May play a role in microtubule-mediated transport or vesicle function.
Expressed in the brain cortex (at protein level). Widely expressed with the highest level of expression in the brain (nerve fibers, varicosities, and nerve endings). In the brain, the regions where it can be mainly found are the cerebellar cortex, the neocortex, the striatum, and the hippocampal formation.
Involvement in disease
Defects in HTT are the cause of Huntington disease (HD) [MIM:143100]. HD is an autosomal dominant neurodegenerative disorder characterized by involuntary movements (chorea), general motor impairment, psychiatric disorders and dementia. Onset of the disease occurs usually in the third or fourth decade of life and symptoms progressively worsen leading to death in 10 to 20 years. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. HD affects 1 in 10,000 individuals of European origin. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen (striatum).
Belongs to the huntingtin family. Contains 10 HEAT repeats.
The N-terminal Gln-rich and Pro-rich domain has great conformational flexibility and is likely to exist in a fluctuating equilibrium of alpha-helical, random coil, and extended conformations.
Cleaved by apopain downstream of the polyglutamine stretch. The resulting N-terminal fragment is cytotoxic and provokes apoptosis. Forms with expanded polyglutamine expansion are specifically ubiquitinated by SYVN1, which promotes their proteasomal degradation.
Cytoplasm. Nucleus. The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington's disease neurons.
Western blot - Anti-Huntingtin (phospho S434) antibody (ab155931)
All lanes : Anti-Huntingtin (phospho S434) antibody (ab155931) at 1/500 dilution
Lane 1 : Lysate of 293T transfected with Huntingtin Lane 2 : Lysate of 293T transfected with Huntingtin and treated with PPI inhibitor Lane 3 : Lysate of 293T transfected with Huntingtin and treated with PPI inhibitor and CDK5
Secondary All lanes : Goat anti-rabbit HRP conjugated antibody at 1/30000 dilution