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The huntingtin gene, also called HTT or HD (Huntington disease) gene, is the IT15 ("interesting transcript 15") gene which codes for a protein called the huntingtin protein.^[2] The gene and its product are under heavy investigation as part of Huntington's disease clinical research.

It is variable in its structure, as the many polymorphisms of the gene can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal) form, it contains 6-35 glutamine residues. However, in individuals affected by Huntington's disease (an autosomal dominant genetic disorder), it contains greater than 36 glutamine residues (highest reported repeat length is about 250).^[3] Its commonly used name is derived from this disease; previously, the IT15 label was commonly used.

The mass of huntingtin protein is dependent largely on the number of glutamine residues it has, the predicted mass is around 350 kDa. Normal huntingtin is generally accepted to be 3144 amino acids in size. The exact function of this protein is not known, but it plays an important role in nerve cells. Within cells, huntingtin may be involved in signaling, transporting materials, binding proteins and other structures, and protecting against programmed cell death (apoptosis). The huntingtin protein is required for normal development before birth.^[4] It is expressed in many tissues in the body, with the highest levels of expression seen in the brain.

Gene[edit]

The 5' end of the HD gene has a sequence of three DNA bases, cytosine-adenine-guanine (CAG), coding for the amino acid glutamine, that is repeated multiple times. This region is called a trinucleotide repeat. Normal persons have a CAG repeat count of between seven and 35 repeats.

The HD gene is located on the short (p) arm of chromosome 4 at position 16.3, from base pair 3,113,411 to base pair 3,282,655.

Protein[edit]

Function[edit]

The function of huntingtin is unclear. It is essential for development, and absence of huntingtin is lethal in mice.^[4] The protein has no sequence homology with other proteins and is highly expressed in neurons and testes in humans and rodents.^[5] Huntingtin upregulates the expression of Brain Derived Neurotrophic Factor (BDNF) at the transcription level, but the mechanism by which huntingtin regulates gene expression has not been determined.^[6] From immunohistochemistry, electron microscopy, and subcellular fractionation studies of the molecule, it has been found that huntingtin is primarily associated with vesicles and microtubules.^[7]^[7]^[8] These appear to indicate a functional role in cytoskeletal anchoring or transport of mitochondria. The Htt protein is involved in vesicle trafficking as it interacts with HIP1, a clathrin-binding protein, to mediate endocytosis, the absorption of materials into a cell.^[9]^[10]

Interactions[edit]

Huntingtin has been found to interact directly with at least 19 other proteins, of which six are used for transcription, four for transport, three for cell signalling, and six others of unknown function (HIP5, HIP11, HIP13, HIP15, HIP16, and CGI-125).^[11] Over 100 interacting proteins have been found, such as huntingtin-associated protein 1 (HAP1) and huntingtin interacting protein 1 (HIP1), these were typically found using two-hybrid screening and confirmed using immunoprecipitation.^[12]^[13]

Interacting Protein	PolyQ length dependence	Function
α-adaptin C/HYPJ	Yes	Endocytosis
Akt/PKB	No	Kinase
CBP	Yes	Transcriptional co-activator with acetyltransferase activity
CA150	No	Transcriptional activator
CIP4	Yes	cdc42-dependent signal transduction
CtBP	Yes	Transcription factor
FIP2	Not known	Cell morphogenesis
Grb2^[14]	Not known	Growth factor receptor binding protein
HAP1	Yes	Membrane trafficking
HAP40	Not known	Unknown
HIP1	Yes	Endocytosis, proapoptotic
HIP14/HYP-H	Yes	Trafficking, endocytosis
N-CoR	Yes	Nuclear receptor co-repressor
NF-κB	Not known	Transcription factor
p53^[15]	No	Transcription factor
PACSIN1^[16]	Yes	Endocytosis, actin cytoskeleton
PSS-95	Yes	Synaptic scaffolding protein
RasGAP	Not known	Ras GTPase activating protein
SH3GL3^[17]	Yes	Endocytosis
SIN3A	Yes	Transcriptional repressor
Sp1^[18]	Yes	Transcription factor

