Mothers against decapentaplegic homolog 2, also known as SMAD family member 2 or SMAD2, 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 ''SMAD2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products 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' (Mad) and the '' C. elegans'' gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.

Function

SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation,

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

, where it binds to target promoters and forms a transcription

repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...

complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants encoding the same protein have been observed. Like other SMADs, SMAD2 plays a role in the transmission of extracellular signals from ligands of the Transforming Growth Factor beta (TGFβ) superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular receptors triggers phosphorylation of SMAD2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its extreme C-terminus. Phosphorylated SMAD2 is then able to form a complex with SMAD4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

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 ''

'' 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). The nomenclature for this protein is 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

Interactions

Mothers against decapentaplegic homolog 2 has been shown to interact with: * ANAPC10, * DAB2, *

EP300 Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone ace ...

, *

FOXH1 Forkhead box protein H1 is a protein that in humans is encoded by the ''FOXH1'' gene. Function FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element ...

, * HDAC1, * TGIF1, * Insulin receptor, * LEF1, * Myc, * MEF2A, * PIAS3, * PIN1, * SKI protein, * SKIL, * SMAD3, * SMURF2, * SNW1, *

STRAP A strap, sometimes also called strop, is an elongated flap or ribbon, usually of leather or other flexible materials. Thin straps are used as part of clothing or baggage, or bedding such as a sleeping bag. See for example spaghetti strap, s ...

WWTR1 WW domain-containing transcription regulator protein 1 (WWTR1), also known as Coactivator (genetics), Transcriptional coactivator with PDZ-binding motif (TAZ), is a protein that in humans is encoded by the ''WWTR1'' gene. WWTR1 acts as a Transcri ...

Function

Nomenclature

Interactions

References

Further reading