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MGP001854

UniProt Annotations

Entry Information
Gene NameSMAD family member 1
Protein EntrySMAD1_HUMAN
UniProt IDQ15797
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q15797-1; Sequence=Displayed; Name=2; IsoId=Q15797-2; Sequence=VSP_057163, VSP_057164, VSP_057165, VSP_057166; Note=No experimental confirmation available.;
DiseaseNote=SMAD1 variants may be associated with susceptibility to pulmonary hypertension, a disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
DomainThe MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit. {ECO:0000269|PubMed:11779505}.
FunctionTranscriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. {ECO:0000269|PubMed:12097147}.
InteractionP10275:AR; NbExp=6; IntAct=EBI-1567153, EBI-608057; P49841:GSK3B; NbExp=2; IntAct=EBI-1567153, EBI-373586; Q13485:SMAD4; NbExp=4; IntAct=EBI-1567153, EBI-347263; O43541:SMAD6; NbExp=4; IntAct=EBI-1567153, EBI-976374; Q9HCE7:SMURF1; NbExp=2; IntAct=EBI-1567153, EBI-976466; Q9HCE7-2:SMURF1; NbExp=2; IntAct=EBI-1567153, EBI-9845742; P15374:UCHL3; NbExp=2; IntAct=EBI-1567153, EBI-954554; P46937:YAP1; NbExp=3; IntAct=EBI-1567153, EBI-1044059;
PtmPhosphorylation of the C-terminal SVS motif by BMP type 1 receptor kinase activates SMAD1 by promoting dissociation from the receptor and trimerization with SMAD4. {ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9136927}.
PtmUbiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading to its degradation. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes. {ECO:0000269|PubMed:21947082}.
SimilarityBelongs to the dwarfin/SMAD family. {ECO:0000305}.
SimilarityContains 1 MH1 (MAD homology 1) domain. {ECO:0000255|PROSITE-ProRule:PRU00438}.
SimilarityContains 1 MH2 (MAD homology 2) domain. {ECO:0000255|PROSITE-ProRule:PRU00439}.
Subcellular LocationCytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4. Co-localizes with LEMD3 at the nucleus inner membrane.
SubunitFound in a complex with SMAD4 and YY1. Interacts with HGS, NANOG and ZCCHC12 (By similarity). Upon C-terminus phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial reduction of receptor-mediated phosphorylation. Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Found in a macromolecular complex with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. {ECO:0000250, ECO:0000269|PubMed:10660046, ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:14630787, ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:17292623, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:24554596}.
Tissue SpecificityUbiquitous. Highest expression seen in the heart and skeletal muscle.
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