Huntingtin has also been shown to interact with:

HIP2,^[19]
MAP3K10,^[20]
OPTN,^[21]
PRPF40A,^[22]
RASA1,^[14]
SETD2,^[22]
TRIP10,^[23]
ZDHHC17.^[22]^[24]

Clinical significance[edit]

Main article: Huntington's disease

Huntington's disease (HD) is caused by a mutation in the huntingtin gene, where the CAG repeats more than 36 times and is unstable.^[25] These expanded repeats lead to production of a huntingtin protein that contains an abnormally long polyglutamine tract at the N-terminus. This makes it part of a class of neurodegenerative disorders known as trinucleotide repeat disorders or polyglutamine disorders. The key sequence which is found in Huntington's disease is a trinucleotide repeat expansion of glutamine residues beginning at the 18th amino acid. In unaffected individuals, this contains between 9 and 35 glutamine residues with no adverse effects.^[26] However, 36 or more residues produce an erroneous form of Htt, mHtt (standing for mutant Htt). Reduced penetrance is found in counts 36-39.^[27]

Enzymes in the cell often cut this elongated protein into fragments. The protein fragments form abnormal clumps, known as neuronal intranuclear inclusions (NIIs), inside nerve cells, and may attract other, normal proteins into the clumps. The presence of these clumps was once thought to play a causal role in Huntington disease.^[28] Further research undermined this conclusion by showing the presence of NIIs actually extended the life of neurons and acted to reduce intracellular mutant huntingtin in neighboring neurons.^[29] Thus, the likelihood of neuronal death can be predicted by accounting for two factors: (1) the length of CAG repeats in the Huntingtin gene and (2) the neuron's exposure to diffuse intracellular mutant huntingtin protein. NIIs (protein clumping) can thereby be construed as a coping mechanism—as opposed to a pathogenic mechanism—to stem neuronal death by decreasing the amount of diffuse huntingtin.^[30] This process is particularly likely to occur in the striatum (a part of the brain that coordinates movement) primarily, and the frontal cortex (a part of the brain that controls thinking and emotions).

Classification of the trinucleotide repeat, and resulting disease status, depends on the number of CAG repeats^[25]
Repeat count	Classification	Disease status
<28	Normal	Unaffected
28–35	Intermediate	Unaffected
36–40	Reduced penetrance	+/- Affected
>40	Full penetrance	Affected

People with 36 to 40 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with more than 40 repeats will develop the disorder during a normal lifetime. When there are more than 60 CAG repeats, the person develops a severe form of HD known as juvenile HD. Therefore, the number of CAG (the sequence coding for the amino acid glutamine) repeats influences the age of onset of the disease. No case of HD has been diagnosed with a count less than 36.^[27]

As the altered gene is passed from one generation to the next, the size of the CAG repeat expansion can change; it often increases in size, especially when it is inherited from the father. People with 28 to 35 CAG repeats have not been reported to develop the disorder, but their children are at risk of having the disease if the repeat expansion increases.

References[edit]

