Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the ''SMAD2'' gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the '' Drosophila'' gene '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 ...

'' 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 * Small arms proliferation, the spread of ...

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

, 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 (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

, 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 by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

Nomenclature

The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the ''

'' 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'' 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

ANAPC10 Anaphase-promoting complex subunit 10 is an enzyme that in humans is encoded by the ''ANAPC10'' gene. Interactions ANAPC10 has been shown to interact with CDC27, Mothers against decapentaplegic homolog 3 and Mothers against decapentaplegic hom ...

, * 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 v ...

, * HDAC1, *

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 thi ...

, * Insulin receptor, *

LEF1 Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the ''LEF1'' gene. It's a member of T cell factor/lymphoid enhancer factor ( TCF/LEF) family. Function Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nu ...

, * Myc, * MEF2A, *

PIAS3 E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene. PIAS family The mammalian PIAS family consists of four members: PIAS1, PIAS2, PIAS3 and PIAS4. In Drosophila, a single PIAS homologue named dPIAS/Zimp has be ...

, * PIN1, * SKI protein, *

SKIL SKIL Power Tools is a brand of electric power tools and accessories located in Naperville, Illinois, United States. It is a subsidiary of Chervon, a company based in Nanjing, China. The company now focuses more on the do-it-yourself consum ...

, * SMAD3, * SMURF2, * SNW1, *

STRAP A strap, sometimes also called strop, is an elongated wikt:flap, 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 s ...

* WWTR1

Function

Nomenclature

Interactions

References

Further reading