• The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. (benthamscience.com)
  • It is widely hypothesized that Atrophin-1 functions as a transcriptional co-repressor. (wikipedia.org)
  • Mutant Huntingtin is the cause of the complex neurological metabolic alteration of Huntington's disease, resulting in both the loss of all the functions of normal Huntingtin and the genesis of abnormal interactions due to the presence of this mutation. (benthamscience.com)
  • Both patients and DRPLA transgenic mice have nuclear accumulation of atrophin-1, especially an approximately 120-kDa fragment, which appears to represent a cleavage product. (nih.gov)
  • Atrophin-1 is a protein that in humans is encoded by the ATN1 gene. (wikipedia.org)
  • The ATN1 gene has a segment of DNA called the CAG trinucleotide repeat. (wikipedia.org)
  • The number of CAG repeats in the ATN1 gene in a healthy person will range from six to thirty-five repeats. (wikipedia.org)
  • CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1. (wikipedia.org)
  • The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES). (wikipedia.org)
  • The diagnosis of DRPLA is established in a proband with suggestive clinical findings and a heterozygous pathogenic CAG trinucleotide expansion in ATN1 identified by molecular genetic testing . (nih.gov)
  • Once an abnormal CAG repeat expansion in ATN1 has been identified in an affected family member, prenatal and preimplantation genetic testing are possible. (nih.gov)
  • The atrophin-1 sequence contains a putative nuclear localization signal in the N terminus of the protein and a putative nuclear export signal in the C terminus. (nih.gov)
  • The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. (wikipedia.org)
  • One structural feature of htt that has been identified is the presence of HEAT repeats [ 20 ], which are sequences of ~40 amino acids that occur multiple times within a given protein and are found in a variety of proteins involved in intracellular transport and chromosomal segregation [ 21 ]. (biomedcentral.com)
  • The hunt for the HD gene involved an intense molecular genetics research effort by investigators cooperating around the globe. (biomedcentral.com)
  • A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins. (wikipedia.org)
  • The genetic defect responsible for the disease is expansion of a CAG repeat in the gene coding for the HD protein, huntingtin (htt). (biomedcentral.com)
  • Atrophin-1 can be found in the nuclear and cytoplasmic compartments of neurons. (wikipedia.org)
  • We have tested the hypothesis that endogenous localization signals are functional in atrophin-1, and that nuclear localization and proteolytic cleavage contribute to atrophin-1 cell toxicity. (nih.gov)
  • Studies have supported the idea that mutated Atrophin-1 gathers in neurons and disrupts cell function. (wikipedia.org)
  • The function of Atrophin-1 has not yet been determined. (wikipedia.org)