^ PDB 3io4; Kim MW, Chelliah Y, Kim SW, Otwinowski Z, Bezprozvanny I (September 2009). "Secondary structure of Huntingtin amino-terminal region". Structure 17 (9): 1205–12. doi:10.1016/j.str.2009.08.002. PMID 19748341.
^ The Huntington's Disease Collaborative Research Group (March 1993). "A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes". Cell 72 (6): 971–83. doi:10.1016/0092-8674(93)90585-E. PMID 8458085.
^ Nance MA, Mathias-Hagen V, Breningstall G, Wick MJ, McGlennen RC (January 1999). "Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington's disease". Neurology 52 (2): 392–4. PMID 9932964.
^ ^a ^b Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR (June 1995). "Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes". Cell 81 (5): 811–23. doi:10.1016/0092-8674(95)90542-1. PMID 7774020.
^ Cattaneo E, Zuccato C, Tartari M (December 2005). "Normal huntingtin function: an alternative approach to Huntington's disease". Nature Reviews. Neuroscience 6 (12): 919–30. doi:10.1038/nrn1806. PMID 16288298.
^ Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E (July 2001). "Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease". Science 293 (5529): 493–8. doi:10.1126/science.1059581. PMID 11408619.
^ ^a ^b Hoffner G, Kahlem P, Djian P (March 2002). "Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease". Journal of Cell Science 115 (Pt 5): 941–8. PMID 11870213.
^ DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, Martin E, Vonsattel JP, Carraway R, Reeves SA (May 1995). "Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons". Neuron 14 (5): 1075–81. doi:10.1016/0896-6273(95)90346-1. PMID 7748555.
^ Velier J, Kim M, Schwarz C, Kim TW, Sapp E, Chase K, Aronin N, DiFiglia M (July 1998). "Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways". Experimental Neurology 152 (1): 34–40. doi:10.1006/exnr.1998.6832. PMID 9682010.
^ Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE (August 2001). "The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis". Human Molecular Genetics 10 (17): 1807–17. doi:10.1093/hmg/10.17.1807. PMID 11532990.
^ Harjes P, Wanker EE (August 2003). "The hunt for huntingtin function: interaction partners tell many different stories". Trends in Biochemical Sciences 28 (8): 425–33. doi:10.1016/S0968-0004(03)00168-3. PMID 12932731.
^ Goehler H, Lalowski M, Stelzl U, et al. (September 2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease". Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276. Retrieved 2009-04-27.
^ Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, et al. (March 1997). "HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system". Hum. Mol. Genet. 6 (3): 487–95. doi:10.1093/hmg/6.3.487. PMID 9147654.
^ ^a ^b Liu, Y F; Deth R C, Devys D (March 1997). "SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes". J. Biol. Chem. (UNITED STATES) 272 (13): 8121–4. doi:10.1074/jbc.272.13.8121. ISSN 0021-9258. PMID 9079622.
^ Steffan, J S; Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu Y Z, Gohler H, Wanker E E, Bates G P, Housman D E, Thompson L M (June 2000). "The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (12): 6763–8. doi:10.1073/pnas.100110097. ISSN 0027-8424. PMC 18731. PMID 10823891.
^ Modregger, January; DiProspero Nicholas A, Charles Vinod, Tagle Danilo A, Plomann Markus (October 2002). "PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains". Hum. Mol. Genet. (England) 11 (21): 2547–58. doi:10.1093/hmg/11.21.2547. ISSN 0964-6906. PMID 12354780.
^ Sittler, A; Wälter S, Wedemeyer N, Hasenbank R, Scherzinger E, Eickhoff H, Bates G P, Lehrach H, Wanker E E (October 1998). "SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates". Mol. Cell (UNITED STATES) 2 (4): 427–36. doi:10.1016/S1097-2765(00)80142-2. ISSN 1097-2765. PMID 9809064.
^ Li, Shi-Hua; Cheng Anna L, Zhou Hui, Lam Suzanne, Rao Manjula, Li He, Li Xiao-Jiang (March 2002). "Interaction of Huntington Disease Protein with Transcriptional Activator Sp1". Mol. Cell. Biol. (United States) 22 (5): 1277–87. doi:10.1128/MCB.22.5.1277-1287.2002. ISSN 0270-7306. PMC 134707. PMID 11839795.
^ Kalchman MA, Graham RK, Xia G, Koide HB, Hodgson JG, Graham KC, Goldberg YP, Gietz RD, Pickart CM, Hayden MR (August 1996). "Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme". J. Biol. Chem. 271 (32): 19385–94. doi:10.1074/jbc.271.32.19385. PMID 8702625.
^ Liu YF, Dorow D, Marshall J (June 2000). "Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin". J. Biol. Chem. 275 (25): 19035–40. doi:10.1074/jbc.C000180200. PMID 10801775.
^ Hattula K, Peränen J (2000). "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis". Curr. Biol. 10 (24): 1603–6. doi:10.1016/S0960-9822(00)00864-2. PMID 11137014.
^ ^a ^b ^c Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (September 1998). "Huntingtin interacts with a family of WW domain proteins". Hum. Mol. Genet. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.
^ Holbert S, Dedeoglu A, Humbert S, Saudou F, Ferrante RJ, Néri C (March 2003). "Cdc42-interacting protein 4 binds to huntingtin: Neuropathologic and biological evidence for a role in Huntington's disease". Proc. Natl. Acad. Sci. U.S.A. 100 (5): 2712–7. doi:10.1073/pnas.0437967100. PMC 151406. PMID 12604778.
^ Singaraja RR, Hadano S, Metzler M, Givan S, Wellington CL, Warby S, Yanai A, Gutekunst CA, Leavitt BR, Yi H, Fichter K, Gan L, McCutcheon K, Chopra V, Michel J, Hersch SM, Ikeda JE, Hayden MR (November 2002). "HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis". Hum. Mol. Genet. 11 (23): 2815–28. doi:10.1093/hmg/11.23.2815. PMID 12393793.
^ ^a ^b Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28. doi:10.1016/S0140-6736(07)60111-1. PMID 17240289.
^ 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 (6): 971–983. doi:10.1016/0092-8674(93)90585-E. PMID 8458085.
^ ^a ^b Chong SS, Almqvist E, Telenius H, LaTray L, Nichol K, Bourdelat-Parks B, Goldberg YP, Haddad BR, Richards F, Sillence D, Greenberg CR, Ives E, Van den Engh G, Hughes MR, Hayden MR (February 1997). "Contribution of DNA sequence and CAG size to mutation frequencies of intermediate alleles for Huntington disease: evidence from single sperm analyses". Human Molecular Genetics 6 (2): 301–9. PMID 9063751.
^ Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (August 1997). "Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation". Cell 90 (3): 537–48. doi:10.1016/S0092-8674(00)80513-9. PMID 9267033.
^ Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004). "Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death". Nature 431 (7010): 805–810. doi:10.1038/nature02998. PMID 15483602.
^ Orr HT (October 2004). "Neurodegenerative disease: neuron protection agency". Nature 431 (7010): 747–8. doi:10.1038/431747a. PMID 15483586.

