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Information on EC 7.2.2.19 - H+/K+-exchanging ATPase and Organism(s) Rattus norvegicus and UniProt Accession P09626
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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.
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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: Rattus norvegicus
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+-adenosinetriphosphatase
-
-
-
-
H+-K+-ATPase
H,K-ATPase
Proton pump
-
-
-
-
additional information
H+-K+-ATPase
-
-
-
-
H,K-ATPase
-
-
-
-
additional information
-
the enzyme is a member of the P2-type ATPase family
additional information
-
the enzymes belong to the X+,K+-ATPase superfamily
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
-
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+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
-
-
ir
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
cation binding sites in the transmembrane domains TM42 to TM6, E2-conformation-specific salt bridge between the side chains of Lys791 in TM5 and Glu820 in TM6 of the cation binding pocket
-
-
ir
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 enzyme could contribute to potassium and pH i regulation in cardiomyocytes
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the enzyme participates in K+ absorption and H+ secretion in the renal medulla, it is highly regulated in response to acid-base and electrolyte disturbances, colonic HKalpha2 plays a role in K+ and acid-base homeostasis as well as in early growth and development, it is also involved in maintainance of chronic metabolic alkalosis due to upregulation in hypokalemia, regulation of colonic HKalpha2 transcription and expression, overview
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the H,K-ATPase is the final step of acid secretion
-
-
?
additional information
?
-
activity tests of the recombinantly expressed enzyme by Rb+ uptake measurements, and voltage clamp fluorometry for site-specific labeling of H,KATPase-expressing TMRM-labeled oocytes
-
-
?
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
-
-
?
additional information
?
-
-
the enzyme is involved in acid secretion from gastric mucosa, overview
-
-
?
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
-
-
-
ir
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 enzyme could contribute to potassium and pH i regulation in cardiomyocytes
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the enzyme participates in K+ absorption and H+ secretion in the renal medulla, it is highly regulated in response to acid-base and electrolyte disturbances, colonic HKalpha2 plays a role in K+ and acid-base homeostasis as well as in early growth and development, it is also involved in maintainance of chronic metabolic alkalosis due to upregulation in hypokalemia, regulation of colonic HKalpha2 transcription and expression, overview
-
-
?
ATP + H2O + H+/in + K+/out
ADP + phosphate + H+/out + K+/in
-
the H,K-ATPase is the final step of acid secretion
-
-
?
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
-
-
?
additional information
?
-
-
the enzyme is involved in acid secretion from gastric mucosa, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Rb+
Rb+
-
uptake supported by both H+,K+-ATPase alpha subunit-Na+,K+-ATPase beta1 subunit complex or beta3 subunit complex, respectively, higher uptake in cells with H+,K+-ATPase alpha subunit-Na+,K+-ATPase beta1 subunit complex
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile
-
i.e. SCH28080
Ba2+
-
is a known inhibitor of K+ channels, and completely inhibits the whole-cell currents
digoxigenin
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
digoxin
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
dihydro-ouabain
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
ouabagenin
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
oubain
-
binding affinity of wild-type is 2000fold lower than that of mutated enzyme in NH4+-stimulated Sf9 cells
strophanthidin
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
trimethyltin chloride
-
i.e. TMT, trimethyltin chloride directly inhibits the activity of H+/K+-ATPases in renal intercalated cells reducing urine K+ reabsorption and inducing hypokalemia. It increases potassium leakage from the kidney, raises urine pH, and inhibits H+/K+-ATPase activity both in vitro and in vivo. In toxicated rats, H+/K+-ATPase activity is positively correlated with the decrease of plasma K+ and blood pH but is negatively correlated with the increase of urine K+ and urine pH, while trimethyltin chloride does not change the expression of H+/K+-ATPase protein and mRNA
SCH28080
low concentrations decrease phosphorylation levels of mutants with an E2 preference, whereas it hardly changes with E1-prefering mutants, even increases phosphorylation levels in the E820Q mutant
SCH28080
a K+-competitive inhibitor, SCH28080 is specific for both E2 and E2P conformations
Omeprazole
-
binding at Cys813 and Cys892 is reversible both in vivo and in vitro
Ouabain
-
inhibition of mutant D312E/S319G/A778P/I795L/F802C, not of the wild-type enzyme
additional information
-
chlorofom extract of Baccharis illinita flowers inhibits the H+-K+-ATPase and gastric acid secretion in rat stomach
