Biology:Mothers against decapentaplegic homolog 2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1][2] 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.

Function

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.[3]

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.

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 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.[4]

Interactions

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



References

  1. ↑ "MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma". Cell 86 (4): 543–52. August 1996. doi:10.1016/S0092-8674(00)80128-2. PMID 8752209. 
  2. ↑ "Mad-related genes in the human". Nat. Genet. 13 (3): 347–9. July 1996. doi:10.1038/ng0796-347. PMID 8673135. 
  3. ↑ "Entrez Gene: SMAD2 SMAD family member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4087. 
  4. ↑ "Sonic Hedgehog, DICER, and the Problem With Naming Genes", Sep 26, 2014, Michael White. psmag.com
  5. ↑ "Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1". BMC Cell Biol. 5: 20. May 2004. doi:10.1186/1471-2121-5-20. PMID 15144564. 
  6. ↑ "The adaptor molecule Disabled-2 links the transforming growth factor β receptors to the Smad pathway". EMBO J. 20 (11): 2789–801. June 2001. doi:10.1093/emboj/20.11.2789. ISSN 0261-4189. PMID 11387212. 
  7. ↑ 7.0 7.1 7.2 7.3 "A Smad transcriptional corepressor". Cell 97 (1): 29–39. April 1999. doi:10.1016/S0092-8674(00)80712-6. ISSN 0092-8674. PMID 10199400. 
  8. ↑ 8.0 8.1 "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6198–203. May 2001. doi:10.1073/pnas.101579798. ISSN 0027-8424. PMID 11371641. Bibcode: 2001PNAS...98.6198P. 
  9. ↑ "FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor β Signals". Mol. Cell. Biol. 19 (1): 424–30. January 1999. doi:10.1128/MCB.19.1.424. ISSN 0270-7306. PMID 9858566. 
  10. ↑ "Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes". Genes Dev. 11 (23): 3157–67. December 1997. doi:10.1101/gad.11.23.3157. ISSN 0890-9369. PMID 9389648. 
  11. ↑ "BF-1 Interferes with Transforming Growth Factor β Signaling by Associating with Smad Partners". Mol. Cell. Biol. 20 (17): 6201–11. September 2000. doi:10.1128/MCB.20.17.6201-6211.2000. ISSN 0270-7306. PMID 10938097. 
  12. ↑ "Smad4 and FAST-1 in the assembly of activin-responsive factor". Nature 389 (6646): 85–9. September 1997. doi:10.1038/38008. ISSN 0028-0836. PMID 9288972. Bibcode: 1997Natur.389...85C. 
  13. ↑ "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". J. Biol. Chem. 272 (15): 10035–40. April 1997. doi:10.1074/jbc.272.15.10035. ISSN 0021-9258. PMID 9092546. 
  14. ↑ "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". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8358–63. July 2000. doi:10.1073/pnas.150152697. ISSN 0027-8424. PMID 10890911. Bibcode: 2000PNAS...97.8358L. 
  15. ↑ "Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B)". Mol. Cell 9 (1): 133–43. January 2002. doi:10.1016/S1097-2765(01)00430-0. ISSN 1097-2765. PMID 11804592. 
  16. ↑ "Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins". Nucleic Acids Res. 29 (3): 732–42. February 2001. doi:10.1093/nar/29.3.732. PMID 11160896. 
  17. ↑ "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proc. Natl. Acad. Sci. U.S.A. 101 (1): 99–104. January 2004. doi:10.1073/pnas.0307598100. ISSN 0027-8424. PMID 14691252. Bibcode: 2004PNAS..101...99L. 
  18. ↑ 18.0 18.1 "Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins". J. Biol. Chem. 284 (10): 6109–15. March 2009. doi:10.1074/jbc.M804659200. ISSN 0021-9258. PMID 19122240. 
  19. ↑ "Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation". J. Biol. Chem. 278 (40): 38998–9005. October 2003. doi:10.1074/jbc.M307112200. ISSN 0021-9258. PMID 12874272. 
  20. ↑ "The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling". Genes Dev. 13 (17): 2196–206. September 1999. doi:10.1101/gad.13.17.2196. ISSN 0890-9369. PMID 10485843. 
  21. ↑ "Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN". Genes Dev. 15 (21): 2822–36. November 2001. doi:10.1101/gad.912901. ISSN 0890-9369. PMID 11691834. 
  22. ↑ "Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein". Science 286 (5440): 771–4. October 1999. doi:10.1126/science.286.5440.771. ISSN 0036-8075. PMID 10531062. https://zenodo.org/record/1231169. 
  23. ↑ "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4". EMBO J. 16 (17): 5353–62. September 1997. doi:10.1093/emboj/16.17.5353. ISSN 0261-4189. PMID 9311995. 
  24. ↑ "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. 13 (1): 15–23. January 1999. doi:10.1210/mend.13.1.0218. ISSN 0888-8809. PMID 9892009. 
  25. ↑ "Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling". J. Biol. Chem. 275 (47): 36818–22. November 2000. doi:10.1074/jbc.C000580200. ISSN 0021-9258. PMID 11016919. 
  26. ↑ "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation". Nat. Cell Biol. 3 (6): 587–95. June 2001. doi:10.1038/35078562. ISSN 1465-7392. PMID 11389444. 
  27. ↑ "Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription". J. Biol. Chem. 276 (21): 18243–8. May 2001. doi:10.1074/jbc.M010815200. ISSN 0021-9258. PMID 11278756. 
  28. ↑ "STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling". Mol. Cell. Biol. 20 (9): 3157–67. May 2000. doi:10.1128/MCB.20.9.3157-3167.2000. ISSN 0270-7306. PMID 10757800. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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