SMAD family member 6, also known as SMAD6, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''SMAD6''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
SMAD6 is a protein that, as its name describes, is a homolog of the
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
gene "
mothers against decapentaplegic". It belongs to the
SMAD family of proteins, which belong to the
TGFβ
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sig ...
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
SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, ...
and preventing the transcription of
SMAD4
SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, ...
'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
Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly ''Drosophila melanogaster'' and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early ' ...
'' 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
Mothers Against Drunk Driving (MADD) is a non-profit organization in the United States, Canada and Brazil that seeks to stop drunk driving, support those affected by drunk driving, prevent underage drinking, and strive for stricter impaired drivi ...
, or MADD; and based on a tradition of such unusual naming within the gene research community.
Disease associations
Heterozygous, damaging mutations in SMAD6 are the most frequent genetic cause of non-syndromic
craniosynostosis identified to date.
Interactions
Mothers against decapentaplegic homolog 6 has been shown to
interact with:
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HOXC8,
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MAP3K7
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the ''MAP3K7'' gene.
Structure
TAK1 is an evolutionarily conserved kinase in the MAP3 K family and clusters with the tyro ...
,
*
Mothers against decapentaplegic homolog 7
Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the ''SMAD7'' gene.
SMAD7 is a protein that, as its name describes, is a homolog of the Drosophila gene: "Mothers against decapentaplegic". It belongs to ...
,
*
PIAS4
E3 SUMO-protein ligase PIAS4 is one of several protein inhibitor of activated STAT (PIAS) proteins. It is also known as protein inhibitor of activated STAT protein gamma (PIASg or PIASy), and is an enzyme that in humans is encoded by the ''PIAS4' ...
,
and
*
STRAP.
References
Further reading
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Transcription factors
Developmental genes and proteins
MH1 domain
MH2 domain
Human proteins
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