molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and phys ...

, the

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist o ...

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 Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...

-dependent transcriptional control. It is found solely in

eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...

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. Here, the conserved positively charged

residues Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are appli ...

in the SAND domains suggest the existence of negatively charged ligands. DNA is a negatively charged molecule due to the

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

found in its backbone. Henceforth, this suggests that the SAND domain is the DNA-binding region of DEAF-1.

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 strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

s. This structure is made up of a five-stranded antiparallel

beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

with four

alpha-helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

. Further, the SAND domain is thought to have a modular structure; it can be associated with the

bromodomain A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transduci ...

, the

PHD finger PHD or PhD may refer to: * Doctor of Philosophy (PhD), an academic qualification Entertainment * '' PhD: Phantasy Degree'', a Korean comic series * ''Piled Higher and Deeper'', a web comic * Ph.D. (band), a 1980s British group **Ph.D. (Ph.D. albu ...

and the MYND finger.

Conservation

This protein domain has a conserved region of around 80

. 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)

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s and AIRE-1 (Autoimmune regulator 1)

Some proteins with SAND domain

Sp100 nuclear antigen Sp100 nuclear antigen is an interferon stimulated antigen found in the cell nuclei of many human and higher animal cells. Autoantibodies directed against Sp100 are often found in patients with primary biliary cirrhosis. Histologically Sp100 'dots' ...

AIRE Aire may refer to: Music * ''Aire'' (Yuri album), 1987 * ''Aire'' (Pablo Ruiz album), 1997 *''Aire (Versión Día)'', an album by Jesse & Joy Places *Aire-sur-la-Lys, a town in the Pas-de-Calais département in France * Aire-la-Ville, a munici ...

* DEAF1 *

GMEB1 Glucocorticoid modulatory element-binding protein 1 is a protein that in humans is encoded by the ''GMEB1'' gene. Function This gene is a member of KDWK gene family. The product of this gene associates with GMEB2 protein, and the complex is es ...

GMEB2 Glucocorticoid modulatory element-binding protein 2 is a protein that in humans is encoded by the ''GMEB2'' gene. This gene is a member of KDWK gene family. The product of this gene associates with GMEB1 protein, and the complex is essential fo ...

References

{{InterPro content, IPR000770 Protein families