Atrophin 1

ATN1
Identifiers
Aliases	ATN1, B37, D12S755E, DRPLA, HRS, NOD, atrophin 1, CHEDDA
External IDs	OMIM: 607462; MGI: 104725; HomoloGene: 1461; GeneCards: ATN1; OMA:ATN1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)1 Band 12p13.31 Start 6,924,463 bp1 End 6,942,321 bp1
Gene location (Mouse) Chr. Chromosome 6 (mouse)2 Band 6 F2|6 59.17 cM Start 124,719,507 bp2 End 124,733,487 bp2
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum anterior pituitary left ovary right uterine tube right ovary right lobe of thyroid gland left lobe of thyroid gland body of uterus gastric mucosa canal of the cervix Top expressed in neural layer of retina primary visual cortex superior frontal gyrus genital tubercle dentate gyrus of hippocampal formation granule cell cerebellar cortex muscle of thigh lip ventricular zone tail of embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding transcription corepressor activity protein domain specific binding DNA binding Cellular component nuclear matrix perinuclear region of cytoplasm cell junction nucleoplasm cytoplasm nucleus Biological process neuron apoptotic process central nervous system development regulation of transcription, DNA-templated negative regulation of transcription by RNA polymerase II transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1822 13498 Ensembl ENSG00000111676 ENSMUSG00000004263 UniProt P54259 O35126 RefSeq (mRNA) NM_001940 NM_001007026 NM_007881 RefSeq (protein) NP_001007027 NP_001931 NP_031907 Location (UCSC) Chr 12: 6.92 – 6.94 Mb Chr 6: 124.72 – 124.73 Mb PubMed search 3 4
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:

• BAIAP2,¹³
• MAGI1,¹⁴
• MAGI2,¹⁴
• RERE,¹⁵ and
• WWP2.¹⁴