VAC14


Description

The VAC14 (VAC14 component of PIKFYVE complex) is a protein-coding gene located on chromosome 16.

VAC14, also known as ArPIKfyve, is a protein encoded by the VAC14 gene in humans. It plays a critical role in regulating the levels of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes. VAC14 acts as a scaffold protein, forming a complex with PIKFYVE and Sac3. PIKFYVE is an enzyme responsible for synthesizing PtdIns(3,5)P2, while Sac3 is a phosphatase that removes phosphate groups. VAC14 activates PIKFYVE and protects Sac3 from degradation. In addition to this complex, VAC14 interacts with other proteins, including the PtdIns(3,5)P2-specific phosphatase Sac3, forming a stable complex with it. VAC14 also forms homooligomers through its carboxyl terminus. The exact number of monomers in the different complexes is unknown. Knockout studies in mice have shown that VAC14 is crucial for maintaining normal levels of PtdIns(3,5)P2, as well as another rare phosphoinositide, phosphatidylinositol 5-phosphate. These findings highlight the importance of VAC14 in regulating phosphoinositide metabolism and vesicle trafficking.

VAC14 is a scaffold protein that forms a complex with PIKFYVE and FIG4 to regulate the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). VAC14 pentamerizes into a star-shaped structure, binding one copy each of PIKFYVE and FIG4, and coordinating their activities. This complex is essential for maintaining normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P) and plays a role in the formation of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.

VAC14 is also known as ArPIKfyve, TAX1BP2, TRX.

Associated Diseases


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