There is no strict consensus sequence for palmitoylation, however, palmitoylated cysteines do share some common characteristics: (a) they are often adjacent to myristoylation and prenylation sites, (b) the surrounding amino acids tend to be basic or hydrophobic, and (c) they are frequently located in the cytoplasmic regions flanking transmembrane domains (or within transmembrane domains). An elegant combined proteomic and genetic analysis in yeast revealed that some DHHC proteins appear to exhibit a preference for a particular class of substrate, e.g., transmembrane proteins or myristoylated/ prenylated proteins (Roth et al., 2006) . Similarly, some palmitoylated yeast proteins displayed a marked dependence on a specific DHHC protein (of which seven are expressed in yeast). However, this study also revealed that DHHC proteins can have overlapping substrate specificities, which is consistent with previous studies in mammalian systems showing that specific substrates can be palmitoylated by more than one DHHC protein (Fukata et al., 2004; Fang et al., 2006; Fernández-Hernando et al., 2006; Greaves et al., 2008 Greaves et al., , 2010 Tsutsumi et al., 2009; Shmueli et al., 2010) .