VPS4A

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. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. 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.

Vacuolar Protein Sorting 4 Homolog A

Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. It is required for proper accomplishment of various processes including the regulation of endosome size, primary cilium organization, mitotic spindle organization, chromosome segregation, and nuclear envelope sealing and spindle disassembly during anaphase (PubMed:33186545).
Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission (PubMed:24814515).
VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).
Critical for normal erythroblast cytokinesis and correct erythropoiesis (PubMed:33186543).
(Microbial infection) In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses).

Biological Process abscission Source:UniProtKB1 Publication
Biological Process actomyosin contractile ring contraction Source:ARUK-UCL1 Publication
Biological Process autophagosome maturation Source:ComplexPortal1 Publication
Biological Process autophagy Source:ComplexPortal1 Publication
Biological Process cell division Source:UniProtKB1 Publication
Biological Process cytoskeleton-dependent cytokinesis Source:ARUK-UCL1 Publication
Biological Process endosomal transport Source:UniProtKB2 Publications
Biological Process endosomal vesicle fusion Source:UniProtKB1 Publication
Biological Process ESCRT complex disassembly Source:ParkinsonsUK-UCL1 Publication
Biological Process ESCRT III complex disassembly Source:ParkinsonsUK-UCL2 Publications
Biological Process intracellular cholesterol transport Source:UniProtKB1 Publication
Biological Process late endosomal microautophagy Source:ParkinsonsUK-UCL
Biological Process late endosome to lysosome transport via multivesicular body sorting pathway Source:ComplexPortal1 Publication
Biological Process macroautophagy Source:ParkinsonsUK-UCL1 Publication
Biological Process membrane fission Source:ComplexPortal1 Publication
Biological Process midbody abscission Source:UniProtKB1 Publication
Biological Process mitotic cytokinesis checkpoint signaling Source:UniProtKB1 Publication
Biological Process mitotic metaphase plate congression Source:UniProtKB1 Publication
Biological Process mitotic nuclear membrane reassembly Source:Reactome
Biological Process multivesicular body assembly Source:ParkinsonsUK-UCL
Biological Process multivesicular body sorting pathway Source:ComplexPortal1 Publication
Biological Process negative regulation of cell death Source:ComplexPortal1 Publication
Biological Process negative regulation of cytokinesis Source:UniProtKB1 Publication
Biological Process nuclear envelope organization Source:ARUK-UCL1 Publication
Biological Process nuclear membrane reassembly Source:ARUK-UCL1 Publication
Biological Process nucleus organization Source:UniProtKB1 Publication
Biological Process plasma membrane repair Source:ComplexPortal1 Publication
Biological Process positive regulation of exosomal secretion Source:UniProtKB1 Publication
Biological Process positive regulation of viral budding via host ESCRT complex Source:UniProtKB1 Publication
Biological Process protein targeting to lysosome Source:UniProtKB1 Publication
Biological Process regulation of protein localization Source:UniProtKB1 Publication
Biological Process regulation of protein localization to plasma membrane Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source:UniProtKB1 Publication
Biological Process ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway Source:UniProtKB1 Publication
Biological Process vacuole organization Source:GO_Central1 Publication
Biological Process vesicle budding from membrane Source:UniProtKB1 Publication
Biological Process vesicle uncoating Source:UniProtKB1 Publication
Biological Process vesicle-mediated transport Source:UniProtKB1 Publication
Biological Process viral budding from plasma membrane Source:UniProtKB2 Publications
Biological Process viral budding via host ESCRT complex Source:UniProtKB1 Publication
Biological Process viral release from host cell Source:UniProtKB1 Publication

Late endosome membrane
Midbody
Cytoplasm, cytoskeleton, spindle
Membrane-associated in the prevacuolar endosomal compartment. Localizes to the midbody of dividing cells, interaction with ZFYVE19/ANCHR mediates retention at midbody (PubMed:24814515).
Localized in two distinct rings on either side of the Flemming body.

CIMDAG syndrome (CIMDAG):
An autosomal dominant syndrome characterized by global developmental delay, severely impaired intellectual development, poor or absent speech, microcephaly, growth retardation, poor motor skills with inability to walk, hypotonia and spasticity, and cataracts. Cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination are apparent on brain imaging. Affected individuals show hematologic abnormalities mostly consistent with congenital dyserythropoietic anemia.