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Information on EC 3.6.4.6 - vesicle-fusing ATPase and Organism(s) Homo sapiens
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3.6.4.6 vesicle-fusing ATPaseIUBMB Comments
A large family of ATP-hydrolysing enzymes involved in the heterotypic fusion of membrane vesicles with target membranes and the homotypic fusion of various membrane compartments. They belong to the AAA-type (_A_TPase _a_ssociated with a variety of cell _a_ctivities) ATPase superfamily. They include peroxin, which apparently is involved in Zellweger's syndrome.
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Word Map
- 3.6.4.6
- snare
-
exocytosis
- syntaxins
- synaptic
- proteasome
-
disassembly
- snap-25
- endosomal
-
neurotransmitter
-
vesicle-associated
-
traffic
-
t-snares
- synaptobrevin
-
presynaptic
- atpases
-
neurotoxin
-
escrt-iii
-
exocytic
-
synaptosome-associated
-
multivesicular
- synapses
-
er-associated
- vamp
-
escrts
- synaptotagmins
-
snare-mediated
- botulinum
-
homotypic
-
cargo
-
dc-stamp
-
reticulum-associated
- nfatc1
- tetanus
-
valosin-containing
-
rankl-induced
-
ampars
-
retrotranslocation
-
four-helix
-
intra-golgi
-
fusogenic
-
neurosecretion
-
exocyst
-
3.6.1.3
-
autophagosome-lysosome
- peroxins
-
bonts
- medicine
- rab3a
-
tail-anchored
- oscar
-
ca2+-triggered
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
n-ethylmaleimide-sensitive factor, cdc48, aaa-atpase, n-ethylmaleimide-sensitive fusion protein, atp6v0d2, n-ethylmaleimide sensitive factor, sec18p, sec18, cdc48p, pex1p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
N-ethylmaleimide sensitive fusion protein
-
-
-
-
NEM-sensitive fusion protein
-
-
-
-
NSF protein
p97
SKD2 protein
-
-
-
-
Vesicular-fusion protein NSF
-
-
-
-
Vps4
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O = ADP + phosphate
large family of ATP-hydrolysing enzymes involved in the heterotypic fusion of membrane vesicles with target membranes and the homotypic fusion of various membrane compartments. They belong to the AAA-type (ATPase associated with a variety of cell activities) ATPase superfamily. They include peroxin, which apparently is involved in Zellweger 's syndrome.
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (vesicle-fusing)
A large family of ATP-hydrolysing enzymes involved in the heterotypic fusion of membrane vesicles with target membranes and the homotypic fusion of various membrane compartments. They belong to the AAA-type (_A_TPase _a_ssociated with a variety of cell _a_ctivities) ATPase superfamily. They include peroxin, which apparently is involved in Zellweger's syndrome.
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
-
-
210576, 210577, 210578, 210580, 210581, 210583, 210585, 656661, 669490, 685048, 699411, 756027, 756698, 758466
-
-
?
ATP + H2O
ADP + phosphate
-
Pex1p possesses two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, possibly playing distinct functions in peroxisome biogenesis
-
-
?
additional information
?
-
UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner
-
-
-
additional information
?
-
-
UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
-
-
-
-
?
