Atrophin-1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ATN1
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat.
The function of Atrophin-1 has not yet been determined.
There is evidence provided by studies of Atrophin-1 in animals to suggest it acts as a transcriptional
co-repressor.
Atrophin-1 can be found in the nuclear and cytoplasmic compartments of neurons.
It is expressed in
nervous tissue
Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain ...
.
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 protein
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, becau ...
s.
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 biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
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
A nuclear export signal (NES) is a short target peptide containing 4 hydrophobic residues in a protein that targets it for export from the cell nucleus to the cytoplasm through the nuclear pore complex using nuclear transport. It has the opposit ...
(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
In genetics, trinucleotide repeat disorders, a subset of microsatellite expansion diseases (also known as repeat expansion disorders), are a set of over 30 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which ...
known as "
dentatorubral-pallidoluysian atrophy" or "dentatorubropallidoluysian atrophy". Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare
neurodegenerative
A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
disorder characterized by
cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.
Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...
,
myoclonic epilepsy,
choreoathetosis, and
dementia
Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
.
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
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 is an enzyme that in humans is encoded by the ''MAGI1'' gene.
Function
The protein encoded by this gene is a member of the membrane-associated guanylate kinase homo ...
,
[
* MAGI2,]WWP2
NEDD4-like E3 ubiquitin-protein ligase WWP2 also known as atrophin-1-interacting protein 2 (AIP2) or WW domain-containing protein 2 (WWP2) is an enzyme that in humans is encoded by the ''WWP2'' gene.
Function
This gene encodes a member of the ...
.[
]
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on DRPLA
*
* {{UCSC gene info, ATN1
Transcription coregulators