mothers against decapentaplegic homolog 2

SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, 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.{{cite web | title = Entrez Gene: SMAD2 SMAD family member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4087}}

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.

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 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.[https://psmag.com/sonic-hedgehog-dicer-and-the-problem-with-naming-genes-113c58df8f7a#.os08udsyk "Sonic Hedgehog, DICER, and the Problem With Naming Genes"], Sep 26, 2014, Michael White. psmag.com

Mothers against decapentaplegic homolog 2 has been shown to interact with:

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• ANAPC10,{{cite journal |vauthors=Nourry C, Maksumova L, Pang M, Liu X, Wang T | title = Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1 | journal = BMC Cell Biol. | volume = 5 | pages = 20 | date = May 2004 | pmid = 15144564 | pmc = 420458 | doi = 10.1186/1471-2121-5-20 | doi-access = free }}
• DAB2,{{cite journal |vauthors=Hocevar BA, Smine A, Xu XX, Howe PH | title = The adaptor molecule Disabled-2 links the transforming growth factor β receptors to the Smad pathway | journal = EMBO J. | volume = 20 | issue = 11 | pages = 2789–801 | date = June 2001 | pmid = 11387212 | pmc = 125498 | doi = 10.1093/emboj/20.11.2789 | issn = 0261-4189 }}
• EP300,
• FOXH1,{{cite journal |vauthors=Liu B, Dou CL, Prabhu L, Lai E | title = FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor β Signals | journal = Mol. Cell. Biol. | volume = 19 | issue = 1 | pages = 424–30 | date = January 1999 | pmid = 9858566 | pmc = 83900 | issn = 0270-7306 | doi = 10.1128/MCB.19.1.424 }}{{cite journal |vauthors=Liu F, Pouponnot C, Massagué J | title = Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes | journal = Genes Dev. | volume = 11 | issue = 23 | pages = 3157–67 | date = December 1997 | pmid = 9389648 | pmc = 316747 | doi = 10.1101/gad.11.23.3157 | issn = 0890-9369 }}{{cite journal |vauthors=Dou C, Lee J, Liu B, Liu F, Massague J, Xuan S, Lai E | title = BF-1 Interferes with Transforming Growth Factor β Signaling by Associating with Smad Partners | journal = Mol. Cell. Biol. | volume = 20 | issue = 17 | pages = 6201–11 | date = September 2000 | pmid = 10938097 | pmc = 86095 | doi = 10.1128/MCB.20.17.6201-6211.2000 | issn = 0270-7306 }}{{cite journal |vauthors=Chen X, Weisberg E, Fridmacher V, Watanabe M, Naco G, Whitman M | title = Smad4 and FAST-1 in the assembly of activin-responsive factor | journal = Nature | volume = 389 | issue = 6646 | pages = 85–9 | date = September 1997 | pmid = 9288972 | doi = 10.1038/38008 | bibcode = 1997Natur.389...85C | s2cid = 11927346 | issn = 0028-0836 }}
• HDAC1,
• TGIF1,{{cite journal |vauthors=Wotton D, Lo RS, Lee S, Massagué J | title = A Smad transcriptional corepressor | journal = Cell | volume = 97 | issue = 1 | pages = 29–39 | date = April 1999 | pmid = 10199400 | doi = 10.1016/S0092-8674(00)80712-6 | s2cid = 6907878 | issn = 0092-8674 | doi-access = free }}{{cite journal |vauthors=Pessah M, Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F, Gauthier JM, Atfi A | title = c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 11 | pages = 6198–203 | date = May 2001 | pmid = 11371641 | pmc = 33445 | doi = 10.1073/pnas.101579798 | bibcode = 2001PNAS...98.6198P | issn = 0027-8424 | doi-access = free }}
• Insulin receptor,{{cite journal |vauthors=O'Neill TJ, Zhu Y, Gustafson TA | title = Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation | journal = J. Biol. Chem. | volume = 272 | issue = 15 | pages = 10035–40 | date = April 1997 | pmid = 9092546 | doi = 10.1074/jbc.272.15.10035 | issn = 0021-9258 | doi-access = free }}
• LEF1,{{cite journal |vauthors=Labbé E, Letamendia A, Attisano L | title = Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-β and Wnt pathways | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 15 | pages = 8358–63 | date = July 2000 | pmid = 10890911 | pmc = 26952 | doi = 10.1073/pnas.150152697 | bibcode = 2000PNAS...97.8358L | issn = 0027-8424 | doi-access = free }}
• Myc,{{cite journal |vauthors=Feng XH, Liang YY, Liang M, Zhai W, Lin X | title = Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B) | journal = Mol. Cell | volume = 9 | issue = 1 | pages = 133–43 | date = January 2002 | pmid = 11804592 | doi = 10.1016/S1097-2765(01)00430-0 | issn = 1097-2765 | doi-access = free }}
• MEF2A,{{cite journal |vauthors=Quinn ZA, Yang CC, Wrana JL, McDermott JC | title = Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins | journal = Nucleic Acids Res. | volume = 29 | issue = 3 | pages = 732–42 | date = February 2001 | pmid = 11160896 | pmc = 30396 | doi = 10.1093/nar/29.3.732 }}