ATP + H2O
ADP + phosphate
-
Pex1p possesses two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, possibly playing distinct functions in peroxisome biogenesis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
Pex1p possesses two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, possibly playing distinct functions in peroxisome biogenesis
-
membrane, Pex1p possesses two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, possibly playing distinct functions in peroxisome biogenesis
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
additional information
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
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
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 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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). VPS4A_HUMAN
437
0
48898
Swiss-Prot
other Location (Reliability: 1)
NSF_HUMAN
744
0
82594
Swiss-Prot
other Location (Reliability: 3)
TERA_HUMAN
806
0
89322
Swiss-Prot
other Location (Reliability: 1)
VPS4B_HUMAN
444
0
49302
Swiss-Prot
other Location (Reliability: 2)
A8K5D8_HUMAN
444
0
49231
TrEMBL
other Location (Reliability: 2)
I3L4J1_HUMAN
428
0
48071
TrEMBL
other Location (Reliability: 2)
A0A7P0T8A3_HUMAN
760
0
84384
TrEMBL
other Location (Reliability: 2)
Q96D47_HUMAN
326
0
36210
TrEMBL
other Location (Reliability: 2)
I3L2G1_HUMAN
136
0
15216
TrEMBL
other Location (Reliability: 2)
A0A024R2C5_HUMAN
444
0
49302
TrEMBL
other Location (Reliability: 2)
B7Z5J7_HUMAN
739
0
82058
TrEMBL
other Location (Reliability: 1)
A0A7I2V540_HUMAN
804
0
89097
TrEMBL
other Location (Reliability: 1)
A0A7I2V5G8_HUMAN
334
0
37115
TrEMBL
other Location (Reliability: 1)
B7Z9U2_HUMAN
650
0
72228
TrEMBL
other Location (Reliability: 1)
I3L0N3_HUMAN
739
0
82092
TrEMBL
other Location (Reliability: 1)
K7EQD6_HUMAN
180
0
20089
TrEMBL
other Location (Reliability: 3)
A0A6Q8PGU6_HUMAN
916
0
100350
TrEMBL
Mitochondrion (Reliability: 3)
D3DXJ4_HUMAN
278
0
31101
TrEMBL
other Location (Reliability: 1)
A0A7P0T8Q5_HUMAN
754
0
83409
TrEMBL
other Location (Reliability: 1)
C9JUP7_HUMAN
761
0
84513
TrEMBL
other Location (Reliability: 2)
I3L0L3_HUMAN
161
0
17980
TrEMBL
other Location (Reliability: 1)
A0A7P0TAQ1_HUMAN
733
0
80608
TrEMBL
other Location (Reliability: 1)
Q9HAP1_HUMAN
307
0
34392
TrEMBL
other Location (Reliability: 1)
A0A7P0TAW3_HUMAN
772
0
86119
TrEMBL
other Location (Reliability: 1)
B4DSK5_HUMAN
703
0
77961
TrEMBL
Mitochondrion (Reliability: 2)
B4DH19_HUMAN
650
0
72259
TrEMBL
other Location (Reliability: 1)
B4DGR3_HUMAN
702
0
77877
TrEMBL
other Location (Reliability: 3)
A0A024R705_HUMAN
437
0
48898
TrEMBL
other Location (Reliability: 1)
A0A7I2V2Y2_HUMAN
458
0
50994
TrEMBL
other Location (Reliability: 1)
V9HW80_HUMAN
806
0
89322
TrEMBL
other Location (Reliability: 1)
A0A7P0Z4C6_HUMAN
694
0
76918
TrEMBL
other Location (Reliability: 1)
A0A384MTI6_HUMAN
744
0
82594
TrEMBL
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oligomer
-
Pex1p possesses two distinct oligomeric forms, a homo-oligomer in the cytosol and a hetero-oligomer on peroxisome membranes, possibly playing distinct functions in peroxisome biogenesis. Interaction of Pex1p with Pex6p confers a conformatinal and dissociation of the Pex1p oligomer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R155C
naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity, and a twofold decreased kd for human protein UBXD9
R155H
naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity, no change in the kd value for human protein UBXD9
R93C
naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity and a twofold increased kd for human protein UBXD9
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged wild-type and mutant p97s from Escherichia coli by glutathione affinity and cleavage of the tag by PreScission protease
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isolation of PEX2 and PEX6 cDNA, Pex1p expressed in wild-type chinese hamster ovary cells, CHO-K1
-
recombinant expression of GST-tagged wild-type and mutant p97 in Escherichia coli strain Arctic express RIL, coexpression with GST-tagged human UBXD9 protein in Escherichia coli in strain BL21Gold (DE3) pLysS
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
HsPEX1 is the causative gene for peroxisome-deficiency autosomal recessive disorders like cerebro-hepato-renal Zellweger syndrome, neonatal adrenoleukodystrophy and infantile refsum disease
medicine
-
diagnosis, HsPex6p mutations are one of the causes of Zellweger syndrome
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Confalonieri, F.; Duguet, M.
