From Wikipedia, the free encyclopedia

huntingtin
Identifiers
Symbol	HD
HUGO	4851
Entrez	3064
OMIM	143100
RefSeq	NM_002111
UniProt	P42858
Other data
Locus	Chr. 4 p16.3

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

Contents 1 Introduction 2 Function 3 Abnormal huntingtin 4 References 5 External links

Huntingtin (Htt) is the protein coded by the HD gene. It is very 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.

The function of Huntingtin is unclear. It is essential for development and absence of huntingtin is lethal in mice.^[1] The protein has no sequence homology with other proteins and is highly expressed in neurons and testes in humans and rodents.^[2] 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.^[3]

From immunohistochemistry, electron microscopy, subcellular fractionation studies of the molecule, it has been found that Huntingtin is primarily associated with vesicles and microtubules.^[4][5].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).^[6] Unfortunately the actions mediated via these interactions of huntingtin with the complementary interacting proteins is not fully understood.

The key sequence which is found in Huntington's disease (HD) is a stretch of glutamineresidues beginning at the 18th amino acid. In unaffected individuals, this stretch can contain up to 34 glutamine residues with no adverse effects.^[7] However, individuals with HD have an expansion of the number of glutamines in this region of the gene.

1. ^ Nasir J, Floresco S, et al (1995). "Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes". Cell 81: 811–823. DOI:10.1016/0092-8674(95)90542-1. 
2. ^ Cattaneo E, Zuccato C, Tartari M (2005 Dec). "Normal huntingtin function: an alternative approach to Huntington's disease". Nature Reviews Neuroscience 6: 919-930. DOI:10.1038/nrn1806. 
3. ^ Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, et al (2001 Jul 20). "Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease". Science 293 (5529): 445-6. 
4. ^ Hoffner G, Kahlem P, Djian P (2002). "Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with β-tubulin: relevance to Huntington's disease". J Cell Sci 115: 941–948. 
5. ^ DiFiglia M, et al. (1995). "Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons". Neuron 14: 1075–1081. 
6. ^ Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, et al (1997 Mar). "HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system". Hum. Mol. Genet. 6 (3): 487-95. 
7. ^ Huntington's Disease Collaborative Research Group (1993). "A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes". Cell 72: 971–983. 

• Discovery