PIKFYVE Antibody – Rabbit Polyclonal

Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

PIKFYVE: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo- inositol ring, to form phosphatidylinositol 3,5-bisphosphate. Required for endocytic-vacuolar pathway and nuclear migration. Plays a role in the biogenesis of endosome carrier vesicles (ECV)/ multivesicular bodies (MVB) transport intermediates from early endosomes. Defects in PIKFYVE are the cause of corneal fleck dystrophy (CFD). CFD is an autosomal dominant disorder of the cornea characterized by numerous small white flecks scattered in all levels of the stroma. Although CFD may occasionally cause mild photophobia, patients are typically asymptomatic and have normal vision. 4 isoforms of the human protein are produced by alternative splicing.

Protein type: Kinase, lipid; Carbohydrate Metabolism - inositol phosphate; Motility/polarity/chemotaxis; EC 2.7.1.150

Chromosomal Location of Human Ortholog: 2q34

Cellular Component: Golgi membrane; perinuclear region of cytoplasm; early endosome membrane; late endosome membrane; endosome membrane; cytoplasmic vesicle; intercellular junction; cytosol; lipid raft

Molecular Function: protein binding; 1-phosphatidylinositol-3-phosphate 5-kinase activity; 1-phosphatidylinositol-4-phosphate 5-kinase activity; phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; metal ion binding; ATP binding

Biological Process: myelin formation; receptor-mediated endocytosis; cellular protein metabolic process; phosphoinositide phosphorylation; phospholipid metabolic process; phosphatidylinositol biosynthetic process; retrograde transport, endosome to Golgi

Disease: Corneal Dystrophy, Fleck