InterPro domain: IPR036786

Proteins containing this domain are highly conserved in species ranging from archaea to vertebrates and plants [ 1 ], including several Shwachman-Bodian-Diamond syndrome (SBDS, OMIM 260400) 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. It is characterised by bone marrow failure and leukemia predisposition. Members of this superfamily play a role in RNA metabolism [ 2 , 3 ]. In yeast Sdo1 is involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition [ 4 ].

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

• Mouse protein 22A3.
• Saccharomyces cerevisiae chromosome XII hypothetical protein YLR022c.
• Caenorhabditis elegans hypothetical protein W06E11.4.
• Methanocaldococcus jannaschii (Methanococcus jannaschii) hypothetical protein MJ0592.

1. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat. Genet. 33, 97-101
2. Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome. J. Biol. Chem. 280, 19221-9
3. The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism. J. Biol. Chem. 280, 19213-20
4. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat. Genet. 39, 486-95