InterPro domain: IPR000770

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 100kDa) [ 1 ], NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory Element Binding) proteins [ 2 ] 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 [ 3 , 4 ].

The resolution of the 3D structure of the SAND domain from Sp100b has revealed that it consists of a novel alpha/beta fold. The SAND domain adopts a compact fold consisting of a strongly twisted, five-stranded antiparallel beta-sheet with four alpha-helices packing against one side of the beta-sheet. The opposite side of the beta-sheet is solvent exposed. The beta-sheet and alpha-helical parts of the structure form two distinct regions.Multiple hydrophobic residues pack between these regions to form a structural core. A conserved KDWK sequence motif is found within the alpha-helical, positively charged surface patch. The DNA binding surface has been mapped to the alpha-helical region encompassing the KDWK motif [ 5 ].

1. Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc Natl Acad Sci U S A 95, 7316-21
2. Properties of the glucocorticoid modulatory element binding proteins GMEB-1 and -2: potential new modifiers of glucocorticoid receptor transactivation and members of the family of KDWK proteins. Mol. Endocrinol. 14, 1010-27
3. The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. Trends Biochem. Sci. 23, 242-4
4. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat. Struct. Biol. 8, 626-33