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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
-
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
-
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
-
subunit Atp6v0d2-deficient macrophages have augmented mitochondrial damage, enhanced inflammasome activation and reduced clearance of Salmonella typhimurium
malfunction
-
deletion of Vps4p in yeast leads to the formation of crescent-like membrane structures instead of the characteristic spherule and vesicle-like structures
-
metabolism
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
the enzyme remodels and disassembles endosomal sorting complex required for transport III
physiological function
-
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
-
the enzyme provides energy for the ESCRT (endosomal sorting complexes required for transport) pathway
-
physiological function
-
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
-
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
-
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
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Confalonieri, F.; Duguet, M.
A 200-amino acid ATPase module in search of a basic function
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1995
Saccharomyces cerevisiae, Candida albicans, Cricetulus longicaudatus, Drosophila melanogaster, Homo sapiens, Mus musculus, Sulfolobus acidocaldarius, Xenopus laevis
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Homo sapiens, Komagataella pastoris
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Komagataella pastoris
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2002
Saccharomyces cerevisiae
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2002
Rattus norvegicus
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2003
Saccharomyces cerevisiae
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Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B
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117
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2004
Mus musculus
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Analysis of the mutant Drosophila N-ethylmaleimide sensitive fusion-1 protein in comatose reveals molecular correlates of the behavioural paralysis
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2001
Drosophila melanogaster
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Multiple binding proteins suggest diverse functions for the N-ethylmaleimide sensitive factor
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146
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2004
Homo sapiens
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Distinct roles for the AAA ATPases NSF and p97 in the secretory pathway
Mol. Biol. Cell
15
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2004
Cricetulus griseus, Mus musculus
brenda
Liu, C.; Hu, B.
Alterations of N-ethylmaleimide-sensitive ATPase following transient cerebral ischemia
Neuroscience
128
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2004
Rattus norvegicus
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Littleton, J.T.; Barnard, R.J.; Titus, S.A.; Slind, J.; Chapman, E.R.; Ganetzky, B.
SNARE-complex disassembly by NSF follows synaptic-vesicle fusion
Proc. Natl. Acad. Sci. USA
98
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2001
Drosophila melanogaster
brenda
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Crystallographic characterization of the N-terminal domain of PEX1
Acta Crystallogr. Sect. D
60
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2004
Mus musculus
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Presence of N-ethyl maleimide sensitive factor (NSF) on the acrosome of mammalian sperm
Arch. Androl.
50
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2004
Bos taurus, Mus musculus
brenda
Fan, W.; Fujiki, Y.
A temperature-sensitive CHO pex1 mutant with a novel mutation in the AAA Walker A1 motif
Biochem. Biophys. Res. Commun.
345
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2006
Cricetulus griseus
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Comparative analysis of expression of two p97 homologues in Caenorhabditis elegans
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345
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2006
Caenorhabditis elegans
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A novel member of the NSF family in the corn earworm, Helicoverpa zea: molecular cloning, developmental expression, and tissue distribution
Biochim. Biophys. Acta
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2006
Helicoverpa zea
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nsf is essential for organization of myelinated axons in zebrafish
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2006
Danio rerio
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N-ethylmaleimide sensitive factor is required for fusion of the C. elegans uterine anchor cell
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Caenorhabditis elegans
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Coordinated action of NSF and PKC regulates GABAB receptor signaling efficacy
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2006
Rattus norvegicus
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The beta domain is required for Vps4p oligomerization into a functionally active ATPase
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Saccharomyces cerevisiae
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A genetic screen for suppressors of Drosophila NSF2 neuromuscular junction overgrowth
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170
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2005
Drosophila sp. (in: flies)
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Helicoverpa armigera
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Homo sapiens
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Rattus norvegicus
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Mus musculus
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Caenorhabditis elegans
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Proc. Natl. Acad. Sci. USA
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Mus musculus
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Homo sapiens
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Rattus norvegicus
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A search for synthetic peptides that inhibit soluble N-ethylmaleimide sensitive-factor attachment receptor-mediated membrane fusion
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Mus musculus
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Mammalia
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156
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Molecular characterization and functional distribution of N-ethylmaleimide-sensitive factor in Helicoverpa armigera
Peptides
27
1226-1234
2006
Helicoverpa armigera
brenda
Haas, T.J.; Sliwinski, M.K.; Martinez, D.E.; Preuss, M.; Ebine, K.; Ueda, T.; Nielsen, E.; Odorizzi, G.; Otegui, M.S.
