Mothers against decapentaplegic homolog 2
Encyclopedia
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
gene Sma. SMAD proteins are signal transducers
and transcriptional modulators
that mediate multiple signaling pathways.
, and thus regulates multiple cellular processes, such as cell proliferation
, apoptosis
, 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
, where it binds to target promoters and forms a transcription repressor
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
.
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, like that of Sonic hedgehog
, has been criticized for its frivolity .
with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SMAD2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. MAD homolog 2 belongs to the SMAD
SMAD (protein)
SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream TGF-β gene transcription....
, a family of proteins similar to the gene products of the Drosophila
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
gene 'mothers against decapentaplegic' (Mad) and the C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
gene Sma. SMAD proteins are signal transducers
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
and transcriptional modulators
Regulation of gene expression
Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...
that mediate multiple signaling pathways.
Function
SMAD2 mediates the signal of the transforming growth factor (TGF)-betaTransforming growth factor beta superfamily
The transforming growth factor beta superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983....
, and thus regulates multiple cellular processes, such as cell proliferation
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, and differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
. 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
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
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
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where it binds to target promoters and forms a transcription repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase
ACVR1B
Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.ACVR1B or ALK-4 acts as a transducer of activin or activin like ligands signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3...
, 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
Transforming growth factor beta superfamily
The transforming growth factor beta superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983....
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
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
.
Nomenclature
The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegansCaenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
protein SMA. The name is a combination of the two. During Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...
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
Mothers Against Drunk Driving is a non-profit organization in the United States that seeks to stop drunk driving, support those affected by drunk driving, prevent underage drinking, and overall push for stricter alcohol policy...
, or (MADD). The nomenclature for this protein, like that of Sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
, has been criticized for its frivolity .
Interactions
Mothers against decapentaplegic homolog 2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- ANAPC10ANAPC10Anaphase-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 homolog 2....
, - DAB2DAB2Disabled homolog 2 is a protein that in humans is encoded by the DAB2 gene.-Interactions:DAB2 has been shown to interact with C-src tyrosine kinase, Cdk1, Src, LRP2, DVL3, PIN1, MYO6, DVL2, DAB2IP, Mothers against decapentaplegic homolog 3 and Mothers against decapentaplegic homolog 2.-Further...
, - EP300EP300E1A binding protein p300 also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body...
, - FOXH1FOXH1Forkhead box protein H1 is a protein that in humans is encoded by the FOXH1 gene.-Interactions:FOXH1 has been shown to interact with DRAP1 and Mothers against decapentaplegic homolog 2....
, - HDAC1HDAC1Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, - TGIF1Homeobox protein TGIF1Homeobox 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 :...
, - Insulin receptorInsulin receptorIn molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
, - LEF1Lymphoid enhancer-binding factor 1Lymphoid enhancer-binding factor 1 is a protein that in humans is encoded by the LEF1 gene.- Function :Lymphoid enhancer-binding factor-1 is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha enhancer and confers...
, - MycMycMyc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
, - MEF2AMyocyte-specific enhancer factor 2AMyocyte-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...
, - PIAS3PIAS3E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene.-Interactions:PIAS3 has been shown to interact with GFI1, RELA, Mothers against decapentaplegic homolog 3, Microphthalmia-associated transcription factor, HMGA2 and Mothers against decapentaplegic homolog...
, - PIN1PIN1Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 is an enzyme that in humans is encoded by the PIN1 gene.-Interactions:PIN1 has been shown to interact with CSNK2A2, Casein kinase 2, alpha 1, Wee1-like protein kinase, FOXO4, CDC25C, CDC27, MYT1, PLK1, MPHOSPH1, DAB2, P53, PKMYT1, C-jun,...
, - SKI proteinSKI proteinThe Ski protein is a nuclear protooncoprotein that is associated with tumors at high cellular concentrations. Ski has been shown to interfere with normal cellular functioning by both directly impeding expression of certain genes inside the nucleus of the cell as well as disrupting signaling...
, - SKILSKILSki-like protein is a protein that in humans is encoded by the SKIL gene.-Interactions:SKIL has been shown to interact with SKI protein, Mothers against decapentaplegic homolog 3 and Mothers against decapentaplegic homolog 2.-Further reading:...
, - SMAD3Mothers against decapentaplegic homolog 3Mothers 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 family of proteins.The human SMAD3 gene is located on chromosome 15...
, - SMURF2SMURF2E3 ubiquitin-protein ligase SMURF2 is an enzyme that in humans is encoded by the SMURF2 gene.-Interactions:SMURF2 has been shown to interact with Mothers against decapentaplegic homolog 7, SCYE1, SMURF1, Mothers against decapentaplegic homolog 3, Ubiquitin C, Mothers against decapentaplegic homolog...
, - SNW1SNW1SNW domain-containing protein 1 is a protein that in humans is encoded by the SNW1 gene.-Interactions:SNW1 has been shown to interact with Histone deacetylase 2, SKI protein, Retinoblastoma protein, PABPN1, CIR, RBPJ, Nuclear receptor coactivator 1, Nuclear receptor co-repressor 2, Calcitriol...
, - STRAPSTRAPSerine-threonine kinase receptor-associated protein is an enzyme that in humans is encoded by the STRAP gene.-Interactions:STRAP has been shown to interact with Mothers against decapentaplegic homolog 6, TGF beta receptor 2, Mothers against decapentaplegic homolog 7, TGF beta receptor 1, Mothers...