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Gene Ontology Classifications
SMAD family member 2

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GO curators for mouse genes have assigned the following annotations to the gene product of Smad2. (This text reflects annotations as of Tuesday, May 26, 2015.)
Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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 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 have been observed for this gene. [provided by RefSeq, May 2012]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
  1. Baburajendran N et al. (2011) Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers. Nucleic Acids Res, 39:8213-22. (PubMed:21724602)
  2. Bailey JS et al. (2004) Activin regulation of the follicle-stimulating hormone beta-subunit gene involves Smads and the TALE homeodomain proteins Pbx1 and Prep1. Mol Endocrinol, 18:1158-70. (PubMed:14764653)
  3. Brennan J et al. (2001) Nodal signalling in the epiblast patterns the early mouse embryo. Nature, 411:965-9. (PubMed:11418863)
  4. Chou YT et al. (2006) Cited2 modulates TGF-beta-mediated upregulation of MMP9. Oncogene, 25:5547-60. (PubMed:16619037)
  5. Colas AR et al. (2012) Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes Dev, 26:2567-79. (PubMed:23152446)
  6. Collart C et al. (2005) Smicl is a novel Smad interacting protein and cleavage and polyadenylation specificity factor associated protein. Genes Cells, 10:897-906. (PubMed:16115198)
  7. Costello I et al. (2011) The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation. Nat Cell Biol, 13:1084-91. (PubMed:21822279)
  8. da Silva S et al. (2011) Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-{beta} signaling. Proc Natl Acad Sci U S A, 108:3395-400. (PubMed:21300867)
  9. Dunn NR et al. (2004) Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo. Development, 131:1717-28. (PubMed:15084457)
  10. Goto Y et al. (2007) Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets. Dev Dyn, 236:2865-74. (PubMed:17849440)
  11. Ito Y et al. (2001) Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development. J Biol Chem, 276:44163-72. (PubMed:11557747)
  12. Izzi L et al. (2007) Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development. EMBO J, 26:3132-43. (PubMed:17568773)
  13. Labbe E et al. (1998) Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. Mol Cell, 2:109-20. (PubMed:9702197)
  14. Li M et al. (2008) Mesodermal Deletion of Transforming Growth Factor-{beta} Receptor II Disrupts Lung Epithelial Morphogenesis: cross-talk between TGF-{beta} and Sonic hedgehog pathways. J Biol Chem, 283:36257-64. (PubMed:18990706)
  15. Liu Y et al. (2004) Smad2 and Smad3 coordinately regulate craniofacial and endodermal development. Dev Biol, 270:411-26. (PubMed:15183723)
  16. Maeda S et al. (2004) Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J, 23:552-563. (PubMed:14749725)
  17. Nawshad A et al. (2003) TGF{beta}3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development. J Cell Biol, 163:1291-1301. (PubMed:14691138)
  18. Quinn ZA et al. (2001) Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res, 29:732-42. (PubMed:11160896)
  19. Redshaw N et al. (2013) TGF-beta/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos. PLoS One, 8:e55186. (PubMed:23390484)
  20. Ring C et al. (2002) The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling. Genes Dev, 16:820-35. (PubMed:11937490)
  21. Subramanian SV et al. (2004) Induction of vascular smooth muscle alpha-actin gene transcription in transforming growth factor beta1-activated myofibroblasts mediated by dynamic interplay between the Pur repressor proteins and Sp1/Smad coactivators. Mol Biol Cell, 15:4532-43. (PubMed:15282343)
  22. Vincent SD et al. (2003) Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev, 17:1646-62. (PubMed:12842913)
  23. Waldrip WR et al. (1998) Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell, 92:797-808. (PubMed:9529255)
  24. Warner DR et al. (2003) Identification of novel Smad binding proteins. Biochem Biophys Res Commun, 312:1185-90. (PubMed:14651998)
  25. Wilkinson DS et al. (2008) Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. Mol Cell Biol, 28:1988-98. (PubMed:18212064)
  26. Wilkinson DS et al. (2005) A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol Cell Biol, 25:1200-12. (PubMed:15657445)
  27. Zhang J et al. (2007) Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci, 10:77-86. (PubMed:17159989)
  28. Zieba A et al. (2012) Intercellular variation in signaling through the TGF-beta pathway and its relation to cell density and cell cycle phase. Mol Cell Proteomics, 11:M111.013482. (PubMed:22442258)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement


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