Atrophin 1

Function

The function of Atrophin-1 has not been defined yet. It is widely hypothesized that Atrophin-1 functions as a transcriptional co-repressor. A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins.

Clinical significance

The ATN1 gene has a segment of DNA called the CAG trinucleotide repeat. It is made up of cytosine, adenine, and guanine. The number of CAG repeats in the ATN1 gene in a healthy person will range from six to thirty-five repeats. CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1. Studies have supported the idea that mutated Atrophin-1 gathers in neurons and disrupts cell function. The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES). It has been shown that a mutation of the NES in ATN1 can change where ATN1 localizes, and can cause aggregation to occur in the nucleus. This can lead to an increase in cellular toxicity.

Mutations in ATN1 are associated with a form of trinucleotide repeat disorder known as "dentatorubral-pallidoluysian atrophy" or "dentatorubropallidoluysian atrophy". Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion of a trinucleotide repeat within this gene. ** **In patients with DRPLA, truncated ATN1 has been observed forming intranuclear aggregates that cause cell death. The symptoms of this disorder can be credited to the significant reduction of brain and spinal tissue observed in those afflicted with DRPLA. There are both juvenile-onset and late adult-onset variants of DRPLA, which show differing degrees of severity of specific symptoms.

Interactions

ATN1 has been shown to interact with:

• BAIAP2,
• MAGI1,
• MAGI2,
• RERE, and
• WWP2.

References

References

1. "ATN1 atrophin 1 [Homo sapiens (human)] - Gene - NCBI".
2. "Entrez Gene: ATN1 atrophin 1".
3. (September 2000). "Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription". The Journal of Cell Biology.
4. (February 2009). "Atrophins' emerging roles in development and neurodegenerative disease". Cellular and Molecular Life Sciences.
5. "ATN1 gene". Genetics Home Reference.
6. (February 2007). "Functional architecture of atrophins". The Journal of Biological Chemistry.
7. (April 2011). "Pathological accumulation of atrophin-1 in dentatorubralpallidoluysian atrophy". International Journal of Clinical and Experimental Pathology.
8. "Dentatorubral-Pallidoluysian Atrophy, DRPLA".
9. (June 1999). "Dentatorubral-pallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate". Human Molecular Genetics.
10. (June 1998). "Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins". Molecular and Cellular Neurosciences.
11. (May 2000). "Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine". Human Molecular Genetics.