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Mothers against decapentaplegic homolog 3: Wikis


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SMAD family member 3

PDB rendering based on 1dev.
Available structures
1dev, 1khx, 1mhd, 1mjs, 1mk2, 1ozj, 1u7f, 1u7v
Symbols SMAD3; DKFZP586N0721; DKFZp686J10186; HSPC193; HsT17436; JV15-2; MADH3; MGC60396; Smad 3
External IDs OMIM603109 MGI1201674 HomoloGene55937 GeneCards: SMAD3 Gene
RNA expression pattern
PBB GE SMAD3 205396 at tn.png
PBB GE SMAD3 205397 x at tn.png
PBB GE SMAD3 205398 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4088 17127
Ensembl ENSG00000166949 ENSMUSG00000032402
UniProt P84022 Q3V3E0
RefSeq (mRNA) NM_005902 NM_016769
RefSeq (protein) NP_005893 NP_058049
Location (UCSC) Chr 15:
65.15 - 65.27 Mb
Chr 9:
63.44 - 63.56 Mb
PubMed search [1] [2]

SMAD family member 3, also known as SMAD3, is a human gene.[1]

SMAD3 or Mothers against decapentaplegic homolog 3 is a gene which appears in humans on chromosome 15. It is one of several human homologues of a gene which was originally discovered in the fruit fly Drosophila melanogaster.

The name SMAD3 also refers to a member of the SMAD family of proteins.


SMAD3 gene

The SMAD3 gene codes for the SMAD3 protein. It consists of 9 exons over 129,339 base pairs.

In mice, mutation of SMAD3 has been associated with colorectal adenocarcinoma, increased systemic inflammation, and accelerated wound healing. There is no conclusive evidence of similar activity in humans, however. A 2002 study investigated possible links between SMAD3 mutation and cancer of the pancreas and parathyroid gland, but found no connection. Increased SMAD3 activity has, however, been implicated in the pathogenesis of scleroderma.

The herpes simplex virus can downregulate SMAD3 using the Lat transcription factor, even while the virus is in a latent state.

A reference assembly of SMAD3 is available.

SMAD3 protein

SMAD3 or Mothers against decapentaplegic homolog 3 is a polypeptide that, as its name describes, is a homolog of the Drosophila protein "Mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members, SMAD3 is involved in cell signalling. SMAD3 modulates signals of activin and TGFβ's. Binding of this protein with SMAD4 enables its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. SMAD3 is a receptor-regulated SMAD (R-SMAD).


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 inspired by organizations formed by mothers to oppose social problems, such as Mothers Against Drunk Driving (MADD).


Further reading

  • Li H, Liu JP (2008). "Mechanisms of action of TGF-beta in cancer: evidence for Smad3 as a repressor of the hTERT gene.". Ann. N. Y. Acad. Sci. 1114: 56–68. doi:10.1196/annals.1396.016. PMID 17934056.  
  • Matsuzaki K (2006). "Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis.". Histol. Histopathol. 21 (6): 645–62. PMID 16528675.  
  • Miyazono K (2000). "TGF-beta signaling by Smad proteins.". Cytokine Growth Factor Rev. 11 (1-2): 15–22. doi:10.1016/S1359-6101(99)00025-8. PMID 10708949.  
  • Wrana JL, Attisano L (2000). "The Smad pathway.". Cytokine Growth Factor Rev. 11 (1-2): 5–13. doi:10.1016/S1359-6101(99)00024-6. PMID 10708948.  
  • Verschueren K, Huylebroeck D (2000). "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells.". Cytokine Growth Factor Rev. 10 (3-4): 187–99. doi:10.1016/S1359-6101(99)00012-X. PMID 10647776.  
  • Massagué J (1998). "TGF-beta signal transduction.". Annu. Rev. Biochem. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.  
  • Walker LC, Waddell N, Ten Haaf A, et al. (2008). "Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers.". Breast Cancer Research and Treatment 112: 229. doi:10.1007/s10549-007-9848-5. PMID 18095154.  
  • Lee KB, Jeon JH, Choi I, et al. (2008). "Clusterin, a novel modulator of TGF-beta signaling, is involved in Smad2/3 stability.". Biochem. Biophys. Res. Commun. 366 (4): 905–9. doi:10.1016/j.bbrc.2007.12.033. PMID 18082619.  
  • Kim TD, Shin S, Janknecht R (2008). "Repression of Smad3 activity by histone demethylase SMCX/JARID1C.". Biochem. Biophys. Res. Commun. 366 (2): 563–7. doi:10.1016/j.bbrc.2007.12.013. PMID 18078810.  
  • Zhao X, Nicholls JM, Chen YG (2008). "Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signaling.". J. Biol. Chem. 283 (6): 3272–80. doi:10.1074/jbc.M708033200. PMID 18055455.  
  • Li T, Chiang JY (2007). "A novel role of transforming growth factor beta1 in transcriptional repression of human cholesterol 7alpha-hydroxylase gene.". Gastroenterology 133 (5): 1660–9. doi:10.1053/j.gastro.2007.08.042. PMID 17920062.  
  • Lu S, Lee J, Revelo M, et al. (2007). "Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice.". Clin. Cancer Res. 13 (19): 5692–702. doi:10.1158/1078-0432.CCR-07-1078. PMID 17908958.  
  • Kalo E, Buganim Y, Shapira KE, et al. (2007). "Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II.". Mol. Cell. Biol. 27 (23): 8228–42. doi:10.1128/MCB.00374-07. PMID 17875924.  
  • Weng HL, Ciuclan L, Liu Y, et al. (2007). "Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes.". Hepatology 46 (4): 1257–70. doi:10.1002/hep.21806. PMID 17657819.  
  • Dennler S, André J, Alexaki I, et al. (2007). "Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo.". Cancer Res. 67 (14): 6981–6. doi:10.1158/0008-5472.CAN-07-0491. PMID 17638910.  
  • Zhang M, Lee CH, Luo DD, et al. (2007). "Polarity of response to transforming growth factor-beta1 in proximal tubular epithelial cells is regulated by beta-catenin.". J. Biol. Chem. 282 (39): 28639–47. doi:10.1074/jbc.M700594200. PMID 17623674.  
  • Martin MM, Buckenberger JA, Jiang J, et al. (2007). "TGF-beta1 stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways.". Am. J. Physiol. Lung Cell Mol. Physiol. 293 (3): L790–9. doi:10.1152/ajplung.00099.2007. PMID 17601799.  
  • Dai F, Chang C, Lin X, et al. (2007). "Erbin inhibits transforming growth factor beta signaling through a novel Smad-interacting domain.". Mol. Cell. Biol. 27 (17): 6183–94. doi:10.1128/MCB.00132-07. PMID 17591701.  
  • Levy L, Howell M, Das D, et al. (2007). "Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation.". Mol. Cell. Biol. 27 (17): 6068–83. doi:10.1128/MCB.00664-07. PMID 17591695.  


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