ATXN1 phospho S776
Domain
The AXH domain is required for interaction with CIC.
Function
Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Binds RNA in vitro. May be involved in RNA metabolism (PubMed:21475249). In concert with CIC and ATXN1L, involved in brain development (By similarity).
Involvement in disease
Spinocerebellar ataxia 1
SCA1
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
None
The disease is caused by variants affecting the gene represented in this entry. The disease is caused by expansion of the polyglutamine tract to about 40-83 repeats, causing accumulation in neurons and exerting toxicity.
Post-translational modifications
Ubiquitinated by UBE3A, leading to its degradation by the proteasome. The presence of expanded poly-Gln repeats in spinocerebellar ataxia 1 (SCA1) patients impairs ubiquitination and degradation, leading to accumulation of ATXN1 in neurons and subsequent toxicity.
Phosphorylation at Ser-775 increases the pathogenicity of proteins with an expanded polyglutamine tract.
Sumoylation is dependent on nuclear localization and phosphorylation at Ser-775. It is reduced in the presence of an expanded polyglutamine tract.
Sequence Similarities
Belongs to the ATXN1 family.
Tissue Specificity
Widely expressed throughout the body.
Cellular localization
- Cytoplasm
- Nucleus
- Colocalizes with USP7 in the nucleus.
Alternative names
ATX1, SCA1, ATXN1, Ataxin-1, Spinocerebellar ataxia type 1 protein