Function
Acts as an inhibitory regulator of signaling mediated by the TGF-beta superfamily, with strong selectivity toward BMP-dependent pathways. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear translocation and NF-kappa-B-mediated expression of pro-inflammatory genes. Blocks the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding.
Biological Context
Subcellular Location: Nucleus; Cytoplasm
Tissue Specificity: Expressed in the brain, heart, ovary, peripheral blood leukocytes, small intestine, spleen, thymus, bone marrow, fetal liver and lymph nodes
Disease Association: Aortic valve disease 2 (AOVD2) : 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. [The disease is caused by variants 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 ] | Craniosynostosis 7 (CRS7) : A form of craniosynostosis, a primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. [Disease susceptibility is associated with variants affecting the gene represented in this entry. Rare heterozygous SMAD6 variants have been reported to be strongly associated with non-syndromic midline craniosynostosis, confering a very high risk for disease development in the presence of a common risk allele (rs1884302) near the BMP2 locus. The modifier role of rs1884302 SNP on craniosynostosis development associated with SMAD6 variants has not been confirmed in further studies ] | Radioulnar synostosis, non-syndromic (RUS) : An autosomal dominant disease characterized by proximal fusion of the radius and ulna resulting in extremely limited pronation and supination of the forearm. There are two disease forms. Radioulnar synostosis type 1 is characterized by a proximal fusion between the radius and ulna, and the radial head is absent. Radioulnar synostosis type 2 is characterized by a fusion just distal to the proximal radial epiphysis, and congenital dislocation of the radial head. In radioulnar synostosis type 2 there is also a restriction of extension at the elbow. [Disease susceptibility is associated with variants affecting the gene represented in this entry]
Product Specifications
Recombinant Human Mothers against decapentaplegic homolog 6 (SMAD6) is a recombinant protein from Homo sapiens (Human), expressed in E.coli, covering amino acids 1-496aa, with N-terminal 10xHis-tagged and C-terminal Myc-tagged tag, molecular weight 60.9kDa, purity Greater than 85% as determined by SDS-PAGE.. Suitable for ELISA and Western Blot applications.
