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Information on EC 7.1.2.2 - H+-transporting two-sector ATPase and Organism(s) Homo sapiens

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IUBMB Comments
A multisubunit non-phosphorylated ATPase that is involved in the transport of ions. Large enzymes of mitochondria, chloroplasts and bacteria with a membrane sector (Fo, Vo, Ao) and a cytoplasmic-compartment sector (F1, V1, A1). The F-type enzymes of the inner mitochondrial and thylakoid membranes act as ATP synthases. All of the enzymes included here operate in a rotational mode, where the extramembrane sector (containing 3 alpha- and 3 beta-subunits) is connected via the delta-subunit to the membrane sector by several smaller subunits. Within this complex, the gamma- and epsilon-subunits, as well as the 9--12 c subunits rotate by consecutive 120_degree_ angles and perform parts of ATP synthesis. This movement is driven by the H+ electrochemical potential gradient. The V-type (in vacuoles and clathrin-coated vesicles) and A-type (archaeal) enzymes have a similar structure but, under physiological conditions, they pump H+ rather than synthesize ATP.
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
atp synthase, v-atpase, f1-atpase, h+-atpase, mitochondrial atpase, vacuolar h(+)-atpase, vacuolar atpase, lipid-binding protein, vacuolar h+-atpase, f0f1-atpase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 kDa mediatophore protein
-
-
-
-
32 kDa accessory protein
-
-
-
-
59 kDa membrane-associated GTP-binding protein
-
-
-
-
A6L
-
-
-
-
ATP synthase
ATP synthase proteolipid P1
-
-
-
-
ATP synthase proteolipid P2
-
-
-
-
ATP synthase proteolipid P3
-
-
-
-
ATP5alpha1
-
subunit
bacterial Ca2+/Mg2+ ATPase
-
-
-
-
BN59
-
-
-
-
C7-1 protein
-
-
-
-
CGI-11
-
-
-
-
chloroplast ATPase
-
-
-
-
coupling factors (F0,F1 and CF1)
-
-
-
-
Dicyclohexylcarbodiimide-binding protein
-
-
-
-
Ductin
-
-
-
-
DVA41
-
-
-
-
Ecto-F1Fo ATP synthase/F1 ATPase
-
-
F-type proton-translocating ATPase
-
-
F0F1-ATPase
-
-
-
-
F1-ATPase
F1-F0 ATP synthase
-
-
F1F0 ATPase
-
-
-
-
F1F0H+-ATPase
-
-
-
-
F1FO-ATP synthase
-
-
F1FO-ATPase
-
-
FoF1 ATP synthase
-
-
H+-ATPase
-
-
-
-
H+-translocating ATPase
-
-
-
-
H+-transporting ATPase
-
-
-
-
HATPL
-
-
-
-
HO57
-
-
-
-
Invasion protein invC
-
-
-
-
Isoform HO68
-
-
-
-
Isoform VA68
-
-
-
-
Lipid-binding protein
-
-
-
-
M40
-
-
-
-
matpase
-
-
mitochondrial ATPase
-
-
-
-
mitochondrial F1Fo-ATP synthase
-
-
mitochondrial H+-ATP synthase
-
-
My032 protein
-
-
-
-
Oligomycin sensitivity conferral protein
-
-
-
-
OSCP
-
-
-
-
P31
-
-
-
-
P39
-
-
-
-
Physophilin
-
-
-
-
PKIWI505
-
-
-
-
Protein bellwether
-
-
-
-
Sul-ATPase alpha
-
-
-
-
Sul-ATPase beta
-
-
-
-
SUL-ATPase epsilon
-
-
-
-
Sul-ATPase gamma
-
-
-
-
UV-inducible PU4 protein
-
-
-
-
V-ATPase
-
-
V-ATPase 28 kDa accessory protein
-
-
-
-
V-ATPase 40 kDa accessory protein
-
-
-
-
V-ATPase 41 KDa accessory protein
-
-
-
-
V-ATPase 9.2 kDa membrane accessory protein
-
-
-
-
V-ATPase S1 accessory protein
-
-
-
-
vacuolar H+-ATPase
-
-
VEG100
-
-
-
-
VEG31
-
-
-
-
Vegetative protein 100
-
-
-
-
Vegetative protein 31
-
-
-
-
VHA16K
-
-
-
-
YOPS secretion ATPase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + 4 H+[side 1] = ADP + phosphate + 4 H+[side 2]
show the reaction diagram
catalytic mechanism of the enzyme complex
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (H+-transporting)
