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Mothers against decapentaplegic homolog 2: Wikis

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SMAD family member 2

PDB rendering based on 1dev.
Available structures
1dev, 1khx, 1mjs, 1mk2, 1u7f, 1u7v
Identifiers
Symbols SMAD2; JV18; JV18-1; MADH2; MADR2; MGC22139; MGC34440; hMAD-2; hSMAD2
External IDs OMIM601366 MGI108051 HomoloGene21197 GeneCards: SMAD2 Gene
RNA expression pattern
PBB GE SMAD2 203075 at tn.png
PBB GE SMAD2 203076 s at tn.png
PBB GE SMAD2 203077 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4087 17126
Ensembl ENSG00000175387 ENSMUSG00000024563
UniProt Q15796 Q8C2P1
RefSeq (mRNA) NM_001003652 NM_010754
RefSeq (protein) NP_001003652 NP_034884
Location (UCSC) Chr 18:
43.62 - 43.71 Mb
Chr 18:
76.37 - 76.43 Mb
PubMed search [1] [2]

SMAD2 is a human gene.[1][2]

The protein encoded by this gene 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. This protein 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.

Contents

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 eg. Mothers Against Drunk Driving or (MADD). The nomenclature for this protein, like that of Sonic hedgehog, has been criticized for its frivolity.

Interactions

Mothers against decapentaplegic homolog 2 has been shown to interact with Homeobox protein TGIF1,[4][5] Myocyte-specific enhancer factor 2A,[6] ANAPC10,[7] Insulin receptor,[8] PIN1,[9] Mothers against decapentaplegic homolog 3,[10][11] Lymphoid enhancer-binding factor 1,[12] HDAC1,[4] SKIL,[13][14] SKI protein,[15][16] Myc,[17] SNW1,[18] SMURF2,[19][20][9] DAB2,[21] EP300,[4][5] PIAS3,[22] STRAP[23] and FOXH1.[4][24][25][26][27]

