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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SMAD9'' gene. SMAD9, 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 species ...

gene: "

Mothers against decapentaplegic Mothers against decapentaplegic is a protein from the SMAD family that was discovered in ''Drosophila''. During ''Drosophila'' research, it was found that a mutation in the gene in the mother repressed the gene decapentaplegic in the embryo. The ...

". 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 sign ...

superfamily of modulators. Like many other TGFβ family members, SMAD9 is involved in

cell signalling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

. When a

bone morphogenetic protein Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of piv ...

binds to a receptor ( BMP type 1 receptor kinase) it causes SMAD9 to interact with

SMAD anchor for receptor activation Zinc finger FYVE domain-containing protein 9 or SARA (SMAD anchor for receptor activation) is a protein that in humans is encoded by the ''ZFYVE9'' gene. SARA contains a double zinc finger (FYVE domain). SARA is an anchoring protein involved in ...

(SARA).The binding of ligands causes the

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

of the SMAD9 protein and the dissociation from SARA and the association 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, ...

. It is subsequently transferred to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

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 of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

. 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 gen ...

) 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 or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

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 ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

'' 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 since mothers often form 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."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