A multisubunit non-phosphorylated ATPase that is involved in the transport of ions. Large enzymes of mitochondria, chloroplasts and bacteria with a membrane sector (Fo, Vo, Ao) and a cytoplasmic-compartment sector (F1, V1, A1). The F-type enzymes of the inner mitochondrial and thylakoid membranes act as ATP synthases. All of the enzymes included here operate in a rotational mode, where the extramembrane sector (containing 3 alpha- and 3 beta-subunits) is connected via the delta-subunit to the membrane sector by several smaller subunits. Within this complex, the gamma- and epsilon-subunits, as well as the 9--12 c subunits rotate by consecutive 120_degree_ angles and perform parts of ATP synthesis. This movement is driven by the H+ electrochemical potential gradient. The V-type (in vacuoles and clathrin-coated vesicles) and A-type (archaeal) enzymes have a similar structure but, under physiological conditions, they pump H+ rather than synthesize ATP.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + H2O + 4 H+[side 1]
ADP + phosphate + 4 H+[side 2]
show the reaction diagram
ATP + H2O + H+/in
ADP + phosphate + H+/out
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O + 4 H+[side 1]
ADP + phosphate + 4 H+[side 2]
show the reaction diagram
ATP + H2O + H+/in
ADP + phosphate + H+/out
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATPase inhibitor factor 1
-
i.e. IF1, intrinsic peptide inhibitor, up-regulated in human breast, colon and lung carcinomas. The binding of IF1 to beta-F1-ATPase is regulated by the energetic state of mitochondria. siRNA-mediated silencing of IF1 in cells expressing high levels of IF1 triggers the down-regulation of aerobic glycolysis and an increase in the activity of the H+-ATP synthase
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BTB06584
-
-
iejimalide A
-
a macrolide that is cytostatic or cytotoxic against a wide range of cancer cells at low nanomolar concentrations, inhibits vacuolar H+-ATPase in the context of epithelial tumor cells leading to a lysosome-initiated cell death process, overview
iejimalide B
-
a macrolide that is cytostatic or cytotoxic against a wide range of cancer cells at low nanomolar concentrations, inhibits vacuolar H+-ATPase in the context of epithelial tumor cells leading to a lysosome-initiated cell death process, overview
IF1 protein
-
the ability of IF1 to inhibit F1-ATPase activity depends on pH with a better efficiency at pH below 6.5
-
IF1-H49K protein
-
the F1-ATpase specific inhibitor inhibits the ATPase activity, the IF1 mutant shows inhibitory activity at neutral pH
-
oligomycin
-
-
peptide IF1
-
a natural inhibitor of the F1-ATPase, which binds at acidic pH, at cell surfaces
-
additional information
-
both inhibitors, iejimalides A and B, sequentially neutralize the pH of lysosomes, induce S-phase cell-cycle arrest, and trigger apoptosis in MCF-7 cells, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
apoA-I
-
the enzyme binds apoA-I which activates the ATPase activity. The antiapoptotic and proliferative effects of apoA-I on HUVECs are totally blocked by the F1-ATPase ligands IF1-H49K, angiostatin and anti-F1-ATPase antibody, independently of the scavenger receptor SR-BI and ABCA1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
vacuolar H+-ATPase
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
detergent-resistant membrane microdomains enriched in cholesterol and sphingolipid, association with F1-ATPase, overview
-
Manually annotated by BRENDA team
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vacuolar H+-ATPase
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
repression of the bioenergetic function of mitochondria is one of the strategies of the cancer cell in order to ensure its proliferation by diminishing the potential to execute ROS-mediated cell death
physiological function
additional information
-
expression of the catalytic subunit beta-F1-ATPase is tightly regulated at post-transcriptional levels during mammalian development and in the cell cycle. Downregulation of beta-F1-ATPase is a hallmark of most human carcinomas. Role of the ATPase inhibitor factor 1 and of Ras-GAP SH3 binding protein 1, G3BP1, controlling the activity of the H+-ATP synthase and the translation of beta-F1-ATPase mRNA respectively in cancer cells. A trans-acting factor that regulate beta-F1-ATPasemRNA translation, is G3BP1, Ras-GAP SH3 binding protein 1, that interacts with the 3'UTR of beta-mRNA, the interaction specifically represses mRNA translation by preventing its recruitment into active polysomes
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ATPB_HUMAN
529
0
56560
Swiss-Prot
Mitochondrion (Reliability: 1)
VATA_HUMAN
617
0
68304
Swiss-Prot
other Location (Reliability: 1)
V9HW31_HUMAN
529
0
56560
TrEMBL
Mitochondrion (Reliability: 1)
B7Z2V6_HUMAN
334
0
37751
TrEMBL
other Location (Reliability: 1)
H0YH81_HUMAN
362
0
38250
TrEMBL
Mitochondrion (Reliability: 2)
Q0QEN7_HUMAN
445
0
48113
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
phylogenetic analysis of the homologous F0F1-ATPases of bacteria, chloroplasts and mitochondria
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K212Q
-
site-directed mutagenesis for generation of mutation F1betaK212Q
additional information
-
siRNA-mediated downregulation of the beta subunit of the F1Fo-ATPase
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of Atp6p in HeLa cells depleted of the F1 beta subunit. Instead of being translationally downregulated, HeLa cells lacking F1 degrade Atp6p, thereby preventing proton leakage across the inner membrane
-
expression of C-terminally c-Myc-tagged wild-type F1b eta or F1betaK212Q mutants in HEK-293 cells
-
transient expression of GFP-tagged ATP5B protein on cell surface and mitochondria in carcinoma cell lines, i.e. Hep-G2 cells, A-549 cells, 95-D cells, L-02 cells, and HEK-293 cells, the ectopic expression of ATP synthase is a consequence of translocation from the mitochondria
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of the catalytic subunit beta-F1-ATPase is tightly regulated at post-transcriptional levels during mammalian development and in the cell cycle
-
repression of beta-F1-ATPase expression in development and in cancer, translational silencing is usually mediated by 3'UTR-mediated sequestration of the mRNA into RNPs. Role of ATPase inhibitor factor 1 and of Ras-GAP SH3 binding protein 1, G3BP1, controlling the activity of the H+-ATP synthase and the translation of beta-F1-ATPase mRNA respectively in cancer cells. A trans-acting factor that regulate beta-F1-ATPase mRNA translation, is G3BP1, Ras-GAP SH3 binding protein 1, that interacts with the 3'UTR of beta-mRNA, the interaction specifically represses mRNA translation by preventing its recruitment into active polysomes
-
X-ray radiation enhances gene expression in mRNA and protein level of subunit ATP5alpha1
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Blair, A.; Ngo, L.; Park, J.; Paulsen, I.T.; Saier, M.H.
Phylogenetic analyses of the homologous transmembrane channel-forming proteins of the F0F1-ATPases of bacteria, chloroplasts and mitochondria
Microbiology
142
17-32
1996
Anabaena sp., Apis mellifera, Ascaris suum, Aspergillus nidulans, Cytobacillus firmus, Priestia megaterium, Balaenoptera physalus, Beta vulgaris, Bos taurus, Brassica napus, Saccharomyces cerevisiae, Caenorhabditis elegans, Candida parapsilosis, Cyprinus carpio, Cricetulus griseus, Bipolaris maydis, Cricetulus sp., Drosophila melanogaster, Escherichia coli, Euglena gracilis, Homo sapiens, Locusta migratoria, Marchantia polymorpha, Mus musculus, Neurospora crassa, Nicotiana tabacum, Trieres chinensis, Oenothera berteroana, Oryza sativa, Paracentrotus lividus, Phoca vitulina, Pisaster ochraceus, Pisum sativum, Podospora anserina, Propionigenium modestum, Rattus norvegicus, Rhodospirillum rubrum, Schizosaccharomyces pombe, Spinacia oleracea, Synechococcus sp., Bacillus sp. PS3, Triticum aestivum, Trypanosoma brucei, Vibrio alginolyticus, Xenopus laevis, Zea mays
Manually annotated by BRENDA team
Champagne, E.; Martinez, L.O.; Collet, X.; Barbaras, R.
