Pathways & interactions
SAND-like domain superfamily (IPR010919)
Short name: SAND-like_dom_sf
- SAND domain (IPR000770)
- c-SKI SMAD4-binding domain (IPR014890)
- Transcription regulator SKI/SnoN (IPR023216)
- Glucocorticoid modulatory element-binding protein 1/2 (IPR024830)
- Ski-related oncogene Sno (IPR028373)
- SKI family transcriptional corepressor 2 (IPR028376)
- Ski oncogene (IPR028760)
- Ski family transcriptional corepressor 1 (IPR028762)
The SAND domain (named after Sp100, AIRE-1, NucP41/75, DEAF-1) is a conserved ~80 residue region found in a number of nuclear proteins, many of which function in chromatin-dependent transcriptional control. These include proteins linked to various human diseases, such as the Sp100 (Speckled protein 100 kDa), NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory Element Binding) proteins and AIRE-1 (Autoimmune regulator 1) proteins.
Proteins containing the SAND domain have a modular structure; the SAND domain can be associated with a number of other modules, including the bromodomain, the PHD finger and the MYND finger. Because no SAND domain has been found in yeast, it is thought that the SAND domain could be restricted to animal phyla. Many SAND domain-containing proteins, including NUDR, DEAF-1 (Deformed epidermal autoregulatory factor-1) and GMEB, have been shown to bind DNA sequences specifically. The SAND domain has been proposed to mediate the DNA binding activity of these proteins [PMID: 9697411, PMID: 11427895]. Structurally, the SAND domain consists of a novel alpha/beta fold, which has a core of three short helices packed against a barrel-like beta-sheet; it is structurally similar to the SH3-like fold.
Other proteins display domains that are structurally similar to the SAND domain. One such example is the SMAD4-binding domain of the oncoprotein Ski, which is stabilised by a bound zinc atom, and resembles a SAND domain, in which the corresponding I loop is responsible for DNA binding. Ski is able to disrupt the formation of a functional complex between the Co- and R-SMADs, leading to the repression of TGF-beta, Activin and BMP responses, resulting in the repression of TGF-signalling [PMID: 12419246].