-
additional information
-
wild-type non-gastric H,K-ATPase shows a very low affinity for ouabain
-
additional information
-
addition of trimethyltin chloride alters the whole-cell current and opens K+ channels in renal cells, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NH4+
-
stimulates ATPase activity of non-gastric H,K-ATPase-EGPLC by 40% as compared to wild-type
additional information
-
upregulation of HKalpha2 protein is a robust phenomenon, induced by multiple means of decreasing extracellular pH. Critical role for PKA in the maturation and function of the H+-K+-ATPase alpha-subunit and H+-ATPase, a mechanism that involves phosphorylation at key serine residues
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics, wild-type and mutant enzymes, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00017
strophanthidin
Rattus norvegicus
-
pH 7.0, 37°C, mutant D312E/S319G/A778P/I795L/F802C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
additional information
additional information
-
colonic HKalpha2 splicing variant colonic HKalpha2C is upregulated in newborn rats and undetectable in adult rats
additional information
-
chronic acidosis does not alter the expression of HKalpha2 mRNA, but PKA activity and HKalpha2 protein abundance increase when media pH decreases from pH 7.4 to pH 6.8
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
mutated H+,K+-ATPase alpha/beta1 subunit complex
-
microvilli of the expanded secretory canaliculus in the stimulated state of the parietal cell
-
coinciding of the nongastric H-K-ATPase alpha subunit with the beta1 subunit of Na-K-ATPase
-
membrane localization and topology model of HKalpha2, overview
-
apical membrane, cytoplasmic tubular membranes in the resting state
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the ubiquitous Na,K-ATPase and the gastric H,K-ATPase belong to the PIIC subgroup of the extensive class of P-type ATPases, which use ATP hydrolysis for active transport of cations. A lysine residue within the highly conserved center of the fifth transmembrane segment in PIIC-type ATPase alpha-subunits is uniquely found in H,K-ATPases instead of a serine in all Na,K-ATPase, EC 3.6.3.9, isoforms
physiological function
-
the H+-K+-ATPase alpha-subunit, HKalpha2, participates importantly in systemic acid-base homeostasis and defends against metabolic acidosis, showing pH-dependent regulation, overview. Regulatory role of pH-activated G protein-coupled receptor GPR4 in homeostatic regulation of HKalpha2 and acid-base balance
additional information
-
direct H+/K+-ATPase inhibition by trimethyltin chloride in renal intercalated cells reduces urine K+ reabsorption and induces hypokalemia, overview
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_RAT
1033
8
114038
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
alphabeta composition of HKalpha1 and HKalpha2, 1 * 35000, beta-subunit of HKalpha1
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
alphabeta composition of HKalpha1 and HKalpha2, 1 * 35000, beta-subunit of HKalpha1
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 model of the gastric H,K-ATPase in the E2 state
additional information
-
beta1-Na+,K+-ATPase is the physiologic beta-subunit of colonic HKalpha2
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
additional information
-
the beta-subunit of H,K-ATPase has an important function in maturation and plasma membrane targeting of the catalytic alpha-subunit but also modulate the transport activity of the holoenzymes
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
reversible phosphorylation of a highly conserved Asp residue, a hallmark of all P-type ATPases, is coupled to the transition between two principal conformational states and the corresponding phosphointermediates
glycoprotein
phosphoprotein
-
critical role for PKA in the maturation and function of the H+-K+-ATPase alpha-subunit and H+-ATPase, a mechanism that involves phosphorylation at key serine residues
glycoprotein
-
seven potential N-linked glycosylation sites are located in the putative extracellular regions of the protein
glycoprotein
-
N-linked glycosylation of beta-subunit, the absence of the huge N-linked oligosaccharide moiety on the beta-subunit in the glycosylation-deficient Asn-to-Gln beta-mutants does not affect alpha/beta co-assembly, plasma membrane delivery or functional activity of the holoenzyme, differences in neither the voltage-dependent E1P/E2P ratio nor the kinetics of the E1P/E2P transition between holoenzymes comprising glycosylated and glycosylation-deficient beta-subunits, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E820A
site-directed mutagenesis, shows altered pH dependence compared to the wild-type enzyme
E820D
site-directed mutagenesis, charge-conserving mutation, slight preference of the mutants for the E2P state, shows no altered pH dependence compared to the wild-type enzyme
E820K
site-directed mutagenesis, charge-inverting mutation, no shift in the conformational distribution toward E1P
E820Q
K791A
K791E
site-directed mutagenesis, charge-inverting mutation, insertion of the Lys791 mutations into the backbone of H,KATPase mutant S806C, which carries a reporter cysteine for site-specific fluorescence labeling. The mutation causes a conformational shift toward the E1P-state and a shift to more positive potentials compared with the wild-type
K791R
K791R/E343D
no K+-independent ATPase activity, no K+-stimulated dephosphorylation activity
K791R/E820Q
some K+-independent ATPase activity, no K+-stimulated dephosphorylation activity
K791S
S806C
a single cysteine replacement in the TM5/TM6 extracellular loop of the alpha-subunit. The S806C mutation enables site-specific labeling of H,K-ATPase with the environmentally sensitive fluorophore TMRM, the S806C mutation does not affect the transport properties of gastric H,K-ATPase
A778P/C781T
-
expression level rather similar to that of the recombinant enzyme, ability of binding 3(H)ouabain with high affinity
A778P/C781T/Y786F/V788I/G790N/L791I/I795L/I798V/F802C
-
expression level and 3(H)ouabain binding level rather similar to that of the recombinant enzyme
D312E/S319G/A778P/I795L/F802C
-
a ouabain-sensitive mutant of the non-gastric H,K-ATPase, with the mutant enzyme, strophanthidin and dihydroouabain have a higher and digoxin has a lower affinity than ouabain
I795L/I798V/F802C
-
expression level rather similar to that of the recombinant enzyme, ability of binding 3(H)ouabain with high affinity
K791S
-
the mutation greatly reduces enzyme activity as well as increases the Ki for 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile
N103Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N130Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N146Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N161Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N193Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N225Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
N99Q
-
site-directed mutagenesis, the mutation of the glycosylation site does not alter the enzyme's properties compared to the wild-type enzyme
S806C
Y309T/V310W/D312E/I314V/S319G
-
expression level rather similar to that of the recombinant enzyme, ability of binding 3(H)ouabain with high affinity
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
-
expression level rather similar, but 3(H)ouabain binding level significantly higher than that of the recombinant enzyme
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/C802F
-
3(H)ouabain binding level significantly lower than that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/E312D
-
3(H)ouabain binding level significantly lower than that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/G319S
-
3(H)ouabain binding level significantly lower than that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/L795I
-
3(H)ouabain binding level significantly lower than that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/P778A
-
3(H)ouabain binding level significantly lower than that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/T309Y
-
3(H)ouabain binding level not significantly different from that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/T781C
-
3(H)ouabain binding level not significantly different from that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/V314I
-
3(H)ouabain binding level not significantly different from that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/V798I
-
3(H)ouabain binding level not significantly different from that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C/W310V
-
3(H)ouabain binding level significantly higher that of mutant Y309T/V310W/D312E/I314V/S319G/A778P/C781T/I795L/I798V/F802C
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/Y786F/V788I/G790N/L791I
-
expression level and 3(H)ouabain binding level rather similar to that of the recombinant enzyme
Y309T/V310W/D312E/I314V/S319G/A778P/C781T/Y786F/V788I/G790N/L791I/I795L/I798V/F802C
-
expression level rather similar, but 3(H)ouabain binding level significantly higher than that of the recombinant enzyme
Y309T/V310W/D312E/I314V/S319G/Y786F/V788I/G790N/L791I/I795L/I798V/F802C
-
expression level and 3(H)ouabain binding level rather similar to that of the recombinant enzyme
Y44W/Y48W
-
beta-subunit mutation, tryptophan replacement of two highly conserved tyrosines in the transmembrane domain of gastric H,K-ATPase beta-subunits results in considerable shifts of the voltage-dependent E1P/E2P distributions toward the E1P state. Reverse binding of extracellular protons and subsequent E2P-E1P conversion is accelerated by the H,K-ATPase beta-Y44W/Y48Wmutation, and H+ secretion is strongly impaired
Y786F/V788I/G790N/L791I
-
expression level rather similar to that of the recombinant enzyme
additional information
E820Q
K+-insensitive activity and an E1 preference, E2 form-specific salt bridge between Glu820 and Lys791 is no longer possible
E820Q
site-directed mutagenesis, shows altered pH dependence compared to the wild-type enzyme
K791A
K+ affinity is markedly reduced without altering the E2 preference of the enzyme
K791A
site-directed mutagenesis, charge-neutralizing amino acid replacement, insertion of the Lys791 mutations into the backbone of H,KATPase mutant S806C, which carries a reporter cysteine for site-specific fluorescence labeling. The mutation causes a conformational shift toward the E1P-state and a shift to more positive potentials compared with the wild-type
K791R
site-directed mutagenesis, charge-inverting mutation, insertion of the Lys791 mutations into the backbone of H,KATPase mutant S806C, which carries a reporter cysteine for site-specific fluorescence labeling. The mutation causes a conformational shift toward the E1P-state and a shift to more positive potentials compared with the wild-type
K791S
site-directed mutagenesis, charge-neutralizing amino acid replacement, insertion of the Lys791 mutations into the backbone of H,KATPase mutant S806C, which carries a reporter cysteine for site-specific fluorescence labeling. The mutation causes a conformational shift toward the E1P-state and a shift to more positive potentials compared with the wild-type
S806C
-
alpha-subunit mutation, exchange in the extracellulae M5/M6 loop, the S806C mutation does not affect the transport properties of H,K-ATPase
additional information
inversion of the salt bridge polarity does not rescue function does not necessarily exclude that Lys791 and Glu820 in the wild-type proton pump interact in an E2P-stabilizing manner
additional information
-
mutation of 84 amino acids in the carboxy-terminus, incapable of sustaining functionality
additional information
-
the absence of the huge N-linked oligosaccharide moiety on the beta-subunit in the glycosylation-deficient Asn-to-Gln beta-mutants does not affect alpha/beta co-assembly, plasma membrane delivery or functional activity of the holoenzyme, differences in neither the voltage-dependent E1P/E2P ratio nor the kinetics of the E1P/E2P transition between holoenzymes comprising glycosylated and glycosylation-deficient beta-subunits, overview
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes partially from Xenopus laevis oocytes by plasma membrane preparation
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the beta-subunit and a modified form of the alpha-subunit with a single cysteine replacement in the TM5/TM6 extracellular loop, i.e. S806C, in Xenopus laevis oocytes
catalytic subunit of the enzyme, in which several amino acids from Na,K-ATPase are incorporated, expressed with the Na,K-ATPase beta1 subunit in Xenopus laevis oocytes, expression of non-gastric H,K-ATPase-EGPLC and the Na,K-ATPase beta1-subunit in Sf9 cells using the baculovirus expression system
-
expression of alpha-subunit of wild-type and mutant enzymes in Spodopera frugiperda Sf9 cell membranes using the baculovirus transfection system
-
expression of the wild-type H,K-ATPase, alpha- and beta-subunits, and glycosylation-deficient Asn-to-Gln beta-mutants in Xenopus laevis oocytes
-
functional expression of the HKalpha2 subunit in human HEK-293 cells, human GPR4 is transiently transfected into HEK-293 cells stably expressing HKalpha2/NKbeta1, expression levels under different conditions by realtime PCR expression analysis
-
into pcDNA3.1(+)-Neo, cotransfection of HEK-293 cells with H+,K+-ATPase alpha subunit plus Na+,K+-ATPase beta1 subunit or beta3 subunit, respectively
-
into pcDNA3.1(+)-Neo, expression in HEK-293 cells, mutant cloned into pEGFP-2C vector
-
transfection of Saccharomyces cerevisiae AH109 with pGBKT7 containing an insert encoding the 84 carboxy-terminal acids of HKalpha2, cotransfection of HEK-293 cells with HKalpha2 plus NKbeta1
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
chronic acidosis and G protein-coupled receptor GPR4 increase HKalpha2 protein by increasing protein kinase A activity without altering HKalpha2 mRNA abundance. Heterologous expression of GPR4 is sufficient to increase both basal and acid-stimulated HKalpha2 expression. Upregulation of HKalpha2 by chronic acidosis is reversible
-
trimethyltin chloride does not change the expression of H+/K+-ATPase protein and mRNA
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the salt bridge between Glu820 and Lys791 is essential for high-affinity K+ binding and the E2 preference of the enzyme
additional information
-
beta1 subunit is the predominant isoform in nongastric H-K-ATPase
additional information
-
carboxy-terminus of the H+,K+-ATPase alpha subunit facilitates the proper folding of the H+,K+-ATPase alpha/beta1 subunit complex allowing translocation to the plasma membrane where K+ uptake occurs, otherwise the complex is destined for degradation
additional information
-
CD63 functions as a negative regulator of the colonic H+-K+-ATPase, specifically interacts with carboxy terminus of the enzyme, supression of CD63 protein synthesis in HEK-293 cells increases Rb+ uptake by the HKalpha2/NKbeta1 complex
additional information
-
Na+,K+-ATPase is likely to represent the most physiologic and efficient subunit for H+,K+-ATPase alpha subunit assembly in distal colon
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Rattus norvegicus
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Rattus norvegicus
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68
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Rattus norvegicus
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286
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Rattus norvegicus
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CD63 interacts with the carboxy terminus of the colonic H+-K+-ATPase to increase plasma membrane localization and 86Rb+ uptake
Am. J. Physiol.
