Identification and functional analysis of truncated human glutamic acid decarboxylase 65

J Biomed Sci. 2003;10(6 Pt 1):617-24. doi: 10.1159/000073527.


Human brain glutamate decarboxylase 65 (hGAD65) was found to exist as full-length and truncated forms when the glutathione S-transferase-tagged hGAD65 fusion protein was subjected to factor Xa cleavage. The truncated form is produced by cleavage at arginine 69 based on N-terminal amino acid sequence analysis, and has a molecular weight of 58 kD. It is resistant to further factor Xa cleavage or mild trypsin treatment and is more active and more stable than the full-length form. Both the full-length and truncated forms of GAD are also observed in brain preparations in the presence of protease inhibitors. Furthermore, full-length GAD could be converted to the truncated form by endogenous proteases, suggesting that the conversion of full-length to truncated GAD mediated by endogenous protease may represent an important mechanism in the regulation of GABA biosynthesis in the brain.

Publication types

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

MeSH terms

  • Brain / enzymology*
  • Brain Chemistry
  • Factor Xa / metabolism
  • Glutamate Decarboxylase / chemistry
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism*
  • Humans
  • Molecular Weight
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Factor Xa
  • Glutamate Decarboxylase