Information on EC 3.6.3.9 - Na+/K+-exchanging ATPase

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY
3.6.3.9
-
RECOMMENDED NAME
GeneOntology No.
Na+/K+-exchanging ATPase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Na+/in + K+/out = ADP + phosphate + Na+/out + K+/in
show the reaction diagram
formation of a phosphorylated intermediate
-
ATP + H2O + Na+/in + K+/out = ADP + phosphate + Na+/out + K+/in
show the reaction diagram
reaction sequence and transport mechanism
-
ATP + H2O + Na+/in + K+/out = ADP + phosphate + Na+/out + K+/in
show the reaction diagram
the enzyme gamma subunit is located adjacent to the M2-M6-M9 pocket of the alpha subunit at the transmembrane-extracellular interface. During the E1 to E2 transition, there is no relative change in distance between the alpha and gamma subunits but there is a relative change in distance between the beta and gamma subunits
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphate bond
-
-
-
-
hydrolysis of phosphonic ester bond
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
hydrolysis of phosphoric ester
-
-
transmembrane transport
-
-
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
transmembrane transport
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (Na+/K+-exchanging)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This is a plasma membrane enzyme, ubiquitous in animal cells, that catalyses the efflux of three Na+ and influx of two K+ per ATP hydrolysed. It is involved in generating the plasma membrane electrical potential.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(Na+ + K+)-activated ATPase
-
-
-
-
(Na+ + K+)-ATPase
-
-
-
-
(Na+, K+)-ATPase
-
-
(Na+, K+)-dependent ATPase
-
-
(Na+,K+)-activated ATPase
-
-
-
-
(Na+-K+)-ATPase
-
-
-
-
E.C.3.6.1.37
-
formerly
EC 3.6.1.3
-
-
related
-
EC 3.6.1.37
-
-
formerly
-
Na(+)-K(+)-exchanging ATPase
-
-
Na+ pump
-
-
Na+, K+-ATPase
-
-
Na+, K+-ATPase
-
-
Na+,K+ pump
-
alpha1-, alpha2-, beta1-, beta2-subunits
Na+,K+-adenosine triphosphatase
-
-
Na+,K+-ATPase
-
-
-
-
Na+,K+-ATPase
-
-
Na+,K+-ATPase
-
-
Na+,K+-ATPase
-
-
Na+,K+-ATPase
-
-
Na+,K+-ATPase
-
-
Na+,K+-ATPase
Q4H132
-
Na+,K+-ATPase
-
-
Na+,K+-pump
-
-
Na+,K+-pump
-
-
Na+-K+ ATPase
-
-
Na+-K+ ATPase
-
-
Na+-K+ ATPase
-
-
Na+-K+ pump
-
-
Na+-K+ pump alpha1-isoform
-
-
Na+-K+ pump alpha2-isoform
-
-
Na+-K+-ATPase
-
alpha1-beta1 isoenzyme; alpha2-beta1 isoenzyme
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
-
Na+-K+-ATPase
-
; alpha1-, beta1-subunits
Na+-K+-ATPase
-
-
Na+-K+-ATPase alpha2-isoform
-
in comparison to a cardiac glycoside resistant alpha2-isoform
Na+-K+-pump
-
-
Na+/K+ -ATPase
-
-
Na+/K+ ATPase
-
-
-
-
Na+/K+ ATPase
-
-
Na+/K+ pump
-
-
Na+/K+-ATPase
-
-
Na+/K+-ATPase
-
-
Na+/K+-ATPase
-
-
Na+/K+-ATPase
-
-
Na+/K+-ATPase
-
-
Na+K+ATPase
-
-
Na, K-ATPase
-
-
Na,K pump
-
-
Na,K-activated ATPase
-
-
-
-
Na,K-adenosine triphosphatase
-
-
Na,K-ATPase
-
-
-
-
Na,K-ATPase
-
-
Na,K-ATPase
-
-
Na,K-ATPase
-
-
Na,K-ATPase
-
-
Na,K-Pump
-
-
-
-
Na,K-Pump
-
-
Na-K-ATPase
-
-
Na/K pump
-
-
Na/K-ATPase
-
-
Na/K-ATPase
-
-
Na/K-ATPase
-
-
Na/K-ATPase
-
-
Na/K-ATPase
-
-
NKA
C0KXH0
-
NKA
-
-
renal sodium-potassium pump
-
-
sodium pump
-
-
-
-
sodium pump
-
-
sodium pump
-
-
sodium-potassium pump
Q4H132
-
sodium/potassium ATPase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
alpha-1 subunit
UniProt
Manually annotated by BRENDA team
dogfish
-
-
-
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
9 different isoenzymes
-
-
Manually annotated by BRENDA team
patients with familial rapid-onset dystonia parkinsonism
-
-
Manually annotated by BRENDA team
three Na,K-ATPase isozymes, alpha1beta1, alpha2beta1, and alpha3beta1
-
-
Manually annotated by BRENDA team
untrained volunteers
-
-
Manually annotated by BRENDA team
juvenile shrimp fed diet rich/low in highly unsaturated fatty acids
-
-
Manually annotated by BRENDA team
freshwater shrimp
-
-
Manually annotated by BRENDA team
alpha-subunit
UniProt
Manually annotated by BRENDA team
subunit alpha-1b
UniProt
Manually annotated by BRENDA team
New Zealand white rabbit
-
-
Manually annotated by BRENDA team
newborn lamb
-
-
Manually annotated by BRENDA team
Pareledone sp.
alpha-subunit
UniProt
Manually annotated by BRENDA team
alpha-subunit
UniProt
Manually annotated by BRENDA team
hyper- and hypothyroid adult rats
-
-
Manually annotated by BRENDA team
male adult Wistar rats
-
-
Manually annotated by BRENDA team
Spargue-Dawley rats
-
-
Manually annotated by BRENDA team
Sprague Dawley rat
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Wistar rat
-
-
Manually annotated by BRENDA team
Wistar rats
-
-
Manually annotated by BRENDA team
Wistar-Kyoto rats
-
-
Manually annotated by BRENDA team
with induced neonatal hypothyroidism
-
-
Manually annotated by BRENDA team
acclimation from fresh water to seawater is accompanied by 8fold increase in enzyme activity and 3fold increase in enzyme protein number. Enzyme activity in seawater fish is negatively correlated with basolateral membrane cholesterol content and positively correlated with phosphatidylethanolamine and linoleic acid content. Activity in freshwater fish is not correlated to any membrane lipid parameter
-
-
Manually annotated by BRENDA team
alpha-subunit
Uniprot
Manually annotated by BRENDA team
commercial product
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
inactivation of Na+, K+-ATPase leads to partial membrane depolarization allowing excessive Ca2+ entry inside neurons with resultant toxic events such as excitotoxicity
physiological function
-
Na+, K+-ATPase plays a role in regulating electrolyte concentration in the lens, contributing to lens transparency, and is involved in cataract formation caused by prolonged use of glucocorticoids, that suppress the Na+,K+-ATPase in the lens, overview
physiological function
-
Na+, K+-ATPase plays an important role in pulmonary inflammation
physiological function
Q4H132
Na+,K+-ATPase is responsible for establishing Na+ and K+ concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials
physiological function
-
Na/K-ATPase is a plasma membrane protein complex transferring the stored energy of ATP to the active transport of Na+ and K+ ions across the cell membrane. Na/K-ATPase alpha1 isoform modulates signaling mechanisms leading to apoptosis, cell migration, and cell proliferation
physiological function
-
Na/K-ATPase is a plasma membrane protein complex transferring the stored energy of ATP to the active transport of Na+ and K+ ions across the cell membrane. The generated electrochemical gradient is essential for a number of other cellular functions
physiological function
-
Klotho is a transmembrane protein with particularly strong expression in kidney, parathyroid glands and choroid plexus. Expression of Klotho in Xenopus oocytes increases the Na+/K+ ATPase pump current. Treatment of Xenopus oocytes with Klotho protein similarly increases the pump current
physiological function
-
Klotho is a transmembrane protein with particularly strong expression in kidney, parathyroid glands and choroid plexus. Klotho-hypomorphic mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism. Na+/K+ ATPase protein abundance in isolated collecting ducts is lower in Klothohm mice than in their wild type littermates
physiological function
-
the degree of activation of Na+/K+-ATPase at physiological Na+-concentrations differs between oxidative and glycolytic muscles and between subcellular membrane domains with different isoform compositions
metabolism
-
in vivo administration of isovaleric acid inhibits the citric acid cycle probably through the enzyme citrate synthase, as well as Na+,K+-ATPase, a crucial enzyme responsible for maintaining the basal potential membrane necessary for a normal neurotransmission, inhibition of these activities may be involved in the pathophysiology of the neurological dysfunction of isovaleric academic patients. Isovaleric acidemia is an autosomal recessive inherited metabolic disorder of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase
additional information
-
crucial role for Na+/K+-ATPase activity in determining neuronal vulnerability to domoic acid-mediated excitotoxicity. The enzyme inhibitor palytoxin enhances vulnerability of cultured cerebellar neurons to domoic acid via sodium-dependent mechanisms, overview
additional information
-
ETB receptor inhibits Na+-K+ ATPase activity by facilitating extracellular Ca2+ entry and Ca2+ release from endoplasmic reticulum. The inhibitory effect is abolished by chelator of intracellular-free calcium BAPTA-AM, Ca2+ channel blocker nicardipine, inositol 1,4,5-trisphosphate receptor blocker 2-aminoethyl diphenyl borate, and PI3 kinase inhibitor wortmannin, overview
additional information
-
ethanol-induced Na+,K+-ATPase inhibition leads to cerebellar dysfunction causing motor coordination impairments and cognitive deficits, and may also contribute to neuronal function alterations in other brain regions, overview. Ethanol increases firing frequency and regularity of spontaneous firing in presence of neurotransmitter receptor antagonists, ethanol increases spontaneous firing frequency and depolarizes the membrane potential, overview
additional information
-
inhibition of proliferation of Panc-1 cells by oleandrin is significantly reduced when the relative expression of subunit alpha3 is decreased or when the expression of the alpha1 isoform is increased
additional information
-
Na+, K+-ATPase inhibition by cardiotonic steroids increases COX-2 expression in A-549 cells, overview
additional information
-
Na+,K+-ATPase alpha1 subunit is one of the targets for reactive oxygen species and is directly involved in oxidative stress. alpha1 Subunit level decrease after fluid percussion injury inducing traumatic brain injury in rats, overview. Physical training is effective against Na+,K+-ATPase enzyme activity inhibition, while fluid percussion injury induces a decrease in Na+,K+-ATPase activity in the ipsilateral cerebral cortex of sedentary animals
additional information
-
Na+,K+-ATPase inhibitor ouabain triggers an apoptotic cascade that involves NCX and CaMKII as a downstream effector. Ouabain simultaneously activates an antiapoptotic cascade involving PI3K/AKT which is however, insufficient to completely repress apoptosis. KN93 prevents ouabain-induced apoptosis without affecting inotropy
additional information
-
odoroside A and ouabain potently reduce NF-kappaB-inducible de novo protein synthesis, largely due to its ability to block Na+-dependent transport of amino acids across the plasma membrane, but not to interfering with the translation machinery
additional information
-
the Na/K-ATPase-derived, membrane-bound peptide inhibits the activity of Src kinase targeting the Na/K-ATPase/Src receptor complex and antagonizing ouabain-induced protein kinase cascades in rat cardiomyocytes, molecular mechanism of Na/KATPase-mediated Src regulation, overview. NaKtide does not directly affect the ERK and protein kinase C family of kinases. It inhibits Lyn with a much lower potency with IC50 of 0.0025 mM
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + phosphate + 3 Na+/out
ATP + 3 Na+/in
show the reaction diagram
-
in the absence of K+ and in the presence of ATP and ADP without net ATP hydrolysis
transphosphorylation of ATP/ADP
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
r
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
r
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
-
-
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
Pareledone sp.
F8V2T5
-
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
F8V2T6
-
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
-
enzyme has a high- and a low-affinity ATP hydrolizing site
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
-
reaction obeys Michaelis-Menten kinetics
-
-
?
