This entry represents a conserved region approximately 250 residues long located on eukaryotic ataxin-2 [ (PUBMED:16115810) ]. Ataxin-2 is a protein of unknown function, within which expansion of a polyglutamine tract (due to expansion of unstable CAG repeats in the coding region of the SCA2 gene) causes spinocerebellar ataxia type 2 (SCA2), a late-onset neurodegenerative disorder [ (PUBMED:9339681) ]. The expanded polyglutamine repeat in ataxin-2 causes disruption of the normal morphology of the Golgi complex and increased incidence of cell death [ (PUBMED:12812977) ]. Ataxin-2 is predicted to consist of mostly non-globular domains [ (PUBMED:9462862) ].
Family alignment:
There are 2461 LsmAD domains in 2455 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing LsmAD domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with LsmAD domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing LsmAD domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Ataxin-2 and huntingtin interact with endophilin-A complexes to function inplastin-associated pathways.
Hum Mol Genet. 2005; 14: 2893-909
Display abstract
Spinocerebellar ataxia type 2 is an inherited neurodegenerative disorder that is caused by an expanded trinucleotide repeat in the SCA2 gene, encoding apolyglutamine stretch in the gene product ataxin-2. Although evidence has beenprovided that ataxin-2 is involved in RNA metabolism, the physiological function of ataxin-2 remains unclear. Here, we demonstrate that ataxin-2 interacts withtwo members of the endophilin family, endophilin-A1 and endophilin-A3. Toelucidate the physiological implications of these interactions, we exploitedyeast as a model system and discovered that expression of ataxin-2 as well asboth endophilin proteins is toxic for yeast lacking the SAC6 gene productfimbrin, a protein involved in actin filament organization and endocytoticprocesses. Intriguingly, expression of huntingtin, another polyglutamine protein interacting with endophilin-A3, was also toxic in Deltasac6 yeast. These effects can be suppressed by simultaneous expression of one of the two human fimbrinorthologs, L- or T-plastin. Moreover, we have discovered that ataxin-2 associateswith L- and T-plastin and that overexpression of ataxin-2 leads to accumulationof T-plastin in mammalian cells. Thus, our findings suggest an interplay between ataxin-2, endophilin proteins and huntingtin in plastin-associated cellularpathways.
Links (links to other resources describing this domain)
