Short name: Huntingtin
Overlapping homologous superfamilies
- Huntingtin family (IPR028426)
- Huntingtin (IPR000091)
Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerative disorder characterised by motor impairment, involuntary movements (chorea), psychiatric disorders and dementia [PMID: 7647794]. The disease results from the expansion of a polyglutamine-encoding CAG repeat in a gene of unknown function. Moderate expansion of glutamine-coding CAG repeats has been found in other neurological diseases (e.g. spinobulbar muscular atrophy and Machado-Joseph disease), in all of which the pathological mechanism linked to the expansion of the polyglutamine tract in the protein remains a mystery.
The HD transcript is highly conserved, significant differences, as already noted, occurring in the N-terminal Gln-repeat region. Huntingtin normally contains 10-35 repeats, but shows 36-120 repeats in the disease form. Migration differences between normal and mutated huntingtin in a denaturing polyacrylamide gel suggest that the poly-Gln stretch disrupts the protein conformation. This finding is consistent with the observation that Gln repeats may form tightly-linked beta-sheets that could act as polar zippers [PMID: 8202492]. It has been shown that neuronal inclusions of patients with Huntington's disease contains a broad range of N-terminal fragments of expanded huntingtin and insoluble polymers [PMID: 16181417]. The polymerisation of the monomeric huntingtin bearing a polyglutamine expansion is selectively produced by transglutaminase [PMID: 16181417, PMID: 9660943].
- PR00375 (HUNTINGTIN)