External links[edit]

Huntingtin protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
The Huntingtin Protein and Protein Aggregation at HOPES : Huntington's Outreach Project for Education at Stanford
The HDA Huntington's Disease Association UK
Online 'Mendelian Inheritance in Man' (OMIM) 143100
EntrezGene 3064
GeneCard
iHOP

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. ハンチントン病：遺伝学と病因 huntington disease genetics and pathogenesis
2. ハンチントン病：臨床的特徴および診断 huntington disease clinical features and diagnosis
3. ハンチントン病：管理 huntington disease management
4. 小児における運動減少性運動障害 bradykinetic movement disorders in children
5. 舞踏病の概要 overview of chorea

English Journal

Huntingtin disrupts lipid bilayers in a polyQ-length dependent manner.

Burke KA, Hensal KM, Umbaugh CS, Chaibva M, Legleiter J.SourceThe C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26505, USA.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Aug;1828(8):1953-61. doi: 10.1016/j.bbamem.2013.04.025. Epub 2013 May 2.
Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, su
PMID 23643759

Seeking huntington disease biomarkers by multimodal, cross-sectional basal ganglia imaging.

Sánchez-Castañeda C, Cherubini A, Elifani F, Péran P, Orobello S, Capelli G, Sabatini U, Squitieri F.SourceDepartment of Radiology, IRCCS Santa Lucia, Rome, Italy; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPS, Barcelona, Spain.
Human brain mapping.Hum Brain Mapp.2013 Jul;34(7):1625-35. doi: 10.1002/hbm.22019. Epub 2012 Feb 22.
Neurodegeneration of the striatum in Huntington disease (HD) is characterized by loss of medium-spiny neurons, huntingtin nuclear inclusions, reactive gliosis, and iron accumulation. Neuroimaging allows in vivo detection of the macro- and micro-structural changes that occur from presymptomatic stage
PMID 22359398

Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data.

Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, Borowsky B, Landwehrmeyer B, Frost C, Johnson H, Craufurd D, Reilmann R, Stout JC, Langbehn DR; TRACK-HD Investigators.SourceUCL Institute of Neurology, University College London, London, UK. Electronic address: sarah.tabrizi@prion.ucl.ac.uk.
Lancet neurology.Lancet Neurol.2013 Jul;12(7):637-49. doi: 10.1016/S1474-4422(13)70088-7. Epub 2013 May 9.
BACKGROUND: TRACK-HD is a multinational prospective observational study of Huntington's disease (HD) that examines clinical and biological findings of disease progression in individuals with premanifest HD (preHD) and early-stage HD. We aimed to describe phenotypic changes in these participants over
PMID 23664844

Japanese Journal

Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation

Tashiro Erika,Zako Tamotsu,Muto Hideki,Itoo Yoshinori,Soergjerd Karin,Terada Naofumi,Abe Akira,Miyazawa Makoto,Kitamura Akira,Kitaura Hirotake,Kubota Hiroshi,Maeda Mizuo,Momoi Takashi,Iguchi-Ariga Sanae M. M.,Kinjo Masataka,Ariga Hiroyoshi
Journal of Biological Chemistry 288(27), 19958-19972, 2013-07-05
… Huntington disease is caused by cell death after the expansion of polyglutamine (polyQ) tracts longer than similar to 40 repeats encoded by exon 1 of the huntingtin (HTT) gene. …
NAID 120005323603

胃壁細胞における胃酸分泌の分子基盤

浅野真司
膜 36(6), 278-285, 2011-11-01
… Thirdly, I wish to introduce actin-binding proteins, ezrin and Huntingtin interacting protein 1 related (Hip1r), which are necessary for gastric acid secretion. …
NAID 10030449851

3L1434 Aberrant cAMP responses in huntingtin-null cells in Dictyostelium(Cell biology 5,The 49th Annual Meeting of the Biophysical Society of Japan)

Fukujin Fumihito,Ando Chie,Kuwayama Hidekazu,Sawai Satoshi
生物物理 51(SUPPLEMENT_1), S149, 2011-08-15
NAID 110008903601

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リンク元	「ハンチントン病遺伝子」

「ハンチントン病遺伝子」

Huntingtin
	; Crystallographic structure of the N-terminal region of the human Huntingtin protein with an artificially attached Maltose-Binding protein used for crystallographic purposes.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2LD0, 2LD2, 3IO4, 3IO6, 3IOR, 3IOT, 3IOU, 3IOV, 3IOW, 3LRH, 4FE8, 4FEB, 4FEC, 4FED
Identifiers
Symbols	HTT; HD; IT15
External IDs	OMIM: 613004 MGI: 96067 HomoloGene: 1593 ChEMBL: 5514 GeneCards: HTT Gene
Gene Ontology
Molecular function	• p53 binding; • protein binding; • transcription factor binding; • dynactin binding; • dynein intermediate chain binding; • beta-tubulin binding; • diazepam binding;
Cellular component	• nucleus; • nucleolus; • cytoplasm; • late endosome; • autophagic vacuole; • endoplasmic reticulum; • Golgi apparatus; • cytosol; • inclusion body; • axon; • dendrite; • cytoplasmic vesicle membrane; • protein complex;
Biological process	• urea cycle; • citrulline metabolic process; • establishment of mitotic spindle orientation; • protein import into nucleus; • ER to Golgi vesicle-mediated transport; • retrograde vesicle-mediated transport, Golgi to ER; • endoplasmic reticulum organization; • Golgi organization; • dopamine receptor signaling pathway; • spermatogenesis; • cell aging; • locomotory behavior; • axon cargo transport; • determination of adult lifespan; • visual learning; • anterior/posterior pattern specification; • endosomal transport; • lactate biosynthetic process from pyruvate; • quinolinate biosynthetic process; • striatum development; • olfactory lobe development; • neural plate formation; • insulin secretion; • regulation of protein phosphatase type 2A activity; • social behavior; • hormone metabolic process; • negative regulation of neuron apoptotic process; • regulation of protein export from nucleus; • regulation of mitochondrial membrane permeability; • vesicle transport along microtubule; • regulation of synaptic plasticity; • paraxial mesoderm formation; • organ development; • neuron development; • neuron apoptotic process; • response to calcium ion; • regulation of mitochondrial membrane potential; • L-glutamate import; • iron ion homeostasis; • negative regulation of extrinsic apoptotic signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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　　[★]

