D
IPR001132

SMAD domain, Dwarfin-type

InterPro entry
Short nameSMAD_dom_Dwarfin-type
Overlapping
homologous
superfamilies
 

Description

Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth
[3, 4]
. The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signalling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp
[2, 5]
. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF)
[6]
.

This entry represents the SMAD (Mothers against decapentaplegic (MAD) homologue) (also called MH2 for MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five α helices and three loops enclosing a β sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C terminus of MH2
[3, 2, 1]
.

References

1.The Smads. Attisano L, Lee-Hoeflich ST. Genome Biol. 2, REVIEWS3010, (2001). View articlePMID: 11532220

2.Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Kim J, Johnson K, Chen HJ, Carroll S, Laughon A. Nature 388, 304-8, (1997). View articlePMID: 9230443

3.Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth. Yingling JM, Das P, Savage C, Zhang M, Padgett RW, Wang XF. Proc. Natl. Acad. Sci. U.S.A. 93, 8940-4, (1996). View articlePMID: 8799132

4.Transforming growth factor-{beta}-inducible phosphorylation of Smad3. Wang G, Matsuura I, He D, Liu F. J Biol Chem 284, 9663-73, (2009). PMID: 19218245

5.Drosophila Nemo antagonizes BMP signaling by phosphorylation of Mad and inhibition of its nuclear accumulation. Zeng YA, Rahnama M, Wang S, Sosu-Sedzorme W, Verheyen EM. Development 134, 2061-71, (2007). PMID: 17507407

6.Relationship between the DNA binding domains of SMAD and NFI/CTF transcription factors defines a new superfamily of genes. Stefancsik R, Sarkar S. DNA Seq. 14, 233-9, (2003). View articlePMID: 14631647

GO terms

molecular function

  • None

cellular component

  • None

Cross References

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