References

  1. ^ Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S, Andrulis IL, Thomsen GH, Wrana JL, Attisano L (August 1996). "MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma". Cell 86 (4): 543–52. doi:10.1016/S0092-8674(00)80128-2. PMID 8752209.  
  2. ^ Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (July 1996). "Mad-related genes in the human". Nat. Genet. 13 (3): 347–9. doi:10.1038/ng0796-347. PMID 8673135.  
  3. ^ "Entrez Gene: SMAD2 SMAD family member 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4087.  
  4. ^ a b c d Wotton, D; Lo R S, Lee S, Massagué J (Apr. 1999). "A Smad transcriptional corepressor". Cell (UNITED STATES) 97 (1): 29–39. ISSN 0092-8674. PMID 10199400.  
  5. ^ a b Pessah, M; Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F, Gauthier J M, Atfi A (May. 2001). "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (11): 6198–203. doi:10.1073/pnas.101579798. ISSN 0027-8424. PMID 11371641.  
  6. ^ Quinn, Z A; Yang C C, Wrana J L, McDermott J C (Feb. 2001). "Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins". Nucleic Acids Res. (England) 29 (3): 732–42. PMID 11160896.  
  7. ^ Nourry, Claire; Maksumova Lola, Pang Mona, Liu Xiaohong, Wang Tongwen (May. 2004). "Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1". BMC Cell Biol. (England) 5: 20. doi:10.1186/1471-2121-5-20. PMID 15144564.  
  8. ^ O'Neill, T J; Zhu Y, Gustafson T A (Apr. 1997). "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. (UNITED STATES) 272 (15): 10035–40. ISSN 0021-9258. PMID 9092546.  
  9. ^ a b Nakano, Ayako; Koinuma Daizo, Miyazawa Keiji, Uchida Takafumi, Saitoh Masao, Kawabata Masahiro, Hanai Jun-ichi, Akiyama Hirotada, Abe Masahiro, Miyazono Kohei, Matsumoto Toshio, Imamura Takeshi (Mar. 2009). "Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins". J. Biol. Chem. (United States) 284 (10): 6109–15. doi:10.1074/jbc.M804659200. ISSN 0021-9258. PMID 19122240.  
  10. ^ Nakao, A; Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin C H, Miyazono K, ten Dijke P (Sep. 1997). "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4". EMBO J. (ENGLAND) 16 (17): 5353–62. doi:10.1093/emboj/16.17.5353. ISSN 0261-4189. PMID 9311995.  
  11. ^ Lebrun, J J; Takabe K, Chen Y, Vale W (Jan. 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. (UNITED STATES) 13 (1): 15–23. ISSN 0888-8809. PMID 9892009.  
  12. ^ Labbé, E; Letamendia A, Attisano L (Jul. 2000). "Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (15): 8358–63. doi:10.1073/pnas.150152697. ISSN 0027-8424. PMID 10890911.  
  13. ^ Stroschein, S L; Bonni S, Wrana J L, Luo K (Nov. 2001). "Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN". Genes Dev. (United States) 15 (21): 2822–36. doi:10.1101/gad.912901. ISSN 0890-9369. PMID 11691834.  
  14. ^ Stroschein, S L; Wang W, Zhou S, Zhou Q, Luo K (Oct. 1999). "Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein". Science (UNITED STATES) 286 (5440): 771–4. ISSN 0036-8075. PMID 10577218.  
  15. ^ Harada, Jun; Kokura Kenji, Kanei-Ishii Chie, Nomura Teruaki, Khan Md Matiullah, Kim Yongsok, Ishii Shunsuke (Oct. 2003). "Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation". J. Biol. Chem. (United States) 278 (40): 38998–9005. doi:10.1074/jbc.M307112200. ISSN 0021-9258. PMID 12874272.  
  16. ^ Luo, K; Stroschein S L, Wang W, Chen D, Martens E, Zhou S, Zhou Q (Sep. 1999). "The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling". Genes Dev. (UNITED STATES) 13 (17): 2196–206. ISSN 0890-9369. PMID 10485843.  
  17. ^ Feng, Xin-Hua; Liang Yao-Yun, Liang Min, Zhai Weiguo, Lin Xia (Jan. 2002). "Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B)". Mol. Cell (United States) 9 (1): 133–43. ISSN 1097-2765. PMID 11804592.  
  18. ^ Leong, G M; Subramaniam N, Figueroa J, Flanagan J L, Hayman M J, Eisman J A, Kouzmenko A P (May. 2001). "Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription". J. Biol. Chem. (United States) 276 (21): 18243–8. doi:10.1074/jbc.M010815200. ISSN 0021-9258. PMID 11278756.  
  19. ^ Lin, X; Liang M, Feng X H (Nov. 2000). "Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling". J. Biol. Chem. (UNITED STATES) 275 (47): 36818–22. doi:10.1074/jbc.C000580200. ISSN 0021-9258. PMID 11016919.  
  20. ^ Bonni, S; Wang H R, Causing C G, Kavsak P, Stroschein S L, Luo K, Wrana J L (Jun. 2001). "TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation". Nat. Cell Biol. (England) 3 (6): 587–95. doi:10.1038/35078562. ISSN 1465-7392. PMID 11389444.  
  21. ^ Hocevar, B A; Smine A, Xu X X, Howe P H (Jun. 2001). "The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway". EMBO J. (England) 20 (11): 2789–801. doi:10.1093/emboj/20.11.2789. ISSN 0261-4189. PMID 11387212.  
  22. ^ Long, Jianyin; Wang Guannan, Matsuura Isao, He Dongming, Liu Fang (Jan. 2004). "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proc. Natl. Acad. Sci. U.S.A. (United States) 101 (1): 99–104. doi:10.1073/pnas.0307598100. ISSN 0027-8424. PMID 14691252.  
  23. ^ Datta, P K; Moses H L (May. 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3157–67. ISSN 0270-7306. PMID 10757800.  
  24. ^ Liu, B; Dou C L, Prabhu L, Lai E (Jan. 1999). "FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor beta signals". Mol. Cell. Biol. (UNITED STATES) 19 (1): 424–30. ISSN 0270-7306. PMID 9858566.  
  25. ^ Liu, F; Pouponnot C, Massagué J (Dec. 1997). "Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes". Genes Dev. (UNITED STATES) 11 (23): 3157–67. ISSN 0890-9369. PMID 9389648.  
  26. ^ Dou, C; Lee J, Liu B, Liu F, Massague J, Xuan S, Lai E (Sep. 2000). "BF-1 interferes with transforming growth factor beta signaling by associating with Smad partners". Mol. Cell. Biol. (UNITED STATES) 20 (17): 6201–11. ISSN 0270-7306. PMID 10938097.  
  27. ^ Chen, X; Weisberg E, Fridmacher V, Watanabe M, Naco G, Whitman M (Sep. 1997). "Smad4 and FAST-1 in the assembly of activin-responsive factor". Nature (ENGLAND) 389 (6646): 85–9. doi:10.1038/38008. ISSN 0028-0836. PMID 9288972.  

Further reading

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

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