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evolution
enzyme SKD1 belongs to the AAA ATPase family
evolution
enzyme vacuolar protein sorting 4, Vps4, belongs to the AAA ATPases. Vps4 forms a hexameric complex that disassembles ESCRT-III, allowing recycling of its components, and also plays an active role in scission of the vesicle neck. Vps4 is required for epidermal growth factor receptor signaling even in the absence of Shibire, the Dynamin that internalizes epidermal growth factor receptor from the plasma membrane. In ovarian follicle cells, in contrast, Vps4 does not affect epidermal growth factor receptor signaling, although it is still essential for receptor degradation, Vps4 is not required for EGFR or Notch signaling in follicle cells. Enzyme Vps4 can promote epidermal growth factor receptor activity through an endocytosis-independent mechanism, a non-endocytic and cell type-dependent mechanism. Protein Vps4 is the only energy-utilizing ESCRT component
evolution
the enzyme Vps4 belongs to the type I AAA ATPases
evolution
human and Dictyostelium p97 share 81% identity and 89% similarity on the amino acid sequence level and have an almost identical order and composition of secondary structure elements
evolution
human and Dictyostelium p97 share 81% identity and 89% similarity on the amino acid sequence level and have an almost identical order and composition of secondary structure elements
malfunction
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inhibition of p97, but not NSF ATPase can be associated with ER/Golgi disruption and apoptosis in alphaSNAP-depleted epithelial cells. AlphaSNAP knockdown does not affect p97 expression, it perturbes a balance between key p97-binding partners. Specifically, expression of syntaxins 5 and 18 are significantly decreased
malfunction
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deletion of Vps4p in yeast leads to the formation of crescent-like membrane structures instead of the characteristic spherule and vesicle-like structures
malfunction
photoreceptors are largely absent from Vps4 mutant clones in the eye disc, the resulting mutant R8 photoreceptors fail to recruit surrounding cells to differentiate as R1-R7 photoreceptors. Loss of Vps4 disrupts the epidermal growth factor receptor, EGFR, pathway. In imaginal disc cells deficient for enzyme Vps4, EGFR and other receptors accumulate in endosomes, and EGFR target genes are not expressed
malfunction
heterozygous missense mutations of p97 cause at least five human neurodegenerative disorders, i.e. R93C, R155H, and R155C mutations. All human p97 mutations lead to an increase in ATPase activity. p97 point mutations lead to differences in enzymatic activities and molecular interactions, which in the long-term result in a late-onset and progressive multisystem disease
malfunction
p97 point mutations lead to differences in enzymatic activities and molecularinteractions, which in the long-term result in a late-onset and progressive multisystem disease
malfunction
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subunit Atp6v0d2-deficient macrophages have augmented mitochondrial damage, enhanced inflammasome activation and reduced clearance of Salmonella typhimurium
malfunction
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deletion of Vps4p in yeast leads to the formation of crescent-like membrane structures instead of the characteristic spherule and vesicle-like structures
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metabolism
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vesicle trafficking in eukaryotic cells is facilitated by SNARE-mediated membrane fusion. The ATPase N-ethylmaleimide-sensitive factor, NSF, and the adaptor protein soluble NSF attachment protein, alpha-SNAP, disassemble all SNARE complexes formed throughout different pathways
metabolism
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the enzyme functions in membrane remodelling and is the only ATP consuming factor of the endosomal sorting complex required for transport (ESCRT) machinery. ATP hydrolysis is required to disassemble ESCRT-III polymers, which releases individual ESCRT-III subunits back into the cytoplasm
physiological function
the enzyme provides energy for the ESCRT (endosomal sorting complexes required for transport) pathway
physiological function
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Vps4 functions together with the protein complex ESCRT-III in membrane fission
physiological function
enzyme SKD1 is involved in multivesicular bodies biogenesis, the LIP5-regulated multivesicular bodies biogenesis, MVB, pathway also plays a critical role in plant responses to abiotic stresses. The critical role of LIP5 in plant tolerance to abiotic stresses is dependent on its ability to interact with the enzyme SKD1
physiological function
enzyme vacuolar protein sorting 4, Vps4, interacts with the endosomal sorting complexes required for transport, ESCRT-III, complex to drive the final step of intra-lumenal vesicles formation
physiological function
