Fungal Hal3 (and Its Close Relative Cab3) as Moonlighting Proteins

Hal3 (Sis2) is a yeast protein that was initially identified as a regulatory subunit of the Saccharomyces cerevisiae Ser/Thr protein phosphatase Ppz1. A few years later, it was shown to participate in the formation of an atypical heterotrimeric phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme, thus catalyzing a key reaction in the pathway leading to Coenzyme A biosynthesis. Therefore, Hal3 was defined as a moonlighting protein. The structure of Hal3 in some fungi is made of a conserved core, similar to bacterial or mammalian PPCDCs; meanwhile, in others, the gene encodes a larger protein with N- and C-terminal extensions. In this work, we describe how Hal3 (and its close relative Cab3) participates in these disparate functions and we review recent findings that could make it possible to predict which of these two proteins will show moonlighting properties in fungi.