (GO:0032502)embryonic pattern specification (GO:0009880)heteromeric SMAD protein complex (GO:0071144)intracellular iron ion homeostasis (GO:0006879)mitochondrion (GO:0005739)negative regulation of Fas signaling pathway (GO:1902045)negative regulation of apoptotic process (GO:0043066)negative regulation of gene expression (GO:0010629)negative regulation of transcription by RNA polymerase II (GO:0000122)nucleoplasm (GO:0005654)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)ossification (GO:0001503)osteoblast differentiation (GO:0001649)positive regulation of DNA-templated transcription (GO:0045893)positive regulation of osteoblast differentiation (GO:0045669)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)protein binding (GO:0005515)protein-containing complex (GO:0032991)regulation of DNA-templated transcription (GO:0006355)regulation of transcription by RNA polymerase II (GO:0006357)sequence-specific double-stranded DNA binding (GO:1990837)signal transduction (GO:0007165)stem cell differentiation (GO:0048863)stem cell differentiation (GO:0048863)transcription regulator complex (GO:0005667)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor signaling pathway (GO:0007179)transforming growth factor beta receptor superfamily signaling pathway (GO:0141091)ubiquitin protein ligase binding (GO:0031625)ureteric bud development (GO:0001657)
Expression (TPM)
SMAD5 — as a Regulator

Modules regulated by SMAD5

Modules significantly affected by knockdown. ↑ Up = module upregulated upon KD; ↓ Down = module downregulated upon KD.

Evidence: Direction:
Perturbation + Binding
Perturbation only
Binding only
Cluster Dir NES padj Bind OR padj (bind)
Evidence: Direction:
Perturbation + Binding
Perturbation only
Binding only
Module Dir NES #gRNA padj Bind OR padj (bind)
Evidence: Direction: Max shown:
Perturbation + Binding
Perturbation only
Binding only
Submodule Module Dir NES #gRNA Bind OR padj (bind)

Genes regulated by SMAD5

Genes likely regulated by SMAD5 through linked binding evidence in open chromatin. The chart ranks TF-linked genes by their mean Perturb-seq response to SMAD5 knockdown, with negative coefficients indicating downregulation and positive coefficients indicating upregulation upon knockdown.

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Regulatory Elements bound by the TF

Open chromatin elements (ATAC-seq) where SMAD5 has ChIP-seq or motif footprint binding evidence and which are linked to at least one target gene region.

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SMAD5 — as a Regulated Gene

TFs regulating SMAD5 0 TFs

Transcription factors with Perturb-seq knockdown data for SMAD5. 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 = SMAD5 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 SMAD5

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of SMAD5, 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
chr5:135,834,157–135,835,549 298.1 kb Distal (>10kb) Multiome 472
chr5:135,859,255–135,860,157 273.1 kb Distal (>10kb) Multiome 15
chr5:135,877,361–135,878,257 255.1 kb Distal (>10kb) Multiome 83
chr5:135,929,925–135,930,988 202.5 kb Distal (>10kb) Multiome 487
chr5:135,978,027–135,978,664 154.3 kb Distal (>10kb) Multiome 32
chr5:136,028,641–136,029,690 103.8 kb Distal (>10kb) Multiome 586
chr5:136,132,529–136,134,031 40 bp At TSS Multiome 958
chr5:136,191,541–136,193,668 60.2 kb Distal (>10kb) Multiome 393
chr5:136,381,866–136,382,474 249.4 kb Distal (>10kb) Multiome 101

Genome Browser

Genomic view of the SMAD5 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.

chr5:135,824,157 – 136,392,474
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq