Any feedback?
Information on EC 7.2.2.19 - H+/K+-exchanging ATPase and Organism(s) Sus scrofa and UniProt Accession P19156
for references in articles please use BRENDA:EC7.2.2.19Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
7.2.2.19 H+/K+-exchanging ATPaseIUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. A gastric mucosal enzyme that catalyses the efflux of one H+ and the influx of one K+ per ATP hydrolysed.
Specify your search results
Word Map
- 7.2.2.19
-
parietal
- mucosa
- omeprazole
- stomach
- na,k-atpase
- alpha-subunits
- ulcer
- histamine
- beta-subunits
- helicobacter
- atpases
- gastritis
- pylori
- gastrin
-
antisecretory
-
basolateral
-
tubulovesicles
- reflux
- benzimidazole
- lansoprazole
-
oxyntic
- fundic
-
histamine-stimulated
- pepsinogen
-
k+-stimulated
-
pernicious
- cimetidine
-
k+-dependent
-
acid-related
-
h2-receptor
-
antiulcer
- rabeprazole
- pentagastrin
-
h-atpase
- phosphoenzyme
-
acid-secreting
-
tubulovesicular
-
hypergastrinemia
-
gastroprotective
-
bcecf
- ranitidine
-
canaliculus
-
ouabain-insensitive
-
pylorus-ligated
-
ion-transporting
- achlorhydria
-
thymectomy
- hypochlorhydria
- pharmacology
- medicine
-
14caminopyrine
-
zollinger-ellison
The taxonomic range for the selected organisms is: Sus scrofa
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
h,k-atpase, h+,k+-atpase, h+/k+-atpase, h(+),k(+)-atpase, h-k-atpase, h+-k+-atpase, gastric proton pump, gastric h,k-atpase, h+/k+ atpase, atp4a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(H++K+)-ATPase
-
-
-
-
H+,K+-ATPase
H+-K+-adenosinetriphosphatase
-
-
-
-
H+-K+-ATPase
H,K-ATPase
Proton pump
-
-
-
-
additional information
H+-K+-ATPase
-
-
-
-
H,K-ATPase
-
-
-
-
additional information
the enzyme belongs to the the cation-transporting P-type ATPase family
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + H+[side 1] + K+[side 2] = ADP + phosphate + H+[side 2] + K+[side 1]
orientation of the subunits in the membrane towards cytoplasmic and periplasmic sides and reaction mechanism, detailed overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type,H+/K+-exchanging)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. A gastric mucosal enzyme that catalyses the efflux of one H+ and the influx of one K+ per ATP hydrolysed.
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 + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
?
2'-deoxyATP + H2O + H+/in + K+/out
2'-deoxyADP + phosphate + H+/out + K+/in
-
37% of the activity with ATP
-
-
?
ADP + H2O + H+/in + K+/out
AMP + phosphate + H+/out + K+/in
-
7.5% of the activity with ATP
-
-
?
CTP + H2O + H+/in + K+/out
CDP + phosphate + H+/out + K+/in
-
13.2% of the activity with ATP
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
the electroneutral exchange of two cytoplasmic protons for two luminal potassium ions is achieved by the hydrolysis of one ATP molecule
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
-
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
protons are charge-transferred from the enzyme's alpha-subunit cytosolic side to H2O in sites 2 and 1, the H2O comes from cytosolic medium, and H3O+ in the sites are transported into lumen during the conformational transition from E1P to E2P, charge transfer pathway charge transfer pathway from hydronium ion in cytosolic medium to Glu345 in cation binding site 2: H3O+-Lys164-Gln161-Glu345
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the H,K-ATPase is the final step of acid secretion
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
The second ion species that can bind to the H,K-ATPase in the E1 conformation is K+ that competes with H+. Experimental activity measurement begins with the ion pump in the E1 state after treatment with nigericin
-
-
?
ATP + H2O + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
-
?
ATP + H2O + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
?
additional information
?
-
-
enzyme behaves as a passive cationic antiport in the absence of ATP
-
-
?
additional information
?
-
-
enzyme reconstituted into artificial phosphatidylcholine/cholesterol vesicles catalyzes an electroneutral H+-Rb+ exchange
-
-
?
additional information
?
-
-
the enzyme also performs K+-dependent NTP hydrolysis, utilizing ATP, GTP, CTP, UTP, and ITP, and an NTP/ADP exchange reaction, overview
-
-
?
additional information
?
-
-
a K+ efflux channel is associated with the gastric H,K-ATPase, KCNQ1-KCNE2 appears to be the K+ efflux channel that is essential for gastric acid secretion
-
-
?
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 + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
the electroneutral exchange of two cytoplasmic protons for two luminal potassium ions is achieved by the hydrolysis of one ATP molecule
-
-
?
ATP + H2O + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
?
additional information
?
-
-
a K+ efflux channel is associated with the gastric H,K-ATPase, KCNQ1-KCNE2 appears to be the K+ efflux channel that is essential for gastric acid secretion
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
-
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the H,K-ATPase is the final step of acid secretion
-
-
?
ATP + H2O + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
-
?
ATP + H2O + H+[side 1] + K+[side 2]
ADP + phosphate + H+[side 2] + K+[side 1]
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
K+
Mg2+
NH4+
Rb+
additional information
-
no protective effect during C12E8-solubilization of gastric H/K-ATPase by Na+ and Li+
K+
-
activates, with 0.11 mM as half saturating K+ concentration for both luminal binding sites, above 10 mM reduction of enzyme activity
K+
-
stabilizes both oligomeric assembly and enzyme activity in C12E8-solubilized gastric H/K-ATPase, 20-40 mM protects
K+
-
activates, required. But in the presence of 200m M KCl, ion binding sites are more than 99% saturated with K+. The enzyme activity under this condition is near zero
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-[(4-[4-[4-(azidomethyl)phenoxy]butoxy]-3-methylpyridin-2-yl)methanesulfinyl]-1H-benzimidazole
inhibits ATPase activity by approximately 50% at 0.01 mM
4-([2-[(1H-benzimidazole-2-sulfinyl)methyl]-3-methylpyridin-4-yl]oxy)butyl [4-(1,2,4,5-tetrazin-3-yl)phenyl]acetate
inhibits ATPase activity by approximately 50% at 0.01 mM
aluminum fluoride
reversible inhibition by the fluorinated phosphate analogue, activity is restored by divalent cations, e.g. Mg2+. Structural comparison of H+,K+-ATPase in the E2BeF and E2AlF states, overview
beryllium fluoride
irreversible inhibition by the fluorinated phosphate analogue, activity is not restored by divalent cations, e.g. Mg2+. Electronmicrospoic structure of BeF-bound H+,K+-ATPase at 8 A resolution, and structural comparison of H+,K+-ATPase in the E2BeF and E2AlF states, overview
magnesium fluoride
reversible inhibition by the fluorinated phosphate analogue, activity is restored by divalent cations, e.g. Mg2+
(7R,8R,9R)-2,3,10-trimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
-
(7R,8R,9R)-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
high-affinity K+-competitive inhibitor
(8-[(2-ethyl-6-methylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyrazin-6-yl)methanol
-
-
2-[5-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-7-yl]-4,5-dimethyl-1H-imidazole
-
-
2-{[3-(4,5-dimethyl-1H-imidazol-2-yl)-2',6'-dimethylbiphenyl-4-yl]oxy}acetamide
-
-
3-({[3-(4,5-dimethyl-1H-imidazol-2-yl)-2',6'-dimethylbiphenyl-4-yl]oxy}methyl)pyridine
-
-
8-[(2-ethyl-6-methylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
-
-
8-[(2-ethyl-6-methylbenzyl)amino]-N,2,3-trimethylimidazo[1,2-a]pyrazine-6-carboxamide
-
-
8-[(2-ethyl-6-methylbenzyl)amino]-N,N,2,3-tetramethylimidazo[1,2-a]pyrazine-6-carboxamide
-
-
8-[(2-ethyl-6-methylbenzyl)amino]-N-(2-hydroxyethyl)-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
-
-
8-[(2-ethyl-6-methylbenzyl)amino]-N-(2-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N,2,3-trimethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N-(1-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-7-methoxy-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
8-[[(1S,2S)-2-hydroxy-7-methyl-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
-
-
BYK73
i.e. (7R,8R,9R)-2,3,10-trimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
BYK99
i.e. (7R,8R,9R)-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol, high-affinity K+-competitive inhibitor
clotrimazole
-
molecular mechanism of the inhibitory effect is studied by steady-state fluorescence experiments with the electrochromic styryl dye RH421
Fluorescein 5'-isothiocyanate
-
fluorescein 5'-isothiocyanate modified enzyme has 0.5-1.5% residual ATPase activity compared to the unmodified enzyme
K+
-
activates, required. But in the presence of 200m M KCl, ion binding sites are more than 99% saturated with K+. The enzyme activity under this condition is near zero
methyl {[3-(4,5-dimethyl-1H-imidazol-2-yl)-2',6'-dimethylbiphenyl-4-yl]oxy}acetate
-
-
N-(2-ethyl-6-methylbenzyl)-2,3-dimethyl-6-(pyrrolidin-1-ylcarbonyl)imidazo[1,2-a]pyrazin-8-amine
-
-
N-(2-ethyl-6-methylbenzyl)-6-(methoxymethyl)-2,3-dimethylimidazo[1,2-a]pyrazin-8-amine
-
-
Omeprazole
-
no effect in the presence of K+ alone or NH4+. Inhibitory action can be fully reversed by addition of beta-mercaptoethanol
SCH28080
i.e. 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile
SCH28080
i.e., 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile
Trypsin
-
limited proteolysis, determination of peptide fragment sequences, overview
-
additional information
mechanism, by which divalent cations, e.g. Mg2+, reactivate the fluorinated phosphate analogue-inhibited H+,K+-ATPase. Mg2+ interacts with the outside of the vesicles, namely the cytoplasmic side of the enzyme, overview. Prevention of the Mg2+-induced reactivation by K+ binding. The magnitude of the Mg2+-induced reactivation is highly pH dependent, whereas the BeF-inhibited enzyme is not affected
-
additional information
-
development of 6-substituted imidazo[1,2-a]pyrazines inhibitors of the gastric H+/K+-ATPase, no inhibition by 8-[(2-ethyl-6-methylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
-
additional information
-
development of indanyl-substituted imidazo[1,2-a]pyridines as potent reversible inhibitors of the gastric H+/K+-ATPase, overview
-
additional information
-
pharmacophore modelling against known imidazopyridine and azaindole templates for detection and development of structure-based enzyme inhibitors, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no protective effect during C12E8-solubilization of gastric H/K-ATPase by choline
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0049
(7R,8R,9R)-2,3,10-trimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
wild type enzyme, at pH 7.6 and 37°C
0.0015
(7R,8R,9R)-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
wild type enzyme, at pH 7.6 and 37°C
0.0000058
8-(benzyloxy)-2-methylimidazo[1,2-a]pyridine
wild type enzyme, at pH 7.6 and 37°C
0.011
[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]acetonitrile
wild type enzyme, at pH 7.6 and 37°C
0.0032
[8-(benzyloxy)imidazo[1,2-a]pyridin-3-yl]acetonitrile
wild type enzyme, at pH 7.6 and 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.029
(7R,8R,9R)-2,3,10-trimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
Sus scrofa
wild type enzyme, at pH 7.6 and 37°C
0.000077
(7R,8R,9R)-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine-7,8-diol
Sus scrofa
wild type enzyme, at pH 7.6 and 37°C
0.0059
(8-[(2-ethyl-6-methylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyrazin-6-yl)methanol
Sus scrofa
-
pH 7.4, 22°C
0.11
8-(benzyloxy)-2-methylimidazo[1,2-a]pyridine
Sus scrofa
wild type enzyme, at pH 7.6 and 37°C
0.0055
8-[(2-ethyl-6-methylbenzyl)amino]-N,2,3-trimethylimidazo[1,2-a]pyrazine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0064
8-[(2-ethyl-6-methylbenzyl)amino]-N,N,2,3-tetramethylimidazo[1,2-a]pyrazine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.005
8-[(2-ethyl-6-methylbenzyl)amino]-N-(2-hydroxyethyl)-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.006
8-[(2-ethyl-6-methylbenzyl)amino]-N-(2-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0048
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0053
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N,2,3-trimethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0063
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0047
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-N-(1-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0057
8-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0057
8-[[(1S,2S)-2-hydroxy-7-methoxy-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0069
8-[[(1S,2S)-2-hydroxy-7-methyl-2,3-dihydro-1H-inden-1-yl]oxy]-N,N,2,3-tetramethylimidazo[1,2-a]pyridine-6-carboxamide
Sus scrofa
-
pH 7.4, 22°C
0.0069
N-(2-ethyl-6-methylbenzyl)-2,3-dimethyl-6-(pyrrolidin-1-ylcarbonyl)imidazo[1,2-a]pyrazin-8-amine
Sus scrofa
-
pH 7.4, 22°C
0.0055
N-(2-ethyl-6-methylbenzyl)-6-(methoxymethyl)-2,3-dimethylimidazo[1,2-a]pyrazin-8-amine
Sus scrofa
-
pH 7.4, 22°C
0.011
[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]acetonitrile
Sus scrofa
wild type enzyme, at pH 7.6 and 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.641
-
ATP hydrolysis in presence of 10 mM K+, 0.1 mM ADP, and 0.003 mM valinomycin
6.3
-
purified enzyme, 40 mM HEPES/Tris, 10 mM KCl, 2 mM MgCl2, 25 mM sucrose, 0.1 mM EGTA/Tris, 2 mM ATP/Tris pH 7.0, at 37°C
7.5
-
purified enzyme, 40 mM HEPES/Tris, 10 mM KCl, 2 mM MgCl2, 25 mM sucrose, 0.1 mM EGTA/Tris, 2 mM ATP/Tris pH 7.0, at 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 8.5
-
at pH 6.5 30% and at pH 8.5 less than 1% of all binding sites are occupied by H+ ions
6.8 - 7.8
-
pH 6.8: about 60% of maximal activity, pH 7.8: about 45% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
tubulovesicle membranes, H+,K+-ATPase is the most representative protein with 85%
-
LLC-PK1 cells stably expressing alpha- and beta subunits of the gatric H+,K+-ATPase
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
-
gastric vesicles are prepared from mucosa in the fundic region of hog stomaches
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the gastric proton pump, H+,K+-ATPase is the major membrane protein responsible for the gastric acid H+ secretion
physiological function
-
H+,K+-ATPase is responsible for the acidification of the gastric fluid
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). ATP4A_PIG
1034
8
114287
Swiss-Prot
other Location (Reliability: 1), other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterodimer
-
alphabeta structure, determination of the primary structure of the gastric H,K-ATPase alpha subunit containing the catalytic site, sequence comparison
additional information
additional information
-
homology modeling of wild-type and mutant gastric H+,K+-ATPase beta-subunit and molecular dynamics simulation, simulations of charge transfer in wild-type and mutant enzymes, structure comparisons, overview
additional information
-
a cluster of intramembranal carboxylic amino acids is located in the middle of the transmembrane segments TM4, TM5,TM6, and TM8 of the alpha-subunit that contains the ion binding domain in this enzyme and the ATPase
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
the beta-subunit contains five asparagine-linked oligosaccharide chains
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
AlFxADP bound enzyme form, beta-octyl glycoside-solubilized enzyme from SDS-purified membranes by 2D crystallization, dialysis for 12 h to 2 days in presence of Mg2+, glycerol and/or propionate in different compositions, structure determination and analysis by cryoelectron microscopy of the 2D samples, resolution of 14 A
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D136A
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
D136F
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
D136I
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
D136L
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
D137A
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, BYK99 and BYK73)
D137F
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-CN-, BYK99 and BYK73)
D137I
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, and BYK99)
D137L
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
D138I
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
E345D
-
site-directed mutagenesis, the mutant shows no charge transport pathway, the mutant shows unaltered cell surface expression compared to the wild-type enzyme
E345L
-
site-directed mutagenesis, the mutant shows no charge transport pathway, the mutant shows unaltered cell surface expression compared to the wild-type enzyme
E345Q
-
site-directed mutagenesis, the mutant shows an alternative charge transport pathway H3O+-Arg105-Gln161-Gln345, the mutant shows unaltered cell surface expression compared to the wild-type enzyme
E795Q
-
the mutant shows increased affinity for K+ compared to the wild type enzyme
E820Q
-
the mutant has K+-independent constitutive dephosphorylation activity and an increased preference for the E1 conformation
K164L
-
site-directed mutagenesis, the mutant shows an alternative charge transport pathway H3O+-Gln161-Glu345, the mutant shows unaltered cell surface expression compared to the wild-type enzyme
K791S
-
the mutation greatly reduces enzyme activity as well as increases the Ki for SCH28080
L139A
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
L139F
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
L139I
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
L141I
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
N138A
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
N138F
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
N138L
the mutant shows strongly increased sensitivity against imidazo[1,2-a]pyridine inhibitors (BYK99 and BYK73)
Q161L
-
site-directed mutagenesis, the mutant shows no charge transport pathway, the mutant shows unaltered cell surface expression compared to the wild-type enzyme
Y140A
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
Y140F
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
Y140I
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
Y140L
the mutant shows wild type-like sensitivity against imidazo[1,2-a]pyridine inhibitors (SCH28080, SCH-Me-, SCH-CN-, BYK99 and BYK73)
additional information
additional information
-
chimera of the NH2-terminal half of the rat gastric H,K-ATPase and the COOH-terminal half of the rat Na,K-ATPase behaves as a functional ion pump and indicates that the protein domains involved in cardiac glycoside binding are not confined to the amino-terminal half of the Na,K-ATPase
additional information
-
mutations towards the exoplasmic surface of TM4, TM5, TM6, the loop between TM5 and TM6, and one site at the end of TM8 altered either the Ki or change the nature of inhibition from strictly competitive to mixed or even non-competitive without affecting ion affinity
additional information
-
the fluorescence probe FITC preferentially forms a covalent bond with the epsilon-amino group of the Lys-518 residue, which is embedded in the conserved Lys-518 in the ATP binding site of the N domain. This chemical modification of the Lys residue impairs H+,K+-ATPase activity (1.7% of activity compared with that of mock-treated enzyme) due to a loss of ATP-binding ability
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
solubilization at pH 4.0 causes rapid loss of ATPase activity, probably due to an increased protease activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native gastric H+,K+-ATPase partially by enzyme-enriched membrane vesicle preparation using SDS or/and beta-octyl glycoside
-
native gastric H,K-ATPase from gastric mucosa by a method involving differential and density gradient centrifugation, e.g. sucrose step gradient centrifugation, and plasma vesicle formation oriented as in the parietal cell with the cytoplasmic side outward
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in HEK-293 cells, expression analysis, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
-
lower concentration of [(dihydroindenyl)oxy]acetic acid should be used for evaluation of the activity of K+-Cl- cotranporter without affecting the activities of coexisting Na+,K+-ATPase and H+,K+-ATPase in cells
additional information
additional information
-
binding and release steps of K+ and H+ in both principal conformations of the ion pump, E1 and P-E2, are electrogenic, whereas the conformation transitions do not contribute significantly to a charge movement wihtin the membrane dielectric
additional information
-
infrared spectra on multilayer stacks of native gastric tubulovesicle membranes, membrane tilt does not significantly contribute to the infrared dichroism, even for the largest thicknesses tested
additional information
-
strong evidence that the catalytic unit of C12E8-solubilized gastric H/K-ATPase is a tetraprotomer
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lacapere, J.J.; Robert, J.C.; Thomas-Soumarmon, A.
Efficient solubilization and purification of the gastric H+,K+-ATPase for functional and structural studies
Biochem. J.
345
239-245
2000
Sus scrofa
Xian, Y.; Hebert, H.
Three-dimensional structure of the porcine gastric H,K-ATPase from negatively stained crystals
J. Struct. Biol.
118
169-177
1997
Sus scrofa
Hebert, H.; Xian, Y.; Hacksell, I.; Mardh, S.
Two-dimensional crystals of membrane-bound gastric H,K-ATPase
FEBS Lett.
299
159-162
1992
Sus scrofa
Hango, T.; Nojima, S.; Setaka, M.
Purification and characterization of (H+ + K+)-ATPase from hog gastric mucosa
Jpn. J. Pharmacol.
52
295-305
1990
Sus scrofa
Okamoto, C.T.; Karpilow, J.M.; Smolka, A.; Forte, J.G.
Isolation and characterization of gastric microsomal glycoproteins. Evidence for a glycosylated beta-subunit of the H+/K+-ATPase
Biochim. Biophys. Acta
1037
360-372
1990
Sus scrofa
Callaghan, J.M.; Toh, B.H.; Simpson, R.J.; Baldwin, G.S.
Rapid purification of the gastric H+/K+-ATPase complex by tomato-lectin affinty chromatography
Biochem. J.
283
63-68
1992
Sus scrofa
Blostein, R.; Zhang, R.; Gottardi, C.J.; Caplan, M.J.
Functional properties of an H,K-ATPase/Na,K-ATPase chimera
J. Biol. Chem.
268
10654-10558
1993
Sus scrofa
De Pont, J.J.H.H.M.; Bonting, S.L.
Anion-sensitive ATPase and (K++H+)-ATPase
New Compr. Biochem.
2
209-234
1981
Frog, Oryctolagus cuniculus, Sus scrofa
-
Skrabanja, A.T.P.; van der Hijden, H.T.W.M.; de Pont, J.J.H.H.M.
Transport ratios of reconstituted (H++K+)-ATPase
Biochim. Biophys. Acta
903
434-440
1987
Sus scrofa
Lorentzon, P.; Jackson, R.; Wallmark, B.; Sachs, G.
Inhibition of (H++K+)-ATPase by omeprazole in isolated gastric vesicles requires proton transport
Biochim. Biophys. Acta
897
41-51
1987
Sus scrofa
Soumarmon, A.; Rangachari, P.K.; Lewin, M.J.M.
Passive transport of Rb+ by hog gastric (H+,K+)-ATPase
J. Biol. Chem.
259
11861-11867
1984
Sus scrofa
Faller, L.D.; Rabon, E.; Sachs, G.
Vanadate binding to the gastric H,K-ATPase and inhibition of the enzyme's catalytic and transport activities
Biochemistry
22
4676-4685
1983
Sus scrofa
Ivanov, D.; Dubreuil, N.; Raussens, V.; Ruysschaert, J.M.; Goormaghtigh, E.
Evaluation of the ordering of membranes in multilayer stacks built on an ATR-FTIR germanium crystal with atomic force microscopy: The case of the H+,K+-ATPase-containing gastric tubulovesicle membranes
Biophys. J.
87
1307-1315
2004
Sus scrofa
Diller, A.; Vagin, O.; Sachs, G.; Apell, H.J.
Electrogenic partial reactions of the gastric H,K-ATPase
Biophys. J.
88
3348-3359
2005
Sus scrofa
Abe, K.; Kaya, S.; Taniguchi, K.; Hayashi, Y.; Imagawa, T.; Kikumoto, M.; Oiwa, K.; Sakaguchi, K.
Evidence for a relationship between activity and the tetraprotomeric assembly of solubilized pig gastric H/K-ATPase
J. Biochem.
138
293-301
2005
Sus scrofa
Reenstra, W.W.; Crothers, J.; Forte, J.G.
The conformation of H,K-ATPase determines the nucleoside triphosphate (NTP) selectivity for active proton transport
Biochemistry
46
10145-10152
2007
Sus scrofa
Zimmermann, P.J.; Brehm, C.; Buhr, W.; Palmer, A.M.; Volz, J.; Simon, W.A.
Novel imidazo[1,2-a]pyrazine derivatives as potent reversible inhibitors of the gastric H+/K+-ATPase
Bioorg. Med. Chem.
16
536-541
2008
Sus scrofa
Zimmermann, P.J.; Buhr, W.; Brehm, C.; Palmer, A.M.; Feth, M.P.; Senn-Bilfinger, J.; Simon, W.A.
Novel indanyl-substituted imidazo[1,2-a]pyridines as potent reversible inhibitors of the gastric H+/K+-ATPase
Bioorg. Med. Chem. Lett.
17
5374-5378
2007
Sus scrofa
Fujii, T.; Ohira, Y.; Itomi, Y.; Takahashi, Y.; Asano, S.; Morii, M.; Takeguchi, N.; Sakai, H.
