VPS4A
Description
The VPS4A (vacuolar protein sorting 4 homolog A) is a protein-coding gene located on chromosome 16.
Vacuolar protein sorting-associated protein 4A is a protein that in humans is encoded by the VPS4A gene. The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. They share a high degree of amino acid sequence similarity with each other, and also with yeast Vps4 and mouse proteins. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18.
VPS4A plays a crucial role in the late stages of the endosomal multivesicular body (MVB) pathway. It identifies and dismantles ESCRT-III complexes associated with membranes, potentially alongside membrane fission. This action releases ESCRT-III components back into the cytoplasm for further rounds of MVB sorting. MVBs are characterized by intraluminal vesicles (ILVs) formed through invagination and separation from the endosomal membrane. These ILVs primarily travel to lysosomes, facilitating the breakdown of membrane proteins like stimulated growth factor receptors, lysosomal enzymes, and lipids. VPS4A's involvement extends beyond MVB function, influencing processes like endosome size regulation, primary cilium organization, mitotic spindle arrangement, chromosome segregation, and nuclear envelope sealing and spindle disassembly during anaphase. During cytokinesis, VPS4A is retained at the midbody by ZFYVE19/ANCHR and CHMP4C, holding it until the abscission checkpoint signal ends in late cytokinesis. Once CHMP4C dephosphorylates, VPS4A is released, enabling abscission. VPS4A/B collaborate in the exosomal release of SDCBP, CD63, and syndecan. VPS4A is essential for normal erythroblast cytokinesis and proper erythropoiesis.
VPS4A is also known as CIMDAG, SKD1, SKD1A, SKD2, VPS4, VPS4-1.
