Polyphosphoinositide Phosphatase (FIG4) ELISA Kit for Human

The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

SAC3: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide substrates in the order PtdIns(4,5)P2 > PtdIns(3,5)P2 > PtdIns(3,4,5)P3. Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. Defects in FIG4 are the cause of Charcot-Marie-Tooth disease type 4J (CMT4J). CMT4J is a recessive demyelinating, severe form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. Defects in FIG4 are the cause of amyotrophic lateral sclerosis type 11 (ALS11). ALS is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10%.

Protein type: EC 3.1.3.-

Chromosomal Location of Human Ortholog: 6q21

Cellular Component: early endosome membrane; endoplasmic reticulum; endosome membrane; Golgi membrane; intracellular membrane-bound organelle; late endosome membrane; lipid droplet; recycling endosome

Molecular Function: phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; phosphatidylinositol-3-phosphatase activity; phosphatidylinositol-4-phosphate phosphatase activity; protein binding

Biological Process: dephosphorylation; locomotory behavior; myelin formation; negative regulation of myelination; neuron development; phosphatidylinositol biosynthetic process; pigmentation; positive regulation of neuron projection development; vacuole organization

Disease: Amyotrophic Lateral Sclerosis 11; Charcot-marie-tooth Disease, Type 4j; Polymicrogyria, Bilateral Temporooccipital; Yunis-varon Syndrome