Summary: SAND domain
This is the Wikipedia entry entitled "SAND DNA-binding protein domain". More...
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SAND DNA-binding protein domain Edit Wikipedia article
Solution structure of the SAND domain of the putative nuclear protein homolog (5830484a20rik)
In molecular biology, the protein domain SAND is named after a range of proteins in the protein family: Sp100, AIRE-1, NucP41/75, DEAF-1. It is localised in the cell nucleus and has an important function in chromatin-dependent transcriptional control. It is found solely in eukaryotes.
The precise function of the protein domain SAND remains to be determined. Nevertheless, it is thought to be a DNA binding domain despite its beta structure. This function can be inferred by studying the DEAF-1 transcription factor. Here, the conserved positively charged residues in the SAND domains suggest the existence of negatively charged ligands. DNA is a negatively charged molecule due to the phosphate found in its backbone. Henceforth, this suggests that the SAND domain is the DNA-binding region of DEAF-1.
The structure of this protein domain contains a globular fold. It is thought to have an alpha/beta secondary structure that consists of five beta strands. This structure is made up of a five-stranded antiparallel beta-sheet with four alpha-helices. Further, the SAND domain is thought to have a modular structure; it can be associated with the bromodomain, the PHD finger and the MYND finger.
This protein domain has a conserved region of around 80 residuea. Mutations in this region lead to various human diseases, particularly in these proteins: Sp100 (Speckled protein 100 kDa), NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory Element Binding) proteins and AIRE-1 (Autoimmune regulator 1) proteins.
Some proteins with SAND domain
- Wojciak JM, Clubb RT (2001). "Finding the function buried in SAND.". Nat Struct Biol 8 (7): 568–70. doi:10.1038/89582. PMID 11427878.
- Bottomley MJ, Collard MW, Huggenvik JI, Liu Z, Gibson TJ, Sattler M (2001). "The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation.". Nat Struct Biol 8 (7): 626–33. doi:10.1038/89675. PMID 11427895.
- Gibson TJ, Ramu C, GemÃ¼nd C, Aasland R (July 1998). "The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor". Trends Biochem. Sci. 23 (7): 242–4. doi:10.1016/s0968-0004(98)01231-6. PMID 9697411.
SAND domain Provide feedback
The DNA binding activity of two proteins has been mapped to the SAND domain. The conserved KDWK motif is necessary for DNA binding, and it appears to be important for dimerisation . This region is also found in the putative transcription factor RegA from the multicellular green alga Volvox cateri. This region of RegA is known as the VARL domain .
Gibson TJ, Ramu C, Gemund C, Aasland R; , Trends Biochem Sci 1998;23:242-244.: The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. PUBMED:9697411 EPMC:9697411
Bottomley MJ, Collard MW, Huggenvik JI, Liu Z, Gibson TJ, Sattler M; , Nat Struct Biol 2001;8:626-633.: The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. PUBMED:11427895 EPMC:11427895
Duncan L, Nishii I, Harryman A, Buckley S, Howard A, Friedman NR, Miller SM; , J Mol Evol. 2007;65:1-11.: The VARL gene family and the evolutionary origins of the master cell-type regulatory gene, regA, in Volvox carteri. PUBMED:17646893 EPMC:17646893
External database links
This tab holds annotation information from the InterPro database.
InterPro entry 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 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 [PUBMED:9697411, PUBMED:11427895].
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 [PUBMED:11427895].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||DNA binding (GO:0003677)|
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Curation and family details
|Author:||Christensen J, Bateman A|
|Number in seed:||27|
|Number in full:||491|
|Average length of the domain:||78.20 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||13.91 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SAND domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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