英: Huntington disease gene
同: ハンチンチン huntingtin、ハンチンチン遺伝子 huntingtin gene、IT15遺伝子 IT15 gene
関: ハンチントン病

[pmid19748341-1] PDB 3io4; Kim MW, Chelliah Y, Kim SW, Otwinowski Z, Bezprozvanny I (September 2009). "Secondary structure of Huntingtin amino-terminal region". Structure 17 (9): 1205–12. doi:10.1016/j.str.2009.08.002. PMID 19748341.

[pmid8458085-2] The Huntington's Disease Collaborative Research Group (March 1993). "A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes". Cell 72 (6): 971–83. doi:10.1016/0092-8674(93)90585-E. PMID 8458085.

[pmid9932964-3] Nance MA, Mathias-Hagen V, Breningstall G, Wick MJ, McGlennen RC (January 1999). "Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington's disease". Neurology 52 (2): 392–4. PMID 9932964.

[pmid7774020-4] Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR (June 1995). "Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes". Cell 81 (5): 811–23. doi:10.1016/0092-8674(95)90542-1. PMID 7774020.

[pmid16288298-5] Cattaneo E, Zuccato C, Tartari M (December 2005). "Normal huntingtin function: an alternative approach to Huntington's disease". Nature Reviews. Neuroscience 6 (12): 919–30. doi:10.1038/nrn1806. PMID 16288298.

[pmid11408619-6] Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E (July 2001). "Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease". Science 293 (5529): 493–8. doi:10.1126/science.1059581. PMID 11408619.

[pmid11870213-7] Hoffner G, Kahlem P, Djian P (March 2002). "Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease". Journal of Cell Science 115 (Pt 5): 941–8. PMID 11870213.

[pmid7748555-8] DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, Martin E, Vonsattel JP, Carraway R, Reeves SA (May 1995). "Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons". Neuron 14 (5): 1075–81. doi:10.1016/0896-6273(95)90346-1. PMID 7748555.

[pmid9682010-9] Velier J, Kim M, Schwarz C, Kim TW, Sapp E, Chase K, Aronin N, DiFiglia M (July 1998). "Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways". Experimental Neurology 152 (1): 34–40. doi:10.1006/exnr.1998.6832. PMID 9682010.

[pmid11532990-10] Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE (August 2001). "The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis". Human Molecular Genetics 10 (17): 1807–17. doi:10.1093/hmg/10.17.1807. PMID 11532990.

[pmid12932731-11] Harjes P, Wanker EE (August 2003). "The hunt for huntingtin function: interaction partners tell many different stories". Trends in Biochemical Sciences 28 (8): 425–33. doi:10.1016/S0968-0004(03)00168-3. PMID 12932731.

[pmid15383276-12] Goehler H, Lalowski M, Stelzl U, et al. (September 2004). "A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease". Mol. Cell 15 (6): 853–65. doi:10.1016/j.molcel.2004.09.016. PMID 15383276. Retrieved 2009-04-27.

[Wanker-13] Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, et al. (March 1997). "HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system". Hum. Mol. Genet. 6 (3): 487–95. doi:10.1093/hmg/6.3.487. PMID 9147654.

[pmid9079622-14] Liu, Y F; Deth R C, Devys D (March 1997). "SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes". J. Biol. Chem. (UNITED STATES) 272 (13): 8121–4. doi:10.1074/jbc.272.13.8121. ISSN 0021-9258. PMID 9079622.

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huntingtin