InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMAD6

Summary

InnateDB Protein

IDBP-596149.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SMAD6

Protein Name

SMAD family member 6

Synonyms

AOVD2; HsT17432; MADH6; MADH7;

Species

Homo sapiens

Ensembl Protein

ENSP00000452955

InnateDB Gene

IDBG-18304 (SMAD6)

Protein Structure

UniProt Annotation

Function

Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions. {ECO:0000269PubMed:16491121, ECO:0000269PubMed:16951688, ECO:0000269PubMed:9436979}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:16491121}.

Disease Associations

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, stenosis 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. {ECO:0000269PubMed:22275001}. Note=The disease is caused by mutations affecting the gene represented in this entry. 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). {ECO:0000269PubMed:22275001}.

Tissue Specificity

Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased heart tissue.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	69 [view]
Protein-Protein	68 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0030617	transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity
GO:0031625	ubiquitin protein ligase binding
GO:0034713	type I transforming growth factor beta receptor binding
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding
GO:0070410	co-SMAD binding
GO:0070411	I-SMAD binding
GO:0070412	R-SMAD binding
GO:0070698	type I activin receptor binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006955	immune response
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007352	zygotic specification of dorsal/ventral axis
GO:0008285	negative regulation of cell proliferation
GO:0010991	negative regulation of SMAD protein complex assembly
GO:0030509	BMP signaling pathway
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030514	negative regulation of BMP signaling pathway
GO:0031589	cell-substrate adhesion
GO:0034616	response to laminar fluid shear stress
GO:0035556	intracellular signal transduction
GO:0043066	negative regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045444	fat cell differentiation
GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation