NP_002102.4
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NCBI GenBank Nucleotide #
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UniProt Primary Accession #
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UniProt Secondary Accession #
UniProt Related Accession #
NCBI Official Full Name
huntingtin
NCBI Official Synonym Full Names
huntingtin
NCBI Official Synonym Symbols
NCBI Protein Information
huntingtin; huntington disease protein
UniProt Protein Name
Huntingtin
UniProt Synonym Protein Names
Huntington disease protein
UniProt Synonym Gene Names
UniProt Entry Name
HD_HUMAN
NCBI Summary for HTT
Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range in the number of trinucleotide repeats has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2008]
UniProt Comments for HTT
Function: May play a role in microtubule-mediated transport or vesicle function.
Subunit structure: Binds SH3GLB1
By similarity. Interacts through its N-terminus with PRPF40A. Interacts with PQBP1, SETD2 and SYVN. Interacts with PFN1. Interacts with TPR; the interaction is inhibited by forms of Huntingtin with expanded polyglutamine stretch. Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.20
Subcellular location: Cytoplasm. Nucleus. Note: The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington disease neurons. Shuttles between cytoplasm and nucleus in a Ran GTPase-independent manner. Ref.7 Ref.14 Ref.15
Tissue specificity: 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. Ref.15
Domain: 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. Ref.28
Post-translational modification: 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.Phosphorylation at Ser-1179 and Ser-1199 by CDK5 in response to DNA damage in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity.
Polymorphism: The poly-Gln region of HTT is highly polymorphic (10 to 35 repeats) in the normal population and is expanded to about 36-120 repeats in Huntington disease patients. The repeat length usually increases in successive generations, but contracts also on occasion. The adjacent poly-Pro region is also polymorphic and varies between 7-12 residues. Polyglutamine expansion leads to elevated susceptibility to apopain cleavage and likely result in accelerated neuronal apoptosis.
Involvement in disease: Huntington disease (HD) [MIM:143100]: A 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. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen.Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities: Belongs to the huntingtin family.Contains 5 HEAT repeats.
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Products associated with HTT blocking peptide
Pathways associated with HTT blocking peptide
Diseases associated with HTT blocking peptide
Organs/Tissues associated with HTT blocking peptide
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