SBDS

Ribosome maturation protein SBDS is a is_associated_with::protein that in humans is encoded by the SBDS is_associated_with::gene. An alternative transcript has been described, but its biological nature has not been determined. This gene has a closely linked pseudogene that is distally located. This gene encodes a member of a highly conserved protein family that exists from archaea to vertebrates and plants.

Function
The encoded protein may function in RNA metabolism. The precise function of the SBDS protein is not known but it appears to play an important role in is_associated_with::ribosome function or assembly. Knockdown of SBDS expression results in increased is_associated_with::apoptosis in is_associated_with::erythroid cells undergoing differentiation due to elevated ROS levels. Hence SBDS is critical for normal is_associated_with::erythropoiesis.

This family is highly conserved in species ranging from archaea to vertebrates and plants. The family contains several Shwachman-Bodian-Diamond syndrome (SBDS) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. Members of this family play a role in RNA metabolism.

A number of uncharacterised hydrophilic proteins of about 30 kDa share regions of similarity. These include,


 * Mouse protein 22A3.
 * is_associated_with::Saccharomyces cerevisiae chromosome XII hypothetical protein YLR022c.
 * is_associated_with::Caenorhabditis elegans hypothetical protein W06E11.4.
 * is_associated_with::Methanococcus jannaschii hypothetical protein MJ0592.

This particular protein sequence is highly conserved in is_associated_with::species ranging from is_associated_with::archaea to is_associated_with::vertebrates and is_associated_with::plants.

Structure
The SBDS protein contains three domains, an is_associated_with::N-terminal conserved FYSH domain, central helical domain and is_associated_with::C-terminal domain containing an RNA-binding motif.

Function
This protein domain appears to be very important, since mutations in this domain are usually the cause of Shwachman-Bodian-Diamond syndrome. It shares distant structural and sequence homology to a protein named YHR087W found in the yeast is_associated_with::Saccharomyces cerevisiae. The protein YHR087W is involved in RNA metabolism, so it is probable that the SBDS N-terminal domain has the same function.

Structure
The N-terminal domains contains a novel mixed alphabeta fold, four beta-strands, and four alpha-helices arranged as a three beta stranded anti-parallel-sheet.

Function
The function of this protein domain has been difficult to elucidate. It is possible that it has a role in binding to is_associated_with::DNA or is_associated_with::RNA. Protein binding to form a protein complex is also another possibility. It has been difficult to infer the function from the structure since this particular domain structure is found in is_associated_with::archea.

Structure
This domain contains a very common structure, the winged is_associated_with::helix-turn-helix.

SBDS C-terminal domain
In is_associated_with::molecular biology, the SBDS is_associated_with::C-terminal is_associated_with::protein domain is highly conserved in is_associated_with::species ranging from is_associated_with::archaea to is_associated_with::vertebrates and is_associated_with::plants.

Function
Members of this family are thought to play a role in RNA metabolism. However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.

Structure
The structure of the C-terminal domain contains a ferredoxin-like fold This structure has a four-stranded is_associated_with::beta-sheet with two helices on one side.

Clinical significance
Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome. The two most common mutations associated with this syndrome are at positions 183–184 (TA→CT) resulting in a premature stop-codon (K62X) and a frameshift mutation at position 258 (2T→C) resulting in a stopcodon (C84fsX3).