ATP + 3 Na+/in
ADP + phosphate + 3 Na+/out
show the reaction diagram
F8V2T5
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O + 3 Na+/in + 2 K+/out
ADP + phosphate + 3 Na+/out + 2 K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
r
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in
ADP + phosphate + Na+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
Frog
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
shark
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
dogfish
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
Q4H132
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
a continous Na+ influx exists across the plasma membrane in the presence of external Na+. When Na+ is removed from both external and internal solutions, a transient outward pump current is observed by adding K+ to the external solution, thus indicating that the transient pump current is activated by the residual intracellular Na+
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
enzyme does not show a distinct voltage dependency either with or without extracellular Na+. In presence of extracellular Na+ a steady Na+-K+ pump current exists even in absence of internal Na+. A steady Na+-K+ pump current is observed with 10 mM intracellular Na+
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
for each ATP molecule hydrolyzed three Na+ ions are transported out of and two K+ ions into the cell
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
formation of a phosphorylated intermediate
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
may not play a significant role in adaption in freshwater crustaceans
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
enzyme plays a crucial role in cellular ion homeostasis
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
creation of a electrochemical gradient of Na+ ions into and K+ ions out of the cell
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
modelling of enzyme function in neurons in absence or presence of ethanol, overview
-
-
?
ATP + H2O + Na+/in + Rb+/out
ADP + phosphate + Na+/out + Rb+/in
show the reaction diagram
-
measurement of enzyme activity by ouabain-sensitive 86Rb+ uptake
-
-
?
ATP + H2O + Na+/in + Rb+/out
ADP + phosphate + Na+/out + Rb+/in
show the reaction diagram
-
measurement of enzyme activity by ouabain-sensitive Rb+ uptake
-
-
?
ATP + H2O + Na+in + K+out
ADP + phosphate + Na+out + K+in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+in + K+out
ADP + phosphate + Na+out + K+in
show the reaction diagram
-
-
-
-
?
ATP + Na+/in
ADP + phosphate + Na+/out
show the reaction diagram
-
-
-
-
?
ATP + Na+/in
ADP + phosphate + Na+/out
show the reaction diagram
-
under saturating Mg2+, Na+, and K+ conditions, enzyme exhibits two well-defined ATP hydrolyzing sites. At the high-affinity sites, K0.5 value is 63.8 nmol per l, at the low-affinity sites, hydrolysis follows Michaelis-Menten kinetics
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
beta-(2-furyl)acryloyl phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
K+-dependent ATPase activity in absence of Na+ at acid pH, protons can be transported by the sodium pump in place of Na+
-
-
-
additional information
?
-
-
the enzyme also catalyzes: 1. uncoupled Na+ efflux in presence of Na+/in, Mg2+ and ATP, 2. Na+-dependent ADP/ATP exchange, 3. K+-dependent enzyme phosphorylation by phosphate
-
-
-
additional information
?
-
-
electrogenic Na+K+-ATPase partially contributes to the ustained hyperpolarization of endothelial cells in response to acetylcholine
-
-
-
additional information
?
-
-
Na+K+-ATPase actively participates in the regulation of endosomal pH value and endocytosed membrane traffic
-
-
-
additional information
?
-
-
subunit isoform alpha2 abundance is higher in the t-tubules than in the surface sarcolemma. The isoform is functinally coupled to the Na+/Ca2+-exchanger and can regulate Ca2+ handling without changing global concentration of Na+
-
-
-
additional information
?
-
-
the Na/K-ATPase-derived, membrane-bound peptide inhibits the activity of Src kinase targeting the Na/K-ATPase/Src receptor. ND1 as a Src-interacting domain from the Na/K-ATPase alpha1 subunit, overview
-
-
-
additional information
?
-
-
assay using solid-supported membrane, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
-
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
r
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
-
each cycle extrudes 3 Na+ from the cell and moves 2 K+ into the cell with utilization of 1 ATP
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
r
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
Q4H132
-
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
may not play a significant role in adaption in freshwater crustaceans
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
enzyme plays a crucial role in cellular ion homeostasis
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
creation of a electrochemical gradient of Na+ ions into and K+ ions out of the cell
-
-
?
ATP + H2O + Na+/in + K+/out
ADP + phosphate + Na+/out + K+/in
show the reaction diagram
-
modelling of enzyme function in neurons in absence or presence of ethanol, overview
-
-
?
ATP + H2O + Na+in + K+out
ADP + phosphate + Na+out + K+in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Na+in + K+out
ADP + phosphate + Na+out + K+in
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
electrogenic Na+K+-ATPase partially contributes to the ustained hyperpolarization of endothelial cells in response to acetylcholine
-
-
-
additional information
?
-
-
Na+K+-ATPase actively participates in the regulation of endosomal pH value and endocytosed membrane traffic
-
-
-
additional information
?
-
-
subunit isoform alpha2 abundance is higher in the t-tubules than in the surface sarcolemma. The isoform is functinally coupled to the Na+/Ca2+-exchanger and can regulate Ca2+ handling without changing global concentration of Na+
-
-
-
additional information
?
