SMAD1: A Key Mediator of BMP Signaling in Development and Disease
Comprehensive genomic and proteomic overview of SMAD1, a central signal transducer in the bone morphogenetic protein (BMP) pathway.
Gene Information Card
| Symbol | SMAD1 |
|---|---|
| Full Name | SMAD family member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 4086 ncbi.nlm.nih.gov/gene/4086 |
| Ensembl ID | ENSG00000170365 |
| UniProt ID | Q15797 |
| OMIM ID | 601595 |
| HGNC ID | 6767 |
| Aliases | MADH1, MADR1, JV4-1, BSP-1 |
Description
SMAD1 (SMAD family member 1) is a signal transducer and transcription factor that mediates the effects of bone morphogenetic proteins (BMPs). Upon BMP receptor activation, SMAD1 is phosphorylated, forms a complex with SMAD4, and translocates to the nucleus to regulate target gene expression. It is essential for bone development, cell differentiation, and homeostasis. Dysregulation of SMAD1 is implicated in fibrodysplasia ossificans progressiva, pulmonary arterial hypertension, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fibrodysplasia Ossificans Progressiva (FOP) | Gain-of-function mutations in ACVR1 lead to constitutive BMP signaling and SMAD1 hyperactivation, causing heterotopic ossification. | OMIM #135100 |
| Pulmonary Arterial Hypertension (PAH) | Dysregulated BMPR2 signaling reduces SMAD1 phosphorylation, contributing to vascular remodeling. | ClinVar; PMID: 19555857 |
| Colorectal Cancer | SMAD1 overexpression and altered BMP signaling promote tumor progression and metastasis. | COSMIC; PMID: 23431147 |
| Prostate Cancer | SMAD1 acts as a tumor suppressor; loss of expression correlates with poor prognosis. | NCBI Gene; PMID: 20628055 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 15.2 | Medium |
| Kidney | 12.8 | Medium |
| Liver | 8.5 | Low |
| Heart | 6.3 | Low |
| Brain | 4.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 18.5 | High expression |
| HEK293 (Embryonic kidney) | 14.2 | Moderate expression |
| HepG2 (Liver carcinoma) | 9.7 | Low expression |
| MCF7 (Breast carcinoma) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.617G>A (p.Arg206His) | Missense | <0.01% | Reported in FOP; enhances BMP signaling |
| c.1067C>T (p.Pro356Leu) | Missense | <0.01% | Unknown significance; observed in cancer |
| c.1240_1242del (p.Lys414del) | Deletion | <0.01% | Loss of function; associated with PAH |
Mutation functional classification
Loss of Function (LOF)
Deletions or nonsense mutations that impair SMAD1 phosphorylation or nuclear translocation reduce BMP signaling, linked to PAH and vascular defects.
Gain of Function (GOF)
Missense mutations (e.g., Arg206His) enhance SMAD1 activation, leading to excessive BMP signaling and heterotopic ossification in FOP.
Dominant Negative (DN)
Truncated SMAD1 variants that retain DNA binding but lack transactivation domain can interfere with wild-type SMAD1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• TGF-beta signaling pathway (KEGG: hsa04350)
• Signaling by BMP (Reactome: R-HSA-201451)
Protein Summary
SMAD1 is a 465-amino-acid protein (52 kDa) containing an N-terminal MH1 domain for DNA binding, a linker region, and a C-terminal MH2 domain for receptor interaction and oligomerization. It is phosphorylated at Ser463/465 by BMP type I receptors. The protein shuttles between cytoplasm and nucleus, acting as a transcriptional co-regulator. Post-translational modifications include phosphorylation, ubiquitination, and sumoylation, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMAD1 Knockout HEK293 Cell Line | EDJ-KQ399 | Human | 4086 | Details Get a Quote |
| SMAD1 Knockout A-549 Cell Line | EDJ-KQ18634 | Human | 4086 | Details Get a Quote |
| SMAD1 Knockout HCT 116 Cell Line | EDJ-KQ18635 | Human | 4086 | Details Get a Quote |
| SMAD1 Knockout HeLa Cell Line | EDJ-KQ18636 | Human | 4086 | Details Get a Quote |
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