Human Gene SMAD6 (ENST00000288840.10) from GENCODE V41
Description: Homo sapiens SMAD family member 6 (SMAD6), transcript variant 3, non-coding RNA. (from RefSeq NR_027654) RefSeq Summary (NM_005585): The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]. Gencode Transcript: ENST00000288840.10 Gencode Gene: ENSG00000137834.15 Transcript (Including UTRs) Position: hg38 chr15:66,702,236-66,782,849 Size: 80,614 Total Exon Count: 4 Strand: + Coding Region Position: hg38 chr15:66,703,259-66,781,535 Size: 78,277 Coding Exon Count: 4
ID:SMAD6_HUMAN DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 6; Short=MAD homolog 6; Short=Mothers against DPP homolog 6; AltName: Full=SMAD family member 6; Short=SMAD 6; Short=Smad6; Short=hSMAD6; FUNCTION: Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit selectively BMP (bone morphogenetic proteins) signaling by competing with the co-SMAD SMAD4 for receptor-activated SMAD1. SMAD6 is an inhibitory SMAD (I-SMAD) or antagonistic SMAD. Binds to regulatory elements in target promoter regions. SUBUNIT: Interacts with NEDD4L (By similarity). Interacts with WWP1 (By similarity). Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, SMAD1, HOXC8 and HOXC9. Interacts with STAMBP and PRKX. INTERACTION: P51817:PRKX; NbExp=5; IntAct=EBI-976374, EBI-4302903; Q13950:RUNX2; NbExp=3; IntAct=EBI-976374, EBI-976402; O95630:STAMBP; NbExp=2; IntAct=EBI-4324970, EBI-396676; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased heart tissue. PTM: Phosphorylated by BMP type 1 receptor kinase and by PRKX. PTM: Ubiquitinated by WWP1 (By similarity). DISEASE: Defects in SMAD6 are the cause of aortic valve disease 2 (AOVD2) [MIM:614823]. A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. Note=SMAD6 variants may contribute to increased risk of congenital cardiovascular malformations (CVM). CVM is a major cause of mortality and morbidity in childhood. In most sporadic cases that cannot be attributed to particular malformation syndromes or teratogenic exposures, there remains a substantial excess familial risk, indicating a significant genetic contribution to disease susceptibility (PubMed:22275001). 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 O43541
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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.