Ataxin-2 is a RNA-binding protein involved in RNA metabolism, stress granule formation, and translational control. Associated with spinocerebellar ataxia type 2, Parkinson's disease, and ALS.
Atxn2 — Ataxin 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Property |
Value |
| Gene Symbol |
ATXN2 |
| Full Name |
Ataxin-2 |
| Chr Location |
12q24.1 |
| NCBI Gene ID |
6313 |
| OMIM ID |
601431 |
| Ensembl ID |
ENSG00000204852 |
| UniProt ID |
Q99700 |
| Encoded Protein |
Ataxin-2 |
| Associated Diseases |
Spinocerebellar ataxia type 2 (SCA2), Parkinson's disease, ALS, diabetes |
ATXN2 encodes ataxin-2, a large RNA-binding protein with multiple domains including an RNA-binding motif (Lsm, PAM2) and a polyglutamine (polyQ) tract. Ataxin-2 is involved in RNA metabolism, stress granule formation, and translational control.
Key normal physiological functions include:
- RNA metabolism - Binds RNA and regulates RNA processing
- Stress granules - Component of stress granule complexes
- Translation control - Regulates translation initiation and mRNA stability
- Insulin signaling - Involved in pancreatic beta-cell function
- Synaptic function - Regulates neurotransmitter release
- Autophagy - Involved in autophagic protein clearance
The protein structure includes:
- N-terminal domain - PAM2 motif for PABP binding
- Central region - Polyglutamine tract (normal ~22-33, expanded in disease)
- Lsm domain - RNA binding
- C-terminal domain - Protein interactions
SCA2 is caused by CAG repeat expansion in ATXN2:
- Repeat expansion - >32 CAG repeats cause disease
- Phenotype - Progressive ataxia, slow saccades, peripheral neuropathy
- Mechanism - Toxic gain-of-function from expanded polyQ
- Neurodegeneration - Purkinje cell loss, brainstem involvement
- ATXN2 intermediate expansions increase PD risk
- Ataxin-2 inclusions in PD brains
- RNA metabolism dysregulation in PD
- ATXN2 expansions increase ALS risk
- Ataxin-2 positive inclusions in ALS motor neurons
- Interaction with TDP-43 pathology
- ATXN2 variants associated with diabetes risk
- Role in pancreatic beta-cell function
Ataxin-2 is widely expressed in the brain:
- Highest expression: Cerebellum (Purkinje cells), cortex, brainstem, spinal cord
- Moderate expression: Most neural tissues
- Cellular localization: Cytoplasm, stress granules
- Cell types: Neurons, pancreatic beta cells
The Allen Brain Atlas shows high ATXN2 expression in:
- Cerebellar Purkinje cells
- Brainstem motor neurons
- Spinal cord motor neurons
- Cortical pyramidal neurons
- Pulst et al., SCA2 identification (1996)
- Elden et al., ATXN2 expansions in ALS (2010)
- Bhattacharjee et al., ATXN2 in RNA metabolism (2011)
The study of Atxn2 — Ataxin 2 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Pulst et al., SCA2 identification (1996)
- Elden et al., ATXN2 expansions in ALS (2010)
- Bhattacharjee et ATXN2 in RNA metabolism (2011)
- Last et al., Ataxin-2 function and disease (2020)
- Sato et al., ATXN2 in Parkinson's disease (2019)
- Gispert-Sanchez et al., ATXN2 and RNA granules (2015)
- Nonis et al., ATXN2 in diabetes (2022)
- Kumar et al., ATXN2 therapeutic targeting (2021)