Summary: SAND domain

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

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SAND DNA-binding protein domain Edit Wikipedia article

SAND

solution structure of the sand domain of the putative nuclear protein homolog (5830484a20rik)

Identifiers

Symbol

SAND

1h5p / SCOPe / SUPFAM

Available protein structures:
Pfam Â	structures / ECOD Â
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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.^[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. 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]

References

^ Gibson TJ, Ramu C, GemÃƒÂ¼nd C, Aasland R (1998). "The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor". Trends Biochem. Sci. 23 (7): 242â€“4. PMIDÂ 9697411. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ ^a ^b 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): 626â€“33. doi:10.1038/89675. PMIDÂ 11427895. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

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.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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

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

SCOP:

1h5p

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 100kDa) [ PUBMED:9636146 ], NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory Element Binding) proteins [ PUBMED:10894151 ] 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

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)

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

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (58)	Full (3059)	Representative proteomes				UniProt (4860)
	Seed (58)	Full (3059)	RP15 (311)	RP35 (912)	RP55 (2128)	RP75 (3111)	UniProt (4860)
Jalview	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (58)	Full (3059)	Representative proteomes				UniProt (4860)
	Seed (58)	Full (3059)	RP15 (311)	RP35 (912)	RP55 (2128)	RP75 (3111)	UniProt (4860)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (58)	Full (3059)	Representative proteomes				UniProt (4860)
	Seed (58)	Full (3059)	RP15 (311)	RP35 (912)	RP55 (2128)	RP75 (3111)	UniProt (4860)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

[1]

Previous IDs:

none

Type:

Family

Sequence Ontology:

SO:0100021

Author:

Christensen J, Bateman A

Number in seed:

58

Number in full:

3059

Average length of the domain:

74.5 aa

Average identity of full alignment:

36 %

Average coverage of the sequence by the domain:

13.33 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	22.0	22.0
Trusted cut-off	22.0	22.1
Noise cut-off	21.9	21.9

Model length:

77

Family (HMM) version:

24

Download:

download the raw HMM for this family

Species distribution

Sunburst
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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Align selected sequences to HMM

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

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 sequence.

Loading structure mapping...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein	Predicted structure	External Information
A0A044SY86	View 3D Structure	Click here
A0A0G2JZU7	View 3D Structure	Click here
A0A0K0DYD7	View 3D Structure	Click here
A0A0N4UBC2	View 3D Structure	Click here
A0A0R4ICN1	View 3D Structure	Click here
A0A0R4IHB7	View 3D Structure	Click here
A0A0R4IMH4	View 3D Structure	Click here
A0A0R4ITE9	View 3D Structure	Click here
A0A1P6BSD2	View 3D Structure	Click here
A0A2R8QHZ5	View 3D Structure	Click here
A0A2R8QK64	View 3D Structure	Click here
B3DHN2	View 3D Structure	Click here
E7F6B2	View 3D Structure	Click here
E7F805	View 3D Structure	Click here
E9QCL9	View 3D Structure	Click here
F1QN94	View 3D Structure	Click here
F1R6N2	View 3D Structure	Click here
J9ET50	View 3D Structure	Click here
O17208	View 3D Structure	Click here
O35892	View 3D Structure	Click here
O43918	View 3D Structure	Click here
O75398	View 3D Structure	Click here
O77562	View 3D Structure	Click here
O88450	View 3D Structure	Click here
O88873	View 3D Structure	Click here
P23497	View 3D Structure	Click here
P58929	View 3D Structure	Click here
Q13342	View 3D Structure	Click here
Q18171	View 3D Structure	Click here
Q18624	View 3D Structure	Click here
Q24180	View 3D Structure	Click here
Q2HJ87	View 3D Structure	Click here
Q3KRF1	View 3D Structure	Click here
Q6NSQ5	View 3D Structure	Click here
Q8BVK9	View 3D Structure	Click here
Q93779	View 3D Structure	Click here
Q9H930	View 3D Structure	Click here
Q9HB58	View 3D Structure	Click here
Q9JL60	View 3D Structure	Click here
Q9N1Q6	View 3D Structure	Click here

Showing 40 matches

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Family: SAND (PF01342)

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