Free for academic non-profit institutions. Other users need a Commercial license
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 signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
SMAD1 (SMAD Family Member 1) is a Protein Coding gene. Diseases associated with SMAD1 include Buschke-Ollendorff Syndrome and Melorheostosis. Among its related pathways are Transcriptional misregulation in cancer and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein kinase binding. An important paralog of this gene is SMAD5.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 12270938 |
GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | ISM | 19274049 |
GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IDA | 12270938 |
GO:0003677 | DNA binding | IEA | -- |
GO:0003700 | DNA-binding transcription factor activity | IDA | 9389648 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000790 | nuclear chromatin | ISA | -- |
GO:0005634 | nucleus | NAS,TAS | 19018011 |
GO:0005637 | nuclear inner membrane | IDA | 15647271 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005667 | transcription factor complex | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Signaling by BMP |
.33
|
|
2 | nNOS Signaling in Skeletal Muscle |
BMP Pathway
.44
|
TOB in Osteoblast Signaling
.01
|
3 | Human Embryonic Stem Cell Pluripotency |
Factors Promoting Cardiogenesis in Vertebrates
.50
|
Human Embryonic Stem Cell Pluripotency
.50
|
4 | TGF-Beta Pathway |
TGF-Beta Pathway
.60
|
JAK-STAT Pathway
.57
|
5 | Deubiquitination |
.74
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | IEA | -- |
GO:0001657 | ureteric bud development | IEA | -- |
GO:0001710 | mesodermal cell fate commitment | IEA | -- |
GO:0002051 | osteoblast fate commitment | IEA | -- |
GO:0006355 | regulation of transcription, DNA-templated | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Pirfenidone | Approved, Investigational | Pharma | TGF-β production inhibitor, Antifibrotic agent; regulates cytokine levels in vivo | 86 | ||
LDN193189 Hydrochloride | Pharma | ALK inhibitor,potent and selective | 0 | |||
LY364947 | Pharma | 0 | ||||
RepSox | Pharma | ALK5 inhibitor,potent and selective, Potent and selective inhibitor of TGF-betaRI | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
LDN193189 Hydrochloride | ALK inhibitor,potent and selective | 1062368-62-0 |
LY364947 | 396129-53-6 | |
Pirfenidone | TGF-β production inhibitor | 53179-13-8 |
RepSox | ALK5 inhibitor,potent and selective | 446859-33-2 |
ExUns: | 1 | ^ | 2a | · | 2b | ^ | 3a | · | 3b | ^ | 4a | · | 4b | ^ | 5a | · | 5b | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | · | 8c | · | 8d | · | 8e | · | 8f | · | 8g | ^ | 9 | ^ | 10 | ^ | 11a | · | 11b | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP9: | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP10: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP12: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MADH1 31 |
|
OneToOne | |
SMAD1 30 |
|
||||
Platypus (Ornithorhynchus anatinus) |
Mammalia | SMAD1 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | SMAD1 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | SMAD1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | SMAD1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Smad1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Smad1 30 |
|
||
Chicken (Gallus gallus) |
Aves | SMAD1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | SMAD1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | smad1 30 |
|
||
Str.8919 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.87 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | smad1 30 31 |
|
ManyToMany | |
Fruit Fly (Drosophila melanogaster) |
Insecta | Mad 30 31 |
|
ManyToMany | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP008551 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | sma-2 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.8058 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 04 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs587777018 | Uncertain Significance: Variant of unknown significance; Primary pulmonary hypertension. - | 145,514,621(+) | T/Cp.Val3Ala | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv128e180 | CNV | loss | 20482838 |
dgv900n67 | CNV | loss | 20364138 |
dgv9299n54 | CNV | gain | 21841781 |
dgv9300n54 | CNV | loss | 21841781 |
dgv981e199 | CNV | deletion | 23128226 |
esv1000240 | CNV | deletion | 20482838 |
esv1540098 | CNV | deletion | 17803354 |
esv2662386 | CNV | deletion | 23128226 |
esv2728491 | CNV | deletion | 23290073 |
esv2728492 | CNV | deletion | 23290073 |
esv28792 | CNV | loss | 19812545 |
esv3298273 | CNV | deletion | 24192839 |
esv3564752 | CNV | deletion | 23714750 |
esv3602561 | CNV | loss | 21293372 |
esv3602562 | CNV | loss | 21293372 |
nsv1074222 | CNV | deletion | 25765185 |
nsv1126699 | CNV | deletion | 24896259 |
nsv511241 | CNV | loss | 21212237 |
nsv513171 | CNV | loss | 21212237 |
nsv595621 | CNV | loss | 21841781 |
nsv595623 | CNV | gain+loss | 21841781 |
nsv595625 | CNV | gain | 21841781 |
nsv822763 | CNV | loss | 20364138 |
Disorder | Aliases | PubMed IDs |
---|---|---|
buschke-ollendorff syndrome |
|
|
melorheostosis |
|
|
osteopoikilosis |
|
|
pulmonary hypertension |
|
|
fibrodysplasia ossificans progressiva |
|
|