Inhibition of P-type ATPases by [(dihydroindenyl)oxy]acetic acid (DIOA), a K+ -Cl- cotransporter inhibitor
Eur. J. Pharmacol.
560
123-126
2007
Sus scrofa
Morii, M.; Yamauchi, M.; Ichikawa, T.; Fujii, T.; Takahashi, Y.; Asano, S.; Takeguchi, N.; Sakai, H.
Involvement of the H3O+-Lys-164-Gln-161-Glu-345 charge transfer pathway in proton transport of gastric H+,K+-ATPase
J. Biol. Chem.
283
16876-16884
2008
Sus scrofa
Nishizawa, T.; Abe, K.; Tani, K.; Fujiyoshi, Y.
Structural analysis of 2D crystals of gastric H+,K+-ATPase in different states of the transport cycle
J. Struct. Biol.
162
219-228
2008
Sus scrofa
Shin, J.M.; Munson, K.; Vagin, O.; Sachs, G.
The gastric HK-ATPase: structure, function, and inhibition
Pflugers Arch.
457
609-622
2009
Canis lupus familiaris, Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus, Sus scrofa
Witzke, A.; Lindner, K.; Munson, K.; Apell, H.J.
Inhibition of the gastric H,K-ATPase by clotrimazole
Biochemistry
49
4524-4532
2010
Sus scrofa
Garton, N.; Bailey, N.; Bamford, M.; Demont, E.; Farre-Gutierrez, I.; Hutley, G.; Bravi, G.; Pickering, P.
Discovery of biaryl inhibitors of H+/K+ ATPase
Bioorg. Med. Chem. Lett.
20
1049-1054
2010
Sus scrofa
Abe, K.; Tani, K.; Fujiyoshi, Y.
Structural and functional characterization of H+, K+-ATPase with bound fluorinated phosphate analogs
J. Struct. Biol.
170
60-68
2010
Sus scrofa (P19156)
Dach, I.; Olesen, C.; Signor, L.; Nissen, P.; le Maire, M.; M?ller, J.V.; Ebel, C.
Active detergent-solubilized H+,K+-ATPase is a monomer
J. Biol. Chem.
287
41963-41978
2012
Sus scrofa
Abe, K.; Tani, K.; Fujiyoshi, Y.
Systematic comparison of molecular conformations of H+,K+-ATPase reveals an important contribution of the A-M2 linker for the luminal gating
J. Biol. Chem.
289
30590-30601
2014
Sus scrofa
Abe, K.; Tani, K.; Friedrich, T.; Fujiyoshi, Y.
Cryo-EM structure of gastric H+,K+-ATPase with a single occupied cation-binding site
Proc. Natl. Acad. Sci. USA
109
18401-18406
2012
Sus scrofa
Xian, Y.; Zhao, X.; Wang, C.; Kang, C.; Ding, L.; Zhu, W.; Hang, S.
Phenylalanine and tryptophan stimulate gastrin and somatostatin secretion and H+-K+-ATPase activity in pigs through calcium-sensing receptor
Gen. Comp. Endocrinol.
267
1-8
2018
Sus scrofa
Jana, K.; Bandyopadhyay, T.; Ganguly, B.
Designed inhibitors with hetero linkers for gastric proton pump H+,K+-ATPase Steered molecular dynamics and metadynamics studies
J. Mol. Graph. Model.
78
129-138
2017
Sus scrofa (P19156 and P18434)
Paresi, C.J.; Liu, Q.; Li, Y.M.
Benzimidazole covalent probes and the gastric H+/K+-ATPase as a model system for protein labeling in a copper-free setting
Mol. Biosyst.
12
1772-1780
2016
Sus scrofa (P19156)
Abe, K.; Shimokawa, J.; Naito, M.; Munson, K.; Vagin, O.; Sachs, G.; Suzuki, H.; Tani, K.; Fujiyoshi, Y.
The cryo-EM structure of gastric H+,K+-ATPase with bound BYK99, a high-affinity member of K+-competitive, imidazo[1,2-a]pyridine inhibitors
Sci. Rep.
7
6632
2017
Sus scrofa (P19156 and P18434)
EXTERNAL LINKS (specific for EC-Number 7.2.2.19)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
