PROSITE documentation PDOC50864

SAND domain profile

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 (see <PDOC00550>), the PHD finger (see <PDOC50016>) 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 sequence-specifically. The SAND domain has been proposed to mediate the DNA binding activity of these proteins [1,2].

The resolution of the 3D structure of the SAND domain from Sp100b has revealed that it consists of a novel α/β fold (see <PDB:1H5P>). The SAND domain adopts a compact fold consisting of a strongly twisted, five-stranded antiparallel β-sheet with four α-helices packing against one side of the β-sheet. The opposite side of the β-sheet is solvent exposed. The β-sheet and α-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 α-helical, positively charged surface patch. The DNA binding surface has been mapped to the α-helical region encompassing the KDWK motif [2].

The profile we developed covers the entire SAND domain.