A huntingtin-associated protein enriched in brain with implications for pathology

Nature. 1995 Nov 23;378(6555):398-402. doi: 10.1038/378398a0.


Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanding polyglutamine repeat in the IT15 or huntingtin gene. Although this gene is widely expressed and is required for normal development, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins. Here we report the identification of a protein (huntingtin-associated protein (HAP)-1) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism*
  • Brain / pathology
  • Cell Line
  • DNA Primers
  • Gene Library
  • Humans
  • Huntingtin Protein
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Transfection


  • DNA Primers
  • HAP1 protein, human
  • HTT protein, human
  • Hap1 protein, rat
  • Htt protein, rat
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins

Associated data

  • GENBANK/U38370
  • GENBANK/U38371
  • GENBANK/U38372
  • GENBANK/U38373