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Beschreibung

Vacuolar protein sorting-associated protein 4A (EC 3.6.4.6, UniProt Q9UN37, also known as hVPS4, Protein SKD2, SKD1-homolog, Vacuolar protein sorting factor 4A, Vacuolar sorting protein 4, VPS4A) is encoded by the VPS4A gene (also known as SKD1A, VPS4, VPS4-1) (Gene ID 27183) in human. Vps4 is a member of the ATPases associated with various cellular activities. The ESCRT (endosomal sorting complexes required for transport) machinery consists of five complexes (SCRT-0, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4) that mediate multiple cellular membrane remodeling events, ranging from multivesicular bodies and exosomes formation to the final membrane abscission stage of cytokinesis, all of which converge in the scission of the narrow membrane neck that connects bud to parent membrane or daughter cell to daughter cell. Scission depends on the polymerization of soluble ESCRT-III monomers or dimers into tightly membrane-bound filaments. Vps4 is essential for ESCRT function in cells and it mediates the disassembly of ESCRT-III filaments to ensure a constant replenishing of the pool of soluble ESCRT-III monomers. The ESCRTs are also exploited by HIV-1 and many other enveloped viruses for their escape from the host cells. Vps4A is reported to facilitate the secretion of oncogenic miRNAs in exosomes and downregulation of Vps4A in hepatocellular carcinoma (HCC) is associated with tumor progression and metastasis.