the endosomal sorting complexes required for transport (ESCRT) pathway drives reverse topology membrane fission events within multiple cellular pathways, including cytokinesis, multivesicular body biogenesis, repair of the plasma membrane, nuclear membrane vesicle formation, and HIV budding. The AAA ATPase Vps4 is recruited to membrane necks shortly before fission, where it catalyzes disassembly of the ESCRT-III lattice. Vps4 substrates are initially recruited by an MIM-MIT interaction that activates the Vps4 central pore to engage substrates and generate force, thereby triggering ESCRT-III disassembly. Vps2p helix 5 peptides bind the Vps4p ATPase cassette. Two-step model for disassembly of the ESCRT-III complex by Vps4, overview
physiological function
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vesicle trafficking in eukaryotic cells is facilitated by SNARE-mediated membrane fusion. The ATPase N-ethylmaleimide-sensitive factor, NSF, and the adaptor protein soluble NSF attachment protein, alpha-SNAP, disassemble all SNARE complexes formed throughout different pathways. SNARE-stimulated ATP hydrolysis. Modeling of NSF-mediated disassembly in which the reaction is initiated by a 1:1 interaction between alpha-SNAP and the ternary SNARE complex, followed by NSF binding. Subsequent additional alpha-SNAP binding events may occur as part of a processive disassembly mechanism
physiological function
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Vps4p is required for the formation of spherule-like structures induced by tombusvirus replication proteins in yeast. Key role for the conserved Vps4p AAA ATPase, whose canonical function is to disassemble the ESCRT complexes, i.e. endosomal sorting complexes required for transport, and recycle them from the membranes back to the cytosol. Vps4p is recruited to become a permanent component of the viral replicase complexes, it is co-localized with the viral dsRNA and contacts the viral (+)RNA in the intracellular membrane
physiological function
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subunit ATP6V0D2 is a key component of macrophage-specific autophagosome-lysosome fusion machinery maintaining macrophage organelle homeostasis and, in turn, limiting both inflammation and bacterial infection. The enzyme subunit Atp6v0d2 inhibits inflammasome-dependent colitis. Subunit ATP6V0D1 but not ATP6V0D2 is required for lysosome acidification and maturation in macrophages. Subunit ATP6V0D2, but not ATP6V0D1, forms a complex with VAMP8 and STX17, and is required for the optimal stabilization of this complex in activated macrophages
physiological function
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the enzyme is intimately associated with the ESCRT machinery and is essential for the membrane scission cycle. The enzyme is recruited to scission sites by Vps2. By recycling Vps2, the enzyme promotes Snf7 polymerization. Thus, the enzyme is critical for the recycling of ESCRT-III and the replenishment of the soluble cytoplasmic pool
physiological function
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the enzyme remodels and disassembles endosomal sorting complex required for transport III
physiological function
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the enzyme remodels different endosomal sorting complex required for transport-III filaments or tubular structures. The enzyme catalyzes constriction of CHMP2A-3 tubular filaments leading to membrane constriction
physiological function
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the enzyme provides energy for the ESCRT (endosomal sorting complexes required for transport) pathway
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physiological function
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Vps4p is required for the formation of spherule-like structures induced by tombusvirus replication proteins in yeast. Key role for the conserved Vps4p AAA ATPase, whose canonical function is to disassemble the ESCRT complexes, i.e. endosomal sorting complexes required for transport, and recycle them from the membranes back to the cytosol. Vps4p is recruited to become a permanent component of the viral replicase complexes, it is co-localized with the viral dsRNA and contacts the viral (+)RNA in the intracellular membrane
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additional information
UBX-domain containing Dictyostelium protein UBXD9 is identified as p97 interaction partner. Dictyostelium UBXD9 protein disassembles wild-type, but to a lesser extent mutant, p97 hexamers very efficiently into monomers. Enzyme p97 structure homology modelling using the crystal structure of mouse p97 (PDB entry 3cf2) as template
additional information
UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner. Human UBXD9 protein disassembles wild-type, but to a lesser extent mutant, p97 hexamers very efficiently into monomers. Enzyme p97 structure homology modelling using the crystal structure of mouse p97 (PDB entry 3cf2) as template
additional information
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UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner. Human UBXD9 protein disassembles wild-type, but to a lesser extent mutant, p97 hexamers very efficiently into monomers. Enzyme p97 structure homology modelling using the crystal structure of mouse p97 (PDB entry 3cf2) as template