-
-
the Na/K-ATPase-derived, membrane-bound peptide inhibits the activity of Src kinase targeting the Na/K-ATPase/Src receptor. ND1 as a Src-interacting domain from the Na/K-ATPase alpha1 subunit, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
-
activates
Ca2+
-
activates
Cr3+
-
causes oxidative stress in fish and leads to reduced enzyme activity in the brain, mechanism, overview. The level of ATP production in brain mitochondria may be an important criteria in the CrIII induced inhibition of Na+K+ATPase activity of fish brain, reduction of Na+K+ATPase activity is partially mediated by lipid peroxidation and deficient mitochondrial electron transport chain activity. Also direct interaction of CrIII ion with the -SH group of Na+K+ATPase enzyme might play a role
Cs+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. K+ can be replaced by the following monovalent cations in the order of decreasing activation: K+, Rb+, NH4+, Cs+, Li, Na+
K+
-
half-activated by 2.0 mM
K+
-
completely abolishes oubain binding to alpha1-beta1 isoenzymes. Residual oubain binding is still observed at high K+ concentrations for alpha2-beta1 and alpha3-beta1 complexes
K+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. K+ can be replaced by the following monovalent cations in the order of decreasing activation: Rb+, NH4+, Cs+, Li, Na+
K+
-
activation mechanism in simultaneous presence of Na+ and K+
K+
-
stimulation, following a single saturation curve. Synergistic effects of K+ and NH4+. Km value 1.5 mM
K+
-
stimulation, following a single saturation curve. Synergistic effects of K+ and NH4+
K+
-
stimulation, synergistic effect of NH4+ and K+. Enzyme exhibits a single K+ binding site, NH4+ binding to a second, exlcusive site
K+
-
the KCl concentration giving the half-maximal activity i 1.2 mM. The Na+:K+ ratios giving the maximal activity are 1:3 to 3:1
Li+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. K+ can be replaced by the following monovalent cations in the order of decreasing activation: K+, Rb+, NH4+, Cs+, Li, Na+
Mg2+
-
required
Mg2+
-
-
Mg2+
-
maximal activity at 5 mM Mg2+
Mg2+
-
stimulation, following a single saturation curve. K0.5 value 0.36 mM
Mg2+
-
stimulation, following a single saturation curve
Mg2+
-
stimulation
Mg2+
-
required
Mg2+
-
required
Mg2+
Q4H132
required
Na+
-
half-activated by 9.6 mM
Na+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. Na+ cannot be replaced by any other monovalent cation. K+ can be replaced by the following monovalent cations in the order of decreasing activation: K+, Rb+, NH4+, Cs+, Li, Na+
Na+
-
activation mechanism in simultaneous presence of Na+ and K+
Na+
-
stimulation, following a single saturation curve. Km value 7.4 mM
Na+
-
stimulation, following a single saturation curve
Na+
-
stimulation
Na+
-
the NaCl concentration giving the halfmaximal activity is 6.0 mM. The Na+:K+ ratios giving the maximal activity are 1:3 to 3:1
NH4+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. K+ can be replaced by the following monovalent cations in the order of decreasing activation: K+, Rb+, NH4+, Cs+, Li, Na+
Rb+
-
the Na,K pump is activated by the combined effect of Na+ on the cytoplasmic side and of K+ on the extracellular side of the membrane. K+ can be replaced by the following monovalent cations in the order of decreasing activation: K+, Rb+, NH4+, Cs+, Li, Na+
Mg2+
-
the optimal concentration of MgCl2 is 3 mM in presence of 10 mM NaCl and 30 mM KCl
additional information
-
CaCl2 up to 300 microM does not affect Na+/K+-ATPase activity, but CaCl2 above 1 mM inhibits the activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-2,3a,11,11a-tetrahydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
-
(1R,2R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9-(hydroxymethyl)-15a-methyl-1-(5-oxo-2,5-dihydrofuran-3-yl)-2-(2-oxopropanoyl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
-
(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-13a-formyl-3a,11a-dihydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-11-yl beta-D-glucopyranoside
-
-
(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
-
(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9-(hydroxymethyl)-15a-methyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
-
1,8,9-trihydroxy-3-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
i.e. wedelolactone, inhibitor of kidney Na+K+-ATPase and ligand for the central benzodiazepine receptor
1-chloro-2,4-dinitrobenzene
-
inhibition of the transport activity of the Na-K pump
12,20-dihydroxydammar-24-en-3-yl 2-O-D-glucopyranosyl-D-glucopyranoside
-
-
12,20-dihydroxydammar-24-en-3-yl D-glucopyranoside
-
-
19-hydroxy-2''-oxovoruscharin
-
i.e. UNBS1450, a trans-trans-cis cardiotonic steroid
1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one
-
ODQ, inhibition of SNP-induced pump stimulation
2,3-dihydroxy-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-6-one
-
inhibitor of kidney Na+K+-ATPase and ligand for the central benzodiazepine receptor
2,8,9-trihydroxy-3-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
inhibitor of kidney Na+K+-ATPase and ligand for the central benzodiazepine receptor
2,9-dihydroxy-3,8-dimethoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
inhibitor of kidney Na+K+-ATPase and ligand for the central benzodiazepine receptor
2-aminoethyl-methanethiosulfonate
-
inhibition of mutants F323C, P333C, E334C, G335C, I322C, G326C and A330C
3,8,9-trihydroxy-2-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
inhibitor of kidney Na+K+-ATPase and ligand for the central benzodiazepine receptor
3-[(2-O-D-glucopyranosyl-D-glucopyranosyl)oxy]-12-hydroxydammar-24-en-20-yl D-glucopyranoside
-
-
4,7-diacetoxy-14-hydroxydolast-1(15),8-diene
-
-
4-acetoxy-9,14-dihydroxydolast-1(15),7-diene
-
-