Ecto-F1Fo ATP synthase/F1 ATPase: metabolic and immunologic functions
Curr. Opin. Lipidol.
17
279-284
2006
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Radojkovic, C.; Genoux, A.; Pons, V.; Combes, G.; de Jonge, H.; Champagne, E.; Rolland, C.; Perret, B.; Collet, X.; Terce, F.; Martinez, L.O.
Stimulation of cell surface F1-ATPase activity by apolipoprotein A-I inhibits endothelial cell apoptosis and promotes proliferation
Arterioscler. Thromb. Vasc. Biol.
29
1125-1130
2009
Homo sapiens
Manually annotated by BRENDA team
McHenry, P.; Wang, W.L.; Devitt, E.; Kluesner, N.; Davisson, V.J.; McKee, E.; Schweitzer, D.; Helquist, P.; Tenniswood, M.
Iejimalides A and B inhibit lysosomal vacuolar H+-ATPase (V-ATPase) activity and induce S-phase arrest and apoptosis in MCF-7 cells
J. Cell. Biochem.
109
634-642
2010
Homo sapiens
Manually annotated by BRENDA team
Ma, Z.; Cao, M.; Liu, Y.; He, Y.; Wang, Y.; Yang, C.; Wang, W.; Du, Y.; Zhou, M.; Gao, F.
Mitochondrial F1Fo-ATP synthase translocates to cell surface in hepatocytes and has high activity in tumor-like acidic and hypoxic environment
Acta Biochim. Biophys. Sin. (Shanghai)
42
530-537
2010
Homo sapiens
Manually annotated by BRENDA team
Willers, I.M.; Cuezva, J.M.
Post-transcriptional regulation of the mitochondrial H+-ATP synthase: a key regulator of the metabolic phenotype in cancer
Biochim. Biophys. Acta
1807
543-551
2011
Saccharomyces cerevisiae, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Rak, M.; McStay, G.P.; Fujikawa, M.; Yoshida, M.; Manfredi, G.; Tzagoloff, A.
Turnover of ATP synthase subunits in F1-depleted HeLa and yeast cells
FEBS Lett.
585
2582-2586
2011
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Gorai, T.; Goto, H.; Noda, T.; Watanabe, T.; Kozuka-Hata, H.; Oyama, M.; Takano, R.; Neumann, G.; Watanabe, S.; Kawaoka, Y.
F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding
Proc. Natl. Acad. Sci. USA
109
4615-4620
2012
Homo sapiens
Manually annotated by BRENDA team
Ito, Y.; Ikeguchi, M.
Mechanism of the alphabeta conformational change in F1-ATPase after ATP hydrolysis: free-energy simulations
Biophys. J.
108
85-97
2015
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Kowalski-Chauvel, A.; Najib, S.; Tikhonova, I.G.; Huc, L.; Lopez, F.; Martinez, L.O.; Cohen-Jonathan-Moyal, E.; Ferrand, A.; Seva, C.
Identification of the F1-ATPase at the cell surface of colonic epithelial cells: role in mediating cell proliferation
J. Biol. Chem.
287
41458-41468
2012
Homo sapiens
Manually annotated by BRENDA team
Zhdanov, A.V.; Andreev, D.E.; Baranov, P.V.; Papkovsky, D.B.
Low energy costs of F1Fo ATP synthase reversal in colon carcinoma cells deficient in mitochondrial complex IV
Free Radic. Biol. Med.
106
184-195
2017
Homo sapiens
Manually annotated by BRENDA team
Wang, Y.; Hou, Q.; Xiao, G.; Yang, S.; Di, C.; Si, J.; Zhou, R.; Ye, Y.; Zhang, Y.; Zhang, H.
Selective ATP hydrolysis inhibition in F1Fo ATP synthase enhances radiosensitivity in non-small-cell lung cancer cells (A549)
Oncotarget
8
53602-53612
2017
Homo sapiens
Manually annotated by BRENDA team