{PDOC50864} {PS50864; SAND} {BEGIN} *********************** * 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 ), the PHD finger (see ) 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 alpha/beta fold (see ). 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 [2]. The profile we developed covers the entire SAND domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: July 2002 / First entry. [ 1] Gibson T.J., Ramu C., Gemuend C., Aasland R. "The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor." Trends Biochem. Sci. 23:242-244(1998). PubMed=9697411 [ 2] Bottomley M.J., Collard M.W., Huggenvik J.I., Liu Z., Gibson T.J., Sattler M. "The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation." Nat. Struct. Biol. 8:626-633(2001). PubMed=11427895; DOI=10.1038/89675 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}