A 200-amino acid ATPase module in search of a basic function
Bioessays
17
639-650
1995
Saccharomyces cerevisiae, Candida albicans, Cricetulus longicaudatus, Drosophila melanogaster, Homo sapiens, Mus musculus, Sulfolobus acidocaldarius, Xenopus laevis
Finken-Eigen, M.; Roehricht, R.A.; Koehrer, K.
The VPS4 gene is involved in protein transport out of a yeast pre-vacuolar endosome-like compartment
Curr. Genet.
31
469-480
1997
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Schizosaccharomyces pombe
Babst, M.; Sato, T.K.; Banta, L.M.; Emr, S.D.
Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p
EMBO J.
16
1820-1831
1997
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Schizosaccharomyces pombe
Faber, K.N.; Heyman, J.A.; Subramani, S.
Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes
Mol. Cell. Biol.
18
936-943
1998
Homo sapiens, Komagataella pastoris
Tamura, S.; Shimozawa, N.; Suzuki, Y.; Tsukamoto, T.; Osumi, T.; Fujiki, Y.
A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p
Biochem. Biophys. Res. Commun.
245
883-886
1998
Homo sapiens, Rattus norvegicus
Imamura, A.; Tamura, S.; Shimozawa, N.; Suzuki, Y.; Zhang, Z.; Tsukamoto, T.; Orii, T.; Kondo, N.; Osumi, T.; Fujiki, Y.
Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders
Hum. Mol. Genet.
7
2089-2094
1998
Homo sapiens
Yoshimori, T.; Yamagata, F.; Yamamoto, A.; Mizushima, N.; Kabeya, Y.; Nara, A.; Miwako, I.; Ohashi, M.; Ohsumi, M.; Ohsumi, Y.
The mouse SKD1, a homologue of yeast Vps4p, is required for normal endosomal trafficking and morphology in mammalian cells
Mol. Biol.
11
747-763
2000
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Rattus norvegicus
Whiteheart, S.W.; Matveeva, E.A.
Multiple binding proteins suggest diverse functions for the N-ethylmaleimide sensitive factor
J. Struct. Biol.
146
32-43
2004
Homo sapiens
Tamura, S.; Yasutake, S.; Matsumoto, N.; Fujiki, Y.
Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p
J. Biol. Chem.
281
27693-27704
2006
Homo sapiens
Platta, H.W.; Debelyy, M.O.; El Magraoui, F.; Erdmann, R.
The AAA peroxins Pex1p and Pex6p function as dislocases for the ubiquitinated peroxisomal import receptor Pex5p
Biochem. Soc. Trans.
36
99-104
2008
Homo sapiens
Fisher, E.A.; Lapierre, L.R.; Junkins, R.D.; McLeod, R.S.
The AAA-ATPase p97 facilitates degradation of apolipoprotein B by the ubiquitin-proteasome pathway
J. Lipid Res.
49
2149-2160
2008
Homo sapiens
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
J. Biol. Chem.
287
5928-5941
2012
Homo sapiens
Caillat, C.; Maity, S.; Miguet, N.; Roos, W.H.; Weissenhorn, W.
The role of VPS4 in ESCRT-III polymer remodeling
Biochem. Soc. Trans.
47
441-448
2019
Homo sapiens
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
Eur. J. Cell Biol.
95
195-207
2016
Homo sapiens (P55072), Homo sapiens, Dictyostelium discoideum (Q75JI3)
Alonso Y Adell, M.; Migliano, S.M.; Teis, D.
ESCRT-III and Vps4 a dynamic multipurpose tool for membrane budding and scission
FEBS J.
283
3288-3302
2016
Homo sapiens
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