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Genetics Home Reference: your guide to understanding genetic conditions
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SMAD gene family

Reviewed March 2012

What are the SMAD genes?

Genes in the SMAD gene family provide instructions for producing proteins that help regulate the activity of particular genes as well as cell growth and division (proliferation). The proteins carry out these functions as part of the transforming growth factor beta (TGF-β) pathway, which transmits signals from the outside of the cell to the nucleus. This type of signaling pathway allows the environment outside the cell to affect how the cell produces other proteins.

The signaling process begins when a protein called TGF-β attaches (binds) to a receptor on the surface of the cell, which then turns on (activates) a group of SMAD proteins (called receptor-regulated SMADs or R-SMADs). The R-SMADs include the SMAD1, SMAD2, SMAD3, SMAD5, and SMAD8 proteins. These R-SMADs then bind together in multiple protein groups (or complexes) with another SMAD protein, SMAD4, also called the common mediator SMAD (or Co-SMAD). Once the SMAD protein complexes form, they are transported to the nucleus. In the nucleus, the SMAD complexes bind to specific areas of DNA, where they control the activity of particular genes and regulate cell proliferation.

When the signaling pathway needs to be turned off, two SMAD proteins, SMAD6 and SMAD7 (known as the inhibitory SMADs or I-SMADs), inactivate the receptors for the TFG-β protein on the cell surface. The I-SMADs are also thought to interfere with the formation of SMAD-SMAD4 complexes and interfere with the interaction between the SMAD complex and DNA in the cell nucleus.

Which genes are included in the SMAD gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides a list of genes in the SMAD family (http://www.genenames.org/genefamily/smad.php).

Genetics Home Reference summarizes the normal function and health implications of these members of the SMAD gene family: SMAD3 and SMAD4.

What conditions are related to genes in the SMAD gene family?

Genetics Home Reference includes these conditions related to genes in the SMAD gene family:

  • familial thoracic aortic aneurysm and dissection
  • hereditary hemorrhagic telangiectasia
  • juvenile polyposis syndrome
  • Loeys-Dietz syndrome
  • Myhre syndrome

Where can I find additional information about the SMAD gene family?

You may find the following resources about the SMAD gene family helpful.

  • Genomes (second edition, 2002): SMAD Signaling in Vertebrates (http://www.ncbi.nlm.nih.gov/books/NBK21127/box/A7928/) (U.S. National Library of Medicine)
  • Developmental Biology (sixth edition, 2000): The Smad Pathway Activated by TGF-β Superfamily Ligands (figure) (http://www.ncbi.nlm.nih.gov/books/NBK10043/figure/A1057/) (U.S. National Library of Medicine)
  • Molecular Biology of the Cell (fourth edition, 2002): Signal Proteins of the TGF-β Superfamily Act Through Receptor Serine/Threonine Kinases and Smads (http://www.ncbi.nlm.nih.gov/books/NBK26822/)

What glossary definitions help with understanding the SMAD gene family?

cell ; cell nucleus ; cell proliferation ; DNA ; domain ; gene ; growth factor ; homologs ; ligand ; nucleus ; proliferation ; protein ; receptor ; transcription ; transcription factor ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

These sources were used to develop the Genetics Home Reference summary for the SMAD gene family.

  • Ross S, Hill CS. How the Smads regulate transcription. Int J Biochem Cell Biol. 2008;40(3):383-408. Epub 2007 Oct 7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18061509?dopt=Abstract)
  • Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007 Dec;8(12):970-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18000526?dopt=Abstract)
  • Hill CS. Nucleocytoplasmic shuttling of Smad proteins. Cell Res. 2009 Jan;19(1):36-46. doi: 10.1038/cr.2008.325. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19114992?dopt=Abstract)
  • Xu L. Regulation of Smad activities. Biochim Biophys Acta. 2006 Nov-Dec;1759(11-12):503-13. Epub 2006 Nov 15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17182123?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2012
Published: November 17, 2014