ID:SMAD1_HUMAN DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 1; Short=MAD homolog 1; Short=Mothers against DPP homolog 1; AltName: Full=JV4-1; AltName: Full=Mad-related protein 1; AltName: Full=SMAD family member 1; Short=SMAD 1; Short=Smad1; Short=hSMAD1; AltName: Full=Transforming growth factor-beta-signaling protein 1; Short=BSP-1; FUNCTION: Transcriptional 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. SUBUNIT: Interacts with HGS, NANOG and ZCCHC12 (By similarity). May form 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. INTERACTION: P46937:YAP1; NbExp=3; IntAct=EBI-1567153, EBI-1044059; SUBCELLULAR LOCATION: Cytoplasm. 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. TISSUE SPECIFICITY: Ubiquitous. Highest expression seen in the heart and skeletal muscle. PTM: Phosphorylated on serine by BMP type 1 receptor kinase. PTM: Ubiquitinated 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. DISEASE: Defects in SMAD1 may be a cause of primary pulmonary hypertension (PPH1) [MIM:178600]. A rare 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 PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. SIMILARITY: Belongs to the dwarfin/SMAD family. SIMILARITY: Contains 1 MH1 (MAD homology 1) domain. SIMILARITY: Contains 1 MH2 (MAD homology 2) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15797
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0017151 DEAD/H-box RNA helicase binding GO:0019901 protein kinase binding GO:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0043565 sequence-specific DNA binding GO:0046872 metal ion binding GO:0046982 protein heterodimerization activity GO:0070410 co-SMAD binding GO:0070411 I-SMAD binding GO:0070878 primary miRNA binding
Biological Process: GO:0000165 MAPK cascade GO:0001657 ureteric bud development GO:0001710 mesodermal cell fate commitment GO:0002051 osteoblast fate commitment GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0006954 inflammatory response GO:0007165 signal transduction GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007183 SMAD protein complex assembly GO:0007276 gamete generation GO:0008285 negative regulation of cell proliferation GO:0009880 embryonic pattern specification GO:0010628 positive regulation of gene expression GO:0016579 protein deubiquitination GO:0030509 BMP signaling pathway GO:0030901 midbrain development GO:0030902 hindbrain development GO:0031053 primary miRNA processing GO:0042592 homeostatic process GO:0045669 positive regulation of osteoblast differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051216 cartilage development GO:0060038 cardiac muscle cell proliferation GO:0060348 bone development GO:0060395 SMAD protein signal transduction GO:0061036 positive regulation of cartilage development GO:0071407 cellular response to organic cyclic compound GO:0071773 cellular response to BMP stimulus GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1903672 positive regulation of sprouting angiogenesis
Protein Q15797 (Reactome details) participates in the following event(s):
R-HSA-201422 Phospho-R-Smad1/5/8 forms a complex with Co-Smad R-HSA-202626 I-Smad competes with Co-Smad for R-Smad1/5/8 R-HSA-201453 Phospho-R-Smad1/5/8 dissociates from the receptor complex R-HSA-201648 An anchoring protein, Endofin, recruits R-Smad1/5/8 R-HSA-8877941 RUNX2 binds SMAD1 in the nucleus R-HSA-201472 The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus R-HSA-201476 Activated type I receptor phosphorylates R-Smad1/5/8 directly R-HSA-6781764 USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1 R-HSA-8878013 RUNX2 and SMAD1 complex binds the SMAD6 gene promoter R-HSA-201423 SKI complexes with the Smad complex, suppressing BMP2 signalling R-HSA-201451 Signaling by BMP R-HSA-8941326 RUNX2 regulates bone development R-HSA-9006936 Signaling by TGF-beta family members R-HSA-5689880 Ub-specific processing proteases R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-162582 Signal Transduction R-HSA-5688426 Deubiquitination R-HSA-212436 Generic Transcription Pathway R-HSA-597592 Post-translational protein modification R-HSA-73857 RNA Polymerase II Transcription R-HSA-392499 Metabolism of proteins R-HSA-74160 Gene expression (Transcription)
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