4-[(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15R,15aS)-3a,11,11a,15-tetrahydroxy-13a-(hydroxymethyl)-9,15a-dimethylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
-
4-[(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9,13a-bis(hydroxymethyl)-15a-methylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
-
4-[(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15R,15aS)-3a,11,11a,15-tetrahydroxy-9,13a-bis(hydroxymethyl)-15a-methylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
-
5-hydroxydecanoate
-
presence of 5 mM ATP, inhibitory above 1 mM. Presence of 0.05 mM ATP, inhibitory above 0.25 mM. No effect on ouabain-sensitiviy of the enzyme
8-methoxycoumestrol
-
inhibits the isozyme alpha1beta1 Na,K-ATPase, mechanism, overview
A-769662
-
inhibits the Na+-K+-ATPase transport activity and cell surface abundance in L6 cells, which is independent of AMP kinase activation, overview
alpha2-adrenergic agonists
-
negative modulator
-
astragaloside III
-
from dried roots of Astragalus membraneceus or var. mongholicus
ATP
-
competitive inhibitor of K+-phosphatase activity
BAY-K8644
-
a calcium channel agonist, the effect is blocked by a phosphatidylinositol-3 kinase inhibitor wortmannin
benzyltriethylammonium chloride
-
inhibition of pump current is dependent on membrane potential
beta-acetyldigoxin
-
-
bradykinin
-
negative modulator
bufalin
-
inhibition of the enzyme, enhancement of the acidification of the late endosome, alteration in membrane traffic
bufalin
-
from dried venom of Bufo gargarizans or Bufo bufo melanostictus
Ca2+
-
enzyme from anterior intestine is 5-fold more sensitive than enzymes from pyloric caeca and posterior intestine
Ca2+
-
CaCl2 up to 300 microM does not affect Na+/K+-ATPase activity, but CaCl2 above 1 mM inhibits the activity
chlorpromazine
-
-
cholic acid
-
from dried bile of Ursus arctos or Selenarctos thibetanus
cyclosporin A
-
diminishs induction of alpha1 protein in activated lymphocytes
dammar-24-ene-3,12,20-triol
-
-
dammar-24-ene-3,6,12,20-tetrol
-
-
dansylcysteinyl-mercuric chloride
-
-
digitoxigenin
-
-
digitoxigenin
-
-
digitoxin
-
-
dihydroouabain
-
-
diphenyl diselenide
-
activity is restored by DTT
dopamine
-
negative modulator
endobain E
-
-
-
endothelin
-
negative modulator
-
epicatechin
-
-
epicatechin-3-gallate
-
solubilization of the Na+,K+-ATPase with a nonionic detergent reduces sensitivity to epigallocatechin-3-gallate
epigallocatechin
-
-
epigallocatechin-3-gallate
-
noncompetitive with respect to ATP, reduces the affinity for vanadate, shifts the equilibrium of E1P and E2P toward E1P, and reduces the rate of the E1P to E2P transition
Ethacrynic acid
-
-
Ethacrynic acid
-
-
ethanol
-
inhibits the enzyme in Golgi membranes of cerebellar neurons leading to potentiation of GABAergic transmission at Golgi cell-to-granule cell synapses throughan increase in Golgi cell excitability
ethylester of glutathione
-
inhibition of the transport activity of the Na-K pump
ethylmercurithiosalicylate
-
-
fenoldopam
-
induces inhibition of Na+ ?K+-ATPase activity in HK-2 cells. Ouabain protects against the cyclic adenosine monophosphate accumulation and Na+ ?K+-ATPase inhibition induced by the D1 receptor agonist fenoldopam in HK-2 cells. Chronic ouabain treatment decreases the protein and mRNA expression levels of the D1 receptor and increases the basal phosphorylation of the D1 receptor in HK-2 cells
foliandrin
-
-
genistein
-
tyrosine kinase inhibitor, block phosphorylation of alpha-subunit of the Na+,K+-ATPase
ginsenoside Rh2
-
from dried roots of Panax ginseng or Panax notoginseng
glibenclamide
-
-
glyburide
-
presence of 5 mM ATP, slightly stimulating up to 1 mM, inhibitory above. Presence of 0.05 mM ATP, stimulating at least up to 3 mM
glycyrrhizin
-
from roots of Glycyrrhiza uralensis , Glycyrrhiza inflata, or Glycyrrhiza glabra
herbimycin A
-
tyrosine kinase inhibitor, block phosphorylation of alpha-subunit of the Na+,K+-ATPase
isovaleric acid
-
isovaleric acid injection significantly inhibits Na+,K+-ATPase activity by 25% in cerebral cortex of rats 2 or 24 h after administration, while pre-treatment of rats with creatine completely prevents the inhibitory effects of isovaleric acid on Na+,K+-ATPase
jujuboside B
-
from mature seeds of Ziziphus jujube var. spinosa
L-homocysteine
-
inhibtory effect is reversed by alanine
L-phenylalanine
-
-
lauric acid
-
presence of 5 mM ATP, inhibitory above 0.25 mM. Presence of 0.05 mM ATP, stimulating up to 0.3 mM, inhibitory above
lavendustin A
-
tyrosine kinase inhibitor, block phosphorylation of alpha-subunit of the Na+,K+-ATPase
Lyn kinase
-
Lyn kinase directly binds to the Na+,K+-ATPase alpha3 subunit for regulation of activity
-
m-trifluoromethyl-diphenyl diselenide
-
i.e. (m-CF3C6H4Se)2, activity is restored by DTT
marinobufagenin
-
-
methyldigoxin
-
-
MTSET
-
[2-(trimethylammonium)ethyl]methanethiosulphonate bromide, inhibits mutants G803C, V805C
Na+
-
25% inhibition at 80 mmol/l
Na/K ATPase-alpha1-specific siRNA A1
-
0% decreases in expression of human alpha subunit in 293T cells
-
Na/K ATPase-alpha1-specific siRNA A1
-
-
-
Na/K ATPase-alpha1-specific siRNA A2
-
20% decreases in expression of human alpha subunit in 293T cells
-
Na/K ATPase-alpha1-specific siRNA A2
-
-
-
Na/K ATPase-alpha1-specific siRNA A3
-
20% decreases in expression of human alpha subunit in 293T cells
-
Na/K ATPase-alpha1-specific siRNA A3
-
-
-
Na/K ATPase-alpha1-specific siRNA A4
-
40% decreases in expression of human alpha subunit in 293T cells
-
Na/K ATPase-alpha1-specific siRNA A4
-
-
-
Na2CO3
-
inactivation
odoroside A
-
i.e. 3beta-O-(beta-D-diginosyl)-14-hydroxy-5beta,14beta-card-20(22)-enolide, isolated from the stems and twigs of Nerum oleander, inhibits the enzyme's ATPase activity
oleandrin
-
-
oleandrin
-
