7k1w

Structural highlights

Disease

FIG4_HUMAN Amyotrophic lateral sclerosis;Bilateral parasagittal parieto-occipital polymicrogyria;Charcot-Marie-Tooth disease type 4J;Yunis-Varon syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

FIG4_HUMAN Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:17556371, PubMed:33098764). Catalyzes the dephosphorylation of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) to form phosphatidylinositol 3-phosphate (PubMed:33098764). Has serine-protein phosphatase activity acting on PIKfyve to stimulate its lipid kinase activity, its catalytically activity being required for maximal PI(3,5)P2 production (PubMed:33098764). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide and although displaying preferences for PtdIns(3,5)P2, it is capable of hydrolyzing PtdIns(3,4,5)P3 and PtdIns(4,5)P2, at least in vitro (PubMed:17556371).^{[1] [2]}

References

1. ↑ Sbrissa D, Ikonomov OC, Fu Z, Ijuin T, Gruenberg J, Takenawa T, Shisheva A. Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex. J Biol Chem. 2007 Aug 17;282(33):23878-91. PMID:17556371 doi:10.1074/jbc.M611678200
2. ↑ Lees JA, Li P, Kumar N, Weisman LS, Reinisch KM. Insights into Lysosomal PI(3,5)P2 Homeostasis from a Structural-Biochemical Analysis of the PIKfyve Lipid Kinase Complex. Mol Cell. 2020 Oct 15. pii: S1097-2765(20)30686-9. doi:, 10.1016/j.molcel.2020.10.003. PMID:33098764 doi:http://dx.doi.org/10.1016/j.molcel.2020.10.003