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 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 ...

' (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 Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology *Missile proliferation, the spread of lon ...

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 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 writt ...

by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member

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 ...

. 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

. 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 ''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'' ( ...

'' 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 Mothers Against Drunk Driving (MADD) is a non-profit organization in the United States, Canada ( MADD Canada) and Brazil that seeks to stop driving with any amount of alcohol in the bloodstream, support those affected by drunk driving, prevent un ...

, 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

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 Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. ...

, *

TGIF1 Homeobox protein TGIF1 is a protein that, in humans, is encoded by the ''TGIF1'' gene. Alternative splicing has been observed at this locus and eight variants, encoding four distinct isoforms, are described. Function The protein encoded by th ...

, *

Insulin receptor The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose h ...

, * LEF1, *

Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes r ...

, *

MEF2A Myocyte-specific enhancer factor 2A is a protein that in humans is encoded by the ''MEF2A'' gene. MEF2A is a transcription factor in the Mef2 family. In humans it is located on chromosome 15q26. Certain mutations in MEF2A cause an autosomal do ...

, *

PIAS3 E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene. Discovery IAS proteins were originally identified in studies that were aimed to decipher the Janus Kinase (JAK)/STAT signaling pathway. Originally, PIAS3 ...

, *

PIN1 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 is an enzyme that in humans is encoded by the ''PIN1'' gene. Pin 1, or peptidyl-prolyl cis/trans isomerase (PPIase), isomerizes only phospho-Serine/Threonine-Proline motifs. The enzyme b ...

, *

SKI protein The SKI protein is a nuclear Oncogene#Proto-oncogene, proto-oncogene that is associated with tumors at high cellular concentrations. SKI has been shown to interfere with normal cellular functioning by both directly impeding gene expression, expr ...

, *

SKIL Ski-like protein is a protein that in humans is encoded by the SKIL gene. Interactions SKIL interacts with SKI protein, Mothers against decapentaplegic homolog 3 and Mothers against decapentaplegic homolog 2. Protein Family SKIL belongs to t ...

, *

SMAD3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD (protein), SMAD family of proteins. It acts as a mediator of the signal ...

, *

SMURF2 E3 ubiquitin-protein ligase SMURF2 is an enzyme that in humans is encoded by the ''SMURF2'' gene which is located at chromosome 17q23.3-q24.1. Interactions SMURF2 has been shown to interact with: * Mothers against decapentaplegic homolog 1, ...

, *

SNW1 SNW domain-containing protein 1 is a protein that in humans is encoded by the ''SNW1'' gene. Function This gene, a member of the SNW gene family, encodes a coactivator that enhances transcription from some Pol II promoters. This coactivator ca ...

, *

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