oleandrin treatment results in selective inhibition of human cancer cell growth but not rodent cell proliferation, which corresponds to the relative level of Na,K-ATPase alpha3 subunit protein expression. A correlation is observed between the ratio of alpha3 to alpha1 isoforms and the level of oleandrin uptake during inhibition of cell growth and initiation of cell death, the higher the alpha3 expression relative to alpha1 expression, the more sensitive the cell is to treatment with oleandrin
oleanolic acid
-
-
oleanolic acid
-
from whole plant of Prunella vulgaris with dried flowers
oleic acid
-
-
oligomycin
-
inhibits (Na+,K+)-ATPase reaction and Na+-ATPase reaction, has little effect on the K+-phosphatase reaction and can stimulate the ADP/ATP exchange reaction
oligomycin
-
not completely inhibits but decreases the rate of turnover of transport and of the hydrolysis reaction. Oligomycin affects the extracellular side of the system, Na+ on the cytoplasmic side of the system is necessary for the effect, oligomycin decreases the rate of transition from the Na+ form to the K+ form of the enzyme, but has no effect on the rate of the reverse reaction
Omeprazole
-
inhibit mutants G803C, T804C, V805C
orthovanadate
-
-
orthovanadate
-
-
orthovanadate
-
up to 67% inhibition in absence of NH4+
orthovanadate
-
up to 87% inhibition
Ouabain
-
enzyme from anterior intestine is ten-fold more sensitive than enzymes from pyloric caeca and posterior intestine
Ouabain
-
g-strophanthin
Ouabain
-
interaction is dependent on the conformation and phosphorylation state of the protein
Ouabain
-
-
Ouabain
-
inhibition of enzyme, enhancement of the acidification of the late endosome
Ouabain
-
up to 67% inhibition in absence of NH4+
Ouabain
-
up to 87% inhibition
Ouabain
-
-
Ouabain
-
-
Ouabain
-
-
Ouabain
-
-
Ouabain
-
ouabain does not affect TNF-alpha-induced mRNA expression but inhibits TNF-alpha-induced protein expression
Ouabain
-
complete inhibition at 0.001 mM
Ouabain
-
ouabain triggers an apoptotic cascade that involves NCX and CaMKII as a downstream effector. Ouabain simultaneously activates an antiapoptotic cascade involving PI3K/AKT which is however, insufficient to completely repress apoptosis. The NCX inhibitor KB-R7943 and by the CaMKII inhibitors, KN93 and AIP prevent ouabain-induced apoptosis without affecting inotropy. Ouabain produces in the cat at 25 nM a 43% decrease in cell viability due to apoptosis and necrosis
Ouabain
-
ouabain triggers an apoptotic cascade that involves NCX and CaMKII as a downstream effector. Ouabain simultaneously activates an antiapoptotic cascade involving PI3K/AKT which is however, insufficient to completely repress apoptosis.The NCX inhibitor KB-R7943 and by the CaMKII inhibitors, KN93 and AIP prevent ouabain-induced apoptosis without affecting inotropy
Ouabain
-
ouabain triggers an apoptotic cascade that involves NCX and CaMKII as a downstream effector. Ouabain simultaneously activates an antiapoptotic cascade involving PI3K/AKT which is however, insufficient to completely repress apoptosis. The NCX inhibitor KB-R7943 and by the CaMKII inhibitors, KN93 and AIP prevent ouabain-induced apoptosis without affecting inotropy. Ouabain produces in the rat at 0.002 mM a 43% decrease in cell viability due to apoptosis and necrosis
Ouabain
Q4H132
a cardiac glycoside derived from Strophanthus gratus, ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K+. Low-affinity ouabain-bound state due to antagonism between ouabain and K+. The closure of the binding cavity confers a high affinity, homology model for the high affinity state, structures, overview. Binding of sugar moiety and steroid core, overveiw
Ouabain
-
ouabain up to 1 mM decreases silkworm ATPase activity to 42% of the maximal ATPase activity in presence of 10 mM NaCl and 30 mM KCl
oubain
-
-
oubain
-
the IC50 value is higher in neonates than in children
oubain
-
-
oubain
-
K+ completely abolishes oubain binding to alpha1-beta1 isoenzymes. Residual oubain binding is still observed at high K+ concentrations for alpha2-beta1 and alpha3-beta1 complexes
oubain
-
-
oubain
-
-
oubain
-
-
oubain
-
two apparently different oubain binding sites
oubain
-
K+ protects against inhibition, probably due to phosphorylating effect
oubain
-
quantitative aspects of the interaction between oubain and the enzyme in vitro
oubain
-
half-maximal inhibition at 0.1 mM
p-chloro-diphenyl diselenide
-
i.e. (p-ClC6H4Se)2, activity is restored by DTT
p-methoxyl-diphenyl diselenide
-
i.e. (p-CH3OC6H4Se)2, activity is restored by DTT
palytoxin
-
-
palytoxin
-
mild, non-toxic, exposures to the Na+/K+-ATPase inhibitor palytoxin synergistically sensitizes the vulnerability of neurons to normally non-toxic concentrations of domoic acid, leaving NMDA receptor-mediated excitotoxic response unaltered. Palytoxin causes a voltage-sensitive Na+ channel-independent increase in intracellular Na+. Enhancement of the excitotoxic response to domoic acid by palytoxin is time-dependent and is not affected by gene expression inhibitors
Pb2+
-
inhibitory effect of Pb2+ on the transport cycle of the Na+,K+-ATPase, overview. Pb2+ inhibits cycling of the enzyme, but it does not affect cytoplasmic Na+ binding and release of Na+ ions at the extracellular side at concentrations below 0.010 mM
PCMB
-
-
perillyl alcohol
-
a monoterpene, inhibits Na/K-ATPase, non-competitive inhibition for Na+ and K+ and an uncompetitive inhibition for ATP in brain and kidney
perillyl alcohol
-
a monoterpene, inhibits Na/K-ATPase showing a noncompetitive inhibition profile to Na+ and K+ and an uncompetitive inhibition towards ATP. The generated electrochemical gradient is essential for a number of other cellular functions
polygalacic acid
-
from dried roots of Platycodon grandiflorum
PP1
-
Src kinase inhibitor
prostaglandin E2
-
PGE2
Prostaglandins
-
negative modulator
-
putrescine
-
-
reduced glutathione
-
extracellular and, or intracellular, inhibition of the transport activity of the Na-K pump
