Analysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system

Mol Biol Cell. 2012 Dec;23(23):4543-51. doi: 10.1091/mbc.E12-05-0336. Epub 2012 Oct 3.

Abstract

Palmitoylation plays important roles in the regulation of protein localization, stability, and activity. The protein acyltransferases (PATs) have a common DHHC Cys-rich domain. Twenty-three DHHC proteins have been identified in humans. However, it is unclear whether all of these DHHC proteins function as PATs. In addition, their substrate specificities remain largely unknown. Here we develop a useful method to examine substrate specificities of PATs using a yeast expression system with six distinct model substrates. We identify 17 human DHHC proteins as PATs. Moreover, we classify 11 human and 5 yeast DHHC proteins into three classes (I, II, and III), based on the cellular localization of their respective substrates (class I, soluble proteins; class II, integral membrane proteins; class III, lipidated proteins). Our results may provide an important clue for understanding the function of individual DHHC proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / classification*
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Cysteine* / chemistry
  • Cysteine* / genetics
  • Gene Expression Regulation, Fungal
  • Humans
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / metabolism
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity

Substances

  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • protein acyltransferase
  • Cysteine