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Huntingtin is a protein, present in human cells. An abnormal form of the protein is associated with Huntington's Disease.

Contents

Introduction

Function

Abnormal huntingtin

History

References

External links

Introduction

'Huntingtin' (Htt) is the protein coded by the HD gene. It is variable in its structure. There are many polymorphisms of the HD gene which can lead to variable numbers of glutamine residues present. In its wild-type (normal) form, it contains 6-34 glutamine residues. In individuals affected by Huntington's Disease, an autosomal dominant genetic disorder, it contains between 35-155 glutamine residues. Huntingtin has a predicted mass of ~350kDa, however, this varies and is largely dependent on the number of glutamine residues in the protein. Normal huntingtin is generally accepted to be 3144 amino acids in size.

Function

The function of Huntingtin is unclear. It is essential for development and absence of huntingtin is lethal in mice. The protein has no sequence homology with other proteins and is highly expressed in neurons and testes in humans and rodents. Normal huntingtin function: an alternative approach to Huntington's disease, Cattaneo E, Zuccato C, Tartari M, , , Nature Reviews Neuroscience, It has however been experimentally demonstrated that Huntingtin acts as a transcription factor in upregulating the expression of Brain Derived Neurotrophic Factor (BDNF). In the deficient protein, there is suppression of this transcription regulatory function of Huntingtin and hence underexpression of BDNF. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease, Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, et al, , , Science,
From immunohistochemistry, electron microscopy, subcellular fractionation studies of the molecule, it has been found that Huntingtin is primarily associated with vesicles and microtubules. Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with β-tubulin: relevance to Huntington's disease, Hoffner G, Kahlem P, Djian P, , , J Cell Sci, Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons, DiFiglia M, et al., , , Neuron, .These appear to indicate a functional role in cytoskeletal anchoring or transport of mitochondria.
Huntingtin has also been found to interact with a number of proteins. One such protein is the Huntingtin Interacting Protein I (HIP-I/Hip-1). HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system, Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, et al, , , Hum. Mol. Genet., Unfortunately the actions mediated via these interactions of huntingtin with the complementary interacting proteins is not fully understood.

Abnormal huntingtin

The key sequence which is found in Huntington's disease (HD) is a stretch of glutamine residues beginning at the 18th amino acid. In unaffected individuals, this stretch contains between 9 and 35 glutamine residues with no adverse effects. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes, Huntington's Disease Collaborative Research Group, , , Cell, However, individuals with HD have an expansion up to around 100 glutamines in this region of the gene. A greater number of residues is associated with earlier onset of the disease.

History

Huntingtin was identified in 1993.^[1]

References

1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group, , , , Cell, 1993

External links

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