The Arabidopsis AAA ATPase SKD1 is involved in multivesicular endosome function and interacts with its positive regulator lyst-interacting protein5
Plant Cell
19
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2007
Arabidopsis thaliana
brenda
Briggs, L.C.; Baldwin, G.S.; Miyata, N.; Kondo, H.; Zhang, X.; Freemont, P.S.
Analysis of nucleotide binding to p97 reveals the properties of a tandem AAA hexameric ATPase
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283
13745-13752
2008
Rattus norvegicus (P46462)
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The AAA-ATPase p97 facilitates degradation of apolipoprotein B by the ubiquitin-proteasome pathway
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49
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2008
Homo sapiens
brenda
Hartmann, C.; Chami, M.; Zachariae, U.; de Groot, B.L.; Engel, A.; Gruetter, M.G.
Vacuolar protein sorting: two different functional states of the AAA-ATPase Vps4p
J. Mol. Biol.
377
352-363
2008
Saccharomyces cerevisiae (P52917), Saccharomyces cerevisiae
brenda
Yu, Z.; Gonciarz, M.D.; Sundquist, W.I.; Hill, C.P.; Jensen, G.J.
Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p
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377
364-377
2008
Saccharomyces cerevisiae
brenda
Inoue, M.; Kamikubo, H.; Kataoka, M.; Kato, R.; Yoshimori, T.; Wakatsuki, S.; Kawasaki, M.
Nucleotide-dependent conformational changes and assembly of the AAA ATPase SKD1/VPS4B
Traffic
9
2180-2189
2008
Mus musculus (P46467)
brenda
Naydenov, N.G.; Harris, G.; Brown, B.; Schaefer, K.L.; Das, S.K.; Fisher, P.B.; Ivanov, A.I.
Loss of soluble N-ethylmaleimide-sensitive factor attachment protein alpha (alphaSNAP) induces epithelial cell apoptosis via down-regulation of Bcl-2 expression and disruption of the Golgi
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287
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2012
Homo sapiens
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Cricetinae
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae, Saccharolobus solfataricus (Q97ZJ7), Saccharolobus solfataricus, Saccharolobus solfataricus P2 (Q97ZJ7)
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Legent, K.; Liu, H.H.; Treisman, J.E.
Drosophila Vps4 promotes epidermal growth factor receptor signaling independently of its role in receptor degradation
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Drosophila melanogaster (Q9Y162)
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Vivona, S.; Cipriano, D.J.; OLeary, S.; Li, Y.H.; Fenn, T.D.; Brunger, A.T.
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Cricetulus griseus
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Saccharomyces cerevisiae (P52917)
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Arabidopsis thaliana (Q9ZNT0)
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Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
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Homo sapiens
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Rijal, R.; Arhzaouy, K.; Strucksberg, K.; Cross, M.; Hofmann, A.; Schroeder, R.; Clemen, C.; Eichinger, L.
Mutant p97 exhibits species-specific changes of its ATPase activity and compromises the UBXD9-mediated monomerisation of p97 hexamers
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Homo sapiens (P55072), Homo sapiens, Dictyostelium discoideum (Q75JI3)
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Homo sapiens
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Tan, J.; Davies, B.A.; Payne, J.A.; Benson, L.M.; Katzmann, D.J.
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Saccharomyces cerevisiae
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Schoeneberg, J.; Pavlin, M.R.; Yan, S.; Righini, M.; Lee, I.H.; Carlson, L.A.; Bahrami, A.H.; Goldman, D.H.; Ren, X.; Hummer, G.; Bustamante, C.; Hurley, J.H.
ATP-dependent force generation and membrane scission by ESCRT-III and Vps4
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Homo sapiens
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