rottlerin
-
-
saikosaponin A
-
from dried roots of Bupleurum chinense or Bupleurum scorzonerifolium
sarsasapogenin
-
from dried roots of Anemarrhena asphodeloides
spermidine
-
-
spermine
-
-
strophanthidin
-
tyrosine kinase inhibitor, block phosphorylation of alpha-subunit of the Na+,K+-ATPase
strophantidine
-
-
superoxide
-
-
suramin
-
potent inhibitor, acts on the inside surface of the sodium pump
tetraethylammonium chloride
-
inhibition of pump current is independent on membrane potential
Tumor necrosis factor alpha
-
TNF-alpha, TNF-alpha affects the Na+-K+ pump via PGE2-dependent pathways
-
ursolic acid
-
from whole plant of Prunella vulgaris with dried flowers
vanadate
-
-
vanadate
-
20fold less sensitive to vanadate than alpha1 and 3; 20 times more sensitive to vanadate than alpha2
vanadate
-
-
vanadate
-
epigallocatechin-3-gallate reduces the affinity for vanadate, shifts the equilibrium of E1P and E2P toward E1P, and reduces the rate of the E1P to E2P transition
Yes kinase
-
regulator of the Na+,K+-ATPase activity
-
[PdCl(dien)]+
-
noncompetitive, affinity for binding in decreasing order: [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+. Addition of L-cysteine or glutathoione before exposure to Pd(II) complexes prevents inhibition
[PdCl(Me4dien)]+
-
noncompetitive, affinity for binding in decreasing order: [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+. Addition of L-cysteine or glutathoione before exposure to Pd(II) complexes prevents inhibition
-
[PdCl4]2-
-
noncompetitive, affinity for binding in decreasing order: [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+. Addition of L-cysteine or glutathoione before exposure to Pd(II) complexes prevents inhibition
Mg2+
-
IC50: 0.0008 mM; IC50: 0.0012 mM; IC50: 0.012 mM
additional information
-
decrease in extracellular pH inhibits Na+-K+ pump activity
-
additional information
-
not inhibitory: NH4+. At elevated concentrations of NH4+, enzyme is fully active and K+ cannot displace NH4+ from its exclusive binding sites
-
additional information
-
molecular docking and modelling, and inhibitory potencies of steroid-like compounds from Chinese medicinal products, used for promoting the blood circulation, with Na+,K+-ATPase, overview
-
additional information
-
odoroside A and ouabain potently reduce NF-kappaB-inducible de novo protein synthesis, largely due to its ability to block Na+-dependent transport of amino acids across the plasma membrane, but not to interfering with the translation machinery
-
additional information
-
physical training is effective against Na+,K+-ATPase enzyme activity inhibition, while fluid percussion injury induces a decrease in Na+,K+-ATPase activity in the ipsilateral cerebral cortex of sedentary animals
-
additional information
-
ETB receptor inhibits Na+-K+ ATPase activity by facilitating extracellular Ca2+ entry and Ca2+ release from endoplasmic reticulum
-
additional information
-
inhibitory potencies of cardenolide glycosides, isolated from the roots of Pergularia tomentosa, on Na+,K+-ATPase activity
-
additional information
Q4H132
cardiac glycosides are efficient inhibitors of the Na+,K+-ATPase
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-chloro-2,4-dinitrobenzene
-
increase of the hydrolytic activity of the Na/K ATPase
4-aminobutyric acid
-
hypothesis: stimulate Na+/K+ transport via specific receptor inputs
8-pCPT-CGMP
-
induces a concentration-dependent increase in pump current, activator of PKG
aldosterone
-
control of Na,K-ATPase activity and expression
Baclofen
-
hypothesis: stimulate Na+/K+ transport via specific receptor inputs
beta-catenin
-
expression of beta-catenin significantly enhances the ouabain-sensitive current of the endogeneous Na+/K+-ATPase. beta-Catenin does not significantly modify the retrieval of the Na+/K+ ATPase from the cell membrane. The stimulating effect of beta-catenin on both Na+/K+ ATPase and Na+-coupled glucose transporter SGLT1 activity is observed even in the presence of actinomycin D
-
dephostatin
-
-
desipramine
-
inhibitor of adrenalin uptake and antidepressive action. Treatment differentially enhances the activity of Na+K+-ATPase alpha isoforms
dexamethasone
-
postnatal treatment of lamb with 0.5 mg per kg results in 21.4% increase in Na+K+-ATPase activity and a 30.4% increase in catalytic subunit alpha1 expression in the cerebral cortex. Treatment is not associated with significant changes in subunit beta1 expression. In the kidney, dexamethasone treatment is not associated with significant changes in enzyme activity, or alpha-1- or beta-1-isoform expression
epinephrine
-
hypothesis: stimulate Na+/K+ transport via specific receptor inputs
glyburide
-
presence of 5 mM ATP, slightly stimulating up to 1 mM, inhibitory above. Presence of 0.05 mM ATP, stimulating at least up to 3 mM
Insulin
-
control of Na,K-ATPase activity and expression
-
interleukin-2
-
increases transport activity of the Na/K pump and the content of Na,K-ATPase alpha1 protein
-
K+
-
extracellular
lauric acid
-
presence of 5 mM ATP, inhibitory above 0.25 mM. Presence of 0.05 mM ATP, stimulating up to 0.3 mM, inhibitory above
Lyn kinase
-
Lyn kinase directly binds to the Na+,K+-ATPase alpha3 subunit for regulation of activity
-
NH4+
-
stimulation, following a single saturation curve. Synergistic effects of K+ and NH4+. Km value 4.5 mM
NH4+
-
stimulation, following a single saturation curve. Synergistic effects of K+ and NH4+. At elevated concentrations of NH4+, enzyme is fully active and K+ cannot displace NH4+ from its exclusive binding sites
NH4+
-
stimulation, synergistic effect of NH4+ and K+. Enzyme exhibits a single K+ binding site, NH4+ binding to a second, exlcusive site
norepinephrine
-
hypothesis: stimulate Na+/K+ transport via specific receptor inputs
Ouabain
-
activates Na/K-ATPase signaling complex
