Mothers against decapentaplegic homolog 9 also known as SMAD9, SMAD8, and MADH6 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SMAD9'' gene. SMAD9, as its name describes, is a homolog of the

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

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, SMAD9 is involved in

cell signalling In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

. When a

bone morphogenetic protein Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Professor Marshall Urist and Professor Hari Reddi discovered their ability to induce the formation of bone and cartilage, BMPs are now ...

binds to a receptor ( BMP type 1 receptor kinase) it causes SMAD9 to interact with SMAD anchor for receptor activation (SARA).The binding of ligands causes the

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

of the SMAD9 protein and the dissociation from SARA and the association with SMAD4. It is subsequently transferred to the nucleus where it forms complexes with other proteins and acts as a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

. SMAD9 is a receptor regulated SMAD (

R-SMAD R-SMADs are receptor-regulated SMADs. SMADs are transcription factors that transduce extracellular TGF-β superfamily ligand signaling from cell membrane bound TGF-β receptors into the nucleus where they activate transcription TGF-β target ge ...

) and is activated by bone morphogenetic protein type 1 receptor kinase. There are two

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

of the protein. Confusingly, it is also sometimes referred to as SMAD8 in the literature.

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 ...

'', in the embryo. The phrase "Mothers against" was added since mothers often form 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."Sonic Hedgehog, DICER, and the Problem With Naming Genes"
Sep 26, 2014, Michael White. psmag.com

References

Developmental genes and proteins MH1 domain MH2 domain R-SMAD Transcription factors Human proteins {{cell-biology-stub