SMAD6
Identifiers
Aliases	SMAD6, AOVD2, HsT17432, MADH6, MADH7, SMAD family member 6
External IDs	OMIM: 602931 MGI: 1336883 HomoloGene: 4079 GeneCards: SMAD6
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q22.31 Start 66,702,236 bp[1] End 66,782,849 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 C Start 63,860,358 bp[2] End 63,929,341 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung glomerulus metanephric glomerulus lower lobe of lung upper lobe of lung upper lobe of left lung visceral pleura right lobe of thyroid gland retinal pigment epithelium right coronary artery Top expressed in right lung right lung lobe molar atrium epithelium of stomach external carotid artery left lung seminiferous tubule endocardial cushion internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding R-SMAD binding type I transforming growth factor beta receptor binding co-SMAD binding I-SMAD binding DNA-binding transcription factor activity chromatin binding type I activin receptor binding metal ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding identical protein binding ubiquitin protein ligase binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm transcription regulator complex intracellular anatomical structure nucleus Golgi apparatus cytosol nuclear body protein-containing complex Biological process ureteric bud development heart valve development regulation of transcription, DNA-templated ventricular septum development zygotic specification of dorsal/ventral axis negative regulation of SMAD protein complex assembly response to laminar fluid shear stress negative regulation of apoptotic process negative regulation of transforming growth factor beta receptor signaling pathway coronary vasculature development BMP signaling pathway transcription, DNA-templated negative regulation of pathway-restricted SMAD protein phosphorylation response to estrogen negative regulation of BMP signaling pathway aorta development cell-substrate adhesion immune response transforming growth factor beta receptor signaling pathway fat cell differentiation negative regulation of cell population proliferation positive regulation of pri-miRNA transcription by RNA polymerase II outflow tract septum morphogenesis mitral valve morphogenesis pulmonary valve morphogenesis negative regulation of ossification aortic valve morphogenesis negative regulation of osteoblast differentiation response to lipopolysaccharide Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4091 17130 Ensembl ENSG00000137834 ENSMUSG00000036867 UniProt O43541 O35182 RefSeq (mRNA) NM_001142861 NM_005585 NM_008542 RefSeq (protein) NP_005576 NP_032568 Location (UCSC) Chr 15: 66.7 – 66.78 Mb Chr 9: 63.86 – 63.93 Mb PubMed search [3] [4]
Wikidata
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SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.^[5]

SMAD6 is a protein that, as its name describes, is a homolog of the Drosophila gene "mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members SMAD6 is involved in cell signalling. It acts as a regulator of TGFβ family (such as bone morphogenetic proteins) activity by competing with SMAD4 and preventing the transcription of SMAD4's gene products. There are two known isoforms of this protein.

Nomenclature

The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic in the embryo. The phrase "Mothers against" was added as a humorous take-off on organizations opposing various issues e.g., Mothers Against Drunk Driving, or MADD; and based on a tradition of such unusual naming within the gene research community.^[6]

Disease associations

Heterozygous, damaging mutations in SMAD6 are the most frequent genetic cause of non-syndromic craniosynostosis identified to date.^[7]

Interactions

Mothers against decapentaplegic homolog 6 has been shown to interact with:

• HOXC8,^[8]
• MAP3K7,^[9][10]
• Mothers against decapentaplegic homolog 7,^[11]
• PIAS4,^[12] and
• STRAP.^[13]