288
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Mus musculus, Rattus norvegicus
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A conformation-specific interhelical salt bridge in the K+ binding site of gastric H,K-ATPase
J. Biol. Chem.
279
16417-16424
2004
Rattus norvegicus (P09626)
Qiu Li, Y.; Swarts Herman, G.P.; Tonk Elisa, C.M.; Willems Peter, H.G.M.; Koenderink Jan, B.; De Pont Jan Joep, H.H.M.
Conversion of the low affinity ouabain-binding site of non-gastric H,K-ATPase into a high affinity binding site by substitution of only five amino acids
J. Biol. Chem.
281
13533-13539
2006
Rattus norvegicus
Li, J.; Codina, J.; Petroske, E.; Werle, M.J.; DuBose, T.D.
The carboxy terminus of the colonic H+,K+-ATPase alpha-subunit is required for stable beta subunit assembly and function
Kidney Int.
65
1301-1310
2004
Rattus norvegicus
Li, J.; Codina, J.; Petroske, E.; Werle, M.J.; Willingham, M.C.; DuBose, T.D.
The effect of beta-subunit assembly on function and localization of the colonic H+,K+-ATPase alpha-subunit
Kidney Int.
66
1068-1075
2004
Rattus norvegicus
Duerr, K.L.; Tavraz, N.N.; Zimmermann, D.; Bamberg, E.; Friedrich, T.
Characterization of Na,K-ATPase and H,K-ATPase enzymes with glycosylation-deficient beta-subunit variants by voltage-clamp fluorometry in Xenopus oocytes
Biochemistry
47
4288-4297
2008
Rattus norvegicus
Codina, J.; DuBose, T.D.
Molecular regulation and physiology of the H+,K+-ATPases in kidney
Semin. Nephrol.
26
345-351
2006
Mus musculus, Rattus norvegicus
Duerr, K.L.; Tavraz, N.N.; Dempski, R.E.; Bamberg, E.; Friedrich, T.
Functional significance of E2 state stabilization by specific alpha/beta-subunit interactions of Na,K- and H,K-ATPase
J. Biol. Chem.
284
3842-3854
2009
Rattus norvegicus
Freitas, C.S.; Baggio, C.H.; Finau, J.; Anginoni, M.; Pizzolatti, M.G.; Santos, A.R.; Marques, M.C.
Inhibition of H+/K+ ATPase in the gastroprotective effect of Baccharis illinita DC
J. Pharm. Pharmacol.
60
1105-1110
2008
Oryctolagus cuniculus, Rattus norvegicus
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
De Pont, J.J.; Swarts, H.G.; Karawajczyk, A.; Schaftenaar, G.; Willems, P.H.; Koenderink, J.B.
The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase
Pflugers Arch.
457
623-634
2009
Rattus norvegicus
Tang, X.; Yang, X.; Lai, G.; Guo, J.; Xia, L.; Wu, B.; Xie, Y.; Huang, M.; Chen, J.; Ruan, X.; Sui, G.; Ge, Y.; Zuo, W.; Zhao, N.; Zhu, G.; Zhang, J.; Li, L.; Zhou, W.
Mechanism underlying hypokalemia induced by trimethyltin chloride: Inhibition of H+/K+-ATPase in renal intercalated cells
Toxicology
271
45-50
2010
Rattus norvegicus
Codina, J.; Opyd, T.S.; Powell, Z.B.; Furdui, C.M.; Petrovic, S.; Penn, R.B.; DuBose, T.D.
pH-dependent regulation of the alpha-subunit of H+-K+-ATPase (HKalpha2)
Am. J. Physiol. Renal Physiol.
301
F536-F543
2011
Rattus norvegicus
Duerr, K.L.; Seuffert, I.; Friedrich, T.
Deceleration of the E1P-E2P transition and ion transport by mutation of potentially salt bridge-forming residues Lys-791 and Glu-820 in gastric H+/K+-ATPase
J. Biol. Chem.
285
39366-39379
2010
Rattus norvegicus (P09626)
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