Phosphatase Subfamily FIG4
Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac: Subfamily FIG4 (SAC3)
Evolution
The FIG4 (SAC3) subfamily is conserved in eukaryotes. It is present in almost all the 203 eukaryotic genomes in gOrtholog database (internal).
Domain
The FIG4 (SAC3) subfamily has a single structural domain, SAC phosphatase domain.
Function
FIG4 is a phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) phosphatase. It functions in the complex with PIKfyve (the sole kinase for PtdIns(3,5)P2 synthesis) and the PIKfyve activator ArPIKfyve. The triple PIKfyve-ArPIKfyve-Sac3 (PAS) complex ensures the PtdIns(3,5)P2 homeostatic control by rapid turnover counterbalancing locally elevated PtdIns(3,5)P2. PtdIns(3,5)P2, a low abundance PI comprising as little as 0.8% of total PIs in mammalian cells, mediates essential aspects of endocytic membrane homeostasis and coordinates fission and fusion events in the multivesicular endosomal system of mammalian cells [1]. A model of domain interactions within the PAS core and their role in regulating the enzymatic activities was summarized in Figure 6 of [1].
