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4  structures 96  species 0  interactions 491  sequences 30  architectures

Family: SAND (PF01342)

Summary: SAND domain

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This is the Wikipedia entry entitled "SAND DNA-binding protein domain". More...

SAND DNA-binding protein domain Edit Wikipedia article

SAND
PDB 1ufn EBI.jpg
Solution structure of the SAND domain of the putative nuclear protein homolog (5830484a20rik)
Identifiers
Symbol SAND
Pfam PF01342
InterPro IPR000770
SCOP 1h5p
SUPERFAMILY 1h5p

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.

Function

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.[1] 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.[2]

Structure

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.[2] 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.[2]

Conservation

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.[2][3]

Some proteins with SAND domain

References

  1. ^ Wojciak JM, Clubb RT (2001). "Finding the function buried in SAND.". Nat Struct Biol 8 (7): 568–70. doi:10.1038/89582. PMID 11427878. 
  2. ^ a b c d 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. 
  3. ^ Gibson TJ, Ramu C, Gemünd 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. 

This article incorporates text from the public domain Pfam and InterPro IPR000770

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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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 [2]. 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 [3].

Literature references

  1. 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

  2. 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

  3. 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].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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(51)
RP35
(98)
RP55
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RP75
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  Seed
(27)
Full
(491)
Representative proteomes NCBI
(486)
Meta
(2)
RP15
(51)
RP35
(98)
RP55
(148)
RP75
(249)
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  Seed
(27)
Full
(491)
Representative proteomes NCBI
(486)
Meta
(2)
RP15
(51)
RP35
(98)
RP55
(148)
RP75
(249)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Curation and family details

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Curation View help on the curation process

Seed source: [1]
Previous IDs: none
Type: Family
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 82
Family (HMM) version: 16
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Species distribution

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Structures

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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