Ouabain
-
pretreatment of HK-2 cells with ouabain increases the Na+K+ATPase activity and inhibits the inhibitory effect of the D1 receptor on enzyme levels and activity, overview
polyclonal antibody pSSA 78
-
-
-
sodium
-
control of Na,K-ATPase activity and expression by intracellular Na+
sodium nitroprusside
-
SNP, NO donor, not a simple concentration-dependent effect on pump current
Vasopressin
-
control of Na,K-ATPase activity and expression
YC-1
-
activator of soluble guanylyl cyclase, sGC
Yes kinase
-
regulator of the Na+,K+-ATPase activity
-
monoclonal antibody SSA 78
-
-
-
additional information
-
half activated by a membrane potential of about -65 mV
-
additional information
-
increase in extracellular pH potentiates Na+-K+ pump activity
-
additional information
C0KXH0
the alpha-subunit is 2-fold more abundant in seawater-acclimated salt glands than in freshwater-acclimated glands. There is no increase in the specific activity of NKA in seawtaer-acclimated animals and the in vitro rate of oxygen consumption by salt gland slices from seawater-acclimated animals is not significantly different from that of Ffreshwater-acclimated animals
-
additional information
-
the distal tube and collecting duct cells show more intense Na+/K+-ATPase immunoreaction in freshwater eel than in seawater-acclimated eel
-
additional information
-
The Na+-affinity is higher in oxidative muscle compared with glycolytic muscle and in purified membranes from oxidative muscle compared with glycolytic muscle
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00151
ATP
-
Km1 value, plus gamma subunit, pH 7.4, 37C
0.00199
ATP
-
Km1 value, pH 7.4, 37C
0.05
ATP
-
pH 7.4, 37C, control
0.11
ATP
-
pH 7.4, 37C, neonatal hypothyroidism
0.242
ATP
-
Km2 value, pH 7.4, 37C
0.364
ATP
-
Km2 value, plus gamma subunit, pH 7.4, 37C
0.55
ATP
-
pH 7.4
1.5
ATP
-
low-affinity ATP hydrolyzing site, 25C, pH 7.5
0.7
K+
-
oxidative fiber, sarcolemmal membrane
1.3
K+
-
red gastrocnemius, total membranes, after exercise (running)
1.4
K+
-
white vastus lateralis, total membranes
1.5
K+
-
oxidative fiber, sarcolemmal membrane, after exercise (running)
1.6
K+
-
red gastrocnemius, total membranes
1.65
K+
-
apparent dissociation constant
1.9
K+
-
white vastus lateralis, total membranes, after exercise (running)
1.92
K+
-
apparent dissociation constant in the presence of 2 mM spermidine
3.1
K+
-
glycolytic fiber, sarcolemmal membrane
3.47
Na+
-
apparent dissociation constant
5.1
Na+
-
red gastrocnemius, total membranes
5.35
Na+
-
apparent dissociation constant in the presence of 2 mM spermidine
5.4
Na+
-
soleus, total membranes
6.1
Na+
-
oxidative fiber, sarcolemmal membrane
6.3
Na+
-
white vastus lateralis, total membranes, after exercise (running)
7.3
Na+
-
soleus, total membranes, after exercise (running)
7.5
Na+
-
red gastrocnemius, total membranes, after exercise (running)
8.3
Na+
-
extensor digitorum longus, total membranes, after exercise (running)
11.6
Na+
-
glycolytic fiber, sarcolemmal membrane, after exercise (running)
12.7
Na+
-
extensor digitorum longus, total membranes
14
Na+
-
glycolytic fiber, sarcolemmal membrane
15.8
Na+
-
oxidative fiber, sarcolemmal membrane, after exercise (running)
16.2
Na+
-
white vastus lateralis, total membranes
4
Na+/in
-
alpha1beta1 heterodimer, 37C, pH 7.4
5.5
Na+/in
-
alpha2beta1 heterodimer, 37C, pH 7.4
7.5
Na+/in
-
alpha1beta2 heterodimer, 37C, pH 7.4
8.6
Na+/in
-
posterior gill, juvenile crab acclimated to dilute seawater of 150 mOsm, pH 7.4
13
Na+/in
-
alpha2beta2 heterodimer, 37C, pH 7.4
21.3
Na+/in
-
anterior gill, sub-adult crab acclimated to dilute seawater of 150 mOsm, pH 7.4
4.6
K+
-
glycolytic fiber, sarcolemmal membrane, after exercise (running)
additional information
additional information
-
1.72 mmol/l with p-nitrophenyl phosphate as substrate, 0.165 mmol/l with ATP as substrate
-
additional information
additional information
-
changes in alphabetagamma stoichiometry of Na+K+-ATPase do not alter Km1 value for ATP, and slightly increase km, but Vmax decreases at both catalytic and regulatory sites
-
additional information
additional information
-
presence of phospholemman raises the K0.5 value for Na+ ions. Different functional effects depend on the degree of phosphorylation of phospholemman at residue S68
-
additional information
additional information
P05024
presence of phospholemman lowers the K0.5 value for Na+ ions by about 30%, but does not affect the turnover rate or Km value of ATP. Different functional effects depend on the degree of phosphorylation of phospholemman at residue S68
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2 - 8
K+
-
predicted, in the presence of 5.6 mM external K+
20.1
Na+/in
F8V2T6
maximum turnover rate per pump, pH not specified in the publication, 22C
25.5
Na+/in
Pareledone sp.
F8V2T5
maximum turnover rate per pump, pH not specified in the publication, 22C
3 - 6
K+
-
predicted, in the presence of 15 mM external K+
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.096
Ouabain
-
salinity-acclimated shrimp
0.117
Ouabain
-
25C, pH 7.5
0.176
Ouabain
-
freshwater shrimp
1.5
perillyl alcohol
-
pH 7.4, 37C, Na/K-ATPase-enriched A-127 cell extract
0.076
strophanthidin
-
IC50
26.6
tetraethylammonium chloride
-
half maximum inhibition of Na,K-pump current
4
benzyltriethylammonium chloride
-
half maximum inhibition of Na,K-pump current
additional information
additional information
-
0.05 mmol/l with ATP as inhibitor, 0.762 mmol/l with ouabain as inhibitor, 0.00025 mmol/l with o-vanadate as inhibitor
-
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
(1R,2R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-2,3a,11,11a-tetrahydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
pH 7.8, 37C
0.0012
(1R,2R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9-(hydroxymethyl)-15a-methyl-1-(5-oxