SAND DNA-binding protein domain

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.

SAND
Solution structure of the SAND domain of the putative nuclear protein homolog (5830484a20rik)
Identifiers
SymbolSAND
PfamPF01342
InterProIPR000770
SCOP21h5p / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Function

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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

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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

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This protein domain has a conserved region of around 80 residues. 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

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References

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  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. S2CID 32113775.
  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. S2CID 6642673.
  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