• PIAS3,{{cite journal |vauthors=Long J, Wang G, Matsuura I, He D, Liu F | title = Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 1 | pages = 99–104 | date = January 2004 | pmid = 14691252 | pmc = 314145 | doi = 10.1073/pnas.0307598100 | bibcode = 2004PNAS..101...99L | issn = 0027-8424 | doi-access = free }}
• PIN1,{{cite journal |vauthors=Nakano A, Koinuma D, Miyazawa K, Uchida T, Saitoh M, Kawabata M, Hanai J, Akiyama H, Abe M, Miyazono K, Matsumoto T, Imamura T | title = Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins | journal = J. Biol. Chem. | volume = 284 | issue = 10 | pages = 6109–15 | date = March 2009 | pmid = 19122240 | doi = 10.1074/jbc.M804659200 | issn = 0021-9258 | doi-access = free }}
• SKI protein,{{cite journal |vauthors=Harada J, Kokura K, Kanei-Ishii C, Nomura T, Khan MM, Kim Y, Ishii S | title = Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation | journal = J. Biol. Chem. | volume = 278 | issue = 40 | pages = 38998–9005 | date = October 2003 | pmid = 12874272 | doi = 10.1074/jbc.M307112200 | issn = 0021-9258 | doi-access = free }}{{cite journal |vauthors=Luo K, Stroschein SL, Wang W, Chen D, Martens E, Zhou S, Zhou Q | title = The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling | journal = Genes Dev. | volume = 13 | issue = 17 | pages = 2196–206 | date = September 1999 | pmid = 10485843 | pmc = 316985 | doi = 10.1101/gad.13.17.2196 | issn = 0890-9369 }}
• SKIL,{{cite journal |vauthors=Stroschein SL, Bonni S, Wrana JL, Luo K | title = Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN | journal = Genes Dev. | volume = 15 | issue = 21 | pages = 2822–36 | date = November 2001 | pmid = 11691834 | pmc = 312804 | doi = 10.1101/gad.912901 | issn = 0890-9369 }}{{cite journal |vauthors=Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K | title = Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein | journal = Science | volume = 286 | issue = 5440 | pages = 771–4 | date = October 1999 | pmid = 10531062 | doi = 10.1126/science.286.5440.771 | issn = 0036-8075 | url = https://zenodo.org/record/1231169 }}
• SMAD3,{{cite journal |vauthors=Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P | title = TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4 | journal = EMBO J. | volume = 16 | issue = 17 | pages = 5353–62 | date = September 1997 | pmid = 9311995 | pmc = 1170167 | doi = 10.1093/emboj/16.17.5353 | issn = 0261-4189 }}{{cite journal |vauthors=Lebrun JJ, Takabe K, Chen Y, Vale W | title = Roles of pathway-specific and inhibitory Smads in activin receptor signaling | journal = Mol. Endocrinol. | volume = 13 | issue = 1 | pages = 15–23 | date = January 1999 | pmid = 9892009 | doi = 10.1210/mend.13.1.0218 | s2cid = 26825706 | issn = 0888-8809 | doi-access = free }}
• SMURF2,{{cite journal |vauthors=Lin X, Liang M, Feng XH | title = Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling | journal = J. Biol. Chem. | volume = 275 | issue = 47 | pages = 36818–22 | date = November 2000 | pmid = 11016919 | doi = 10.1074/jbc.C000580200 | issn = 0021-9258 | doi-access = free }}{{cite journal |vauthors=Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL | title = TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation | journal = Nat. Cell Biol. | volume = 3 | issue = 6 | pages = 587–95 | date = June 2001 | pmid = 11389444 | doi = 10.1038/35078562 | s2cid = 23270947 | issn = 1465-7392 }}
• SNW1,{{cite journal |vauthors=Leong GM, Subramaniam N, Figueroa J, Flanagan JL, Hayman MJ, Eisman JA, Kouzmenko AP | title = Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription | journal = J. Biol. Chem. | volume = 276 | issue = 21 | pages = 18243–8 | date = May 2001 | pmid = 11278756 | doi = 10.1074/jbc.M010815200 | issn = 0021-9258 | doi-access = free }}
• STRAP{{cite journal |vauthors=Datta PK, Moses HL | title = STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling | journal = Mol. Cell. Biol. | volume = 20 | issue = 9 | pages = 3157–67 | date = May 2000 | pmid = 10757800 | pmc = 85610 | doi = 10.1128/MCB.20.9.3157-3167.2000 | issn = 0270-7306 }}
• WWTR1

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{{PDB Gallery|geneid=4087}}

{{TGF beta signaling}}

{{Transcription factors|g1}}

{{Tumor suppressor genes}}

{{TGFβ receptor superfamily modulators}}

{{NLM content}}

{{DEFAULTSORT:Mothers Against Decapentaplegic Homolog 2}}

Category:Developmental genes and proteins

Category:MH1 domain

Category:MH2 domain

Category:R-SMAD

Category:Transcription factors

Category:Human proteins