Ataxin-7 is a nuclear protein encoded by the [ATXN7 gene](/proteins/atxn7-protein) that functions as a component of the SPT3/SAGA/SLIK histone acetyltransferase (HAT) complex. In its wild-type form, ataxin-7 is involved in transcriptional regulation through chromatin remodeling. However, pathogenic expansions of a polyglutamine (polyQ) tract in the N-terminal region cause [spinocerebellar ataxia type 7 (SCA7)](/diseases/spinocerebellar-ataxia-type-7), a progressive neurodegenerative disorder characterized by cerebellar degeneration, retinal dystrophy, and systemic multi-system involvement.
Ataxin-7 is a nuclear protein encoded by the [ATXN7 gene](/proteins/atxn7-protein) that functions as a component of the SPT3/SAGA/SLIK histone acetyltransferase (HAT) complex. In its wild-type form, ataxin-7 is involved in transcriptional regulation through chromatin remodeling. However, pathogenic expansions of a polyglutamine (polyQ) tract in the N-terminal region cause [spinocerebellar ataxia type 7 (SCA7)](/diseases/spinocerebellar-ataxia-type-7), a progressive neurodegenerative disorder characterized by cerebellar degeneration, retinal dystrophy, and systemic multi-system involvement.
Structure
Ataxin-7 is a 892-amino acid protein with the following domain organization:
Polyglutamine (polyQ) tract (aa ~10-90): Normal: 7-35 glutamines; Pathogenic: 36-306 glutamines. The polyQ expansion causes protein misfolding and aggregation
N-terminal region (aa 91-300): Contains the SCA7 disease domain and interaction sites
SAGA interaction domain (aa 300-500): Binds to SPT3, SPT8, and other SAGA complex subunits
C-terminal region (aa 501-892): Contains nuclear localization signals (NLS) and protein-protein interaction motifs
No crystal structures are available, but the AlphaFold model reveals the overall protein fold: [AlphaFold Entry O75376](https://alphafold.ebi.ac.uk/entry/O75376).
Normal Function
Under physiological conditions, ataxin-7 performs essential functions:
SAGA Complex Component
Ataxin-7 is a stable component of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) histone acetyltransferase complex, which regulates:
Gene transcription through histone H3/H4 acetylation
Chromatin remodeling
RNA polymerase II recruitment
Transcriptional Regulation
The SAGA-ataxin-7 module is particularly important for:
Expression of photoreceptor-specific genes
Cerebellar neuron gene regulation
Cellular stress response genes
Protein-Protein Interactions
Ataxin-7 interacts with:
SAGA complex subunits (SPT3, SPT8, SPT20, GCN5)
Transcription factors
Nuclear co-repressors
Role in Neurodegeneration
Spinocerebellar Ataxia Type 7 (SCA7)
[SCA7](/diseases/spinocerebellar-ataxia-type-7) is an autosomal dominant disorder caused by CAG trinucleotide repeat expansions in the ATXN7 gene. The expanded polyQ tract leads to:
Pathogenic Mechanisms
Protein Aggregation
Mutant ataxin-7 forms insoluble nuclear aggregates
Aggregates sequester normal protein and transcription factors
Disrupts nuclear architecture and proteostasis
Transcriptional Dysregulation
Impaired SAGA complex function
Decreased histone acetylation
Downregulation of essential neuronal genes
Specific vulnerability of photoreceptors and cerebellar Purkinje cells