PROSITE documentation PDOC50864

{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 <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 alpha/beta fold (see <PDB:1H5P>). 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}