| ATN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ATN1, B37, D12S755E, DRPLA, HRS, NOD, atrophin 1, CHEDDA | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607462; MGI: 104725; HomoloGene: 1461; GeneCards: ATN1; OMA:ATN1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Atrophin-1 is a protein that in humans is encoded by the ATN1 gene.[5] The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat.[6] The function of Atrophin-1 has not yet been determined.[7] There is evidence provided by studies of Atrophin-1 in animals to suggest it acts as a transcriptional co-repressor.[7] Atrophin-1 can be found in the nuclear and cytoplasmic compartments of neurons.[7] It is expressed in nervous tissue.[8]
The function of Atrophin-1 has not been defined yet. It is widely hypothesized that Atrophin-1 functions as a transcriptional co-repressor.[9] A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins.[9]
The ATN1 gene has a segment of DNA called the CAG trinucleotide repeat.[9] It is made up of cytosine, adenine, and guanine.[9] The number of CAG repeats in the ATN1 gene in a healthy person will range from six to thirty-five repeats.[9] CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1.[10] Studies have supported the idea that mutated Atrophin-1 gathers in neurons and disrupts cell function.[11] The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES).[11] 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.[11] This can lead to an increase in cellular toxicity.[11]
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.[5] The disorder is related to the expansion of a trinucleotide repeat within this gene.[5] In patients with DRPLA, truncated ATN1 has been observed forming intranuclear aggregates that cause cell death.[11] The symptoms of this disorder can be credited to the significant reduction of brain and spinal tissue observed in those afflicted with DRPLA.[12] There are both juvenile-onset and late adult-onset variants of DRPLA, which show differing degrees of severity of specific symptoms.[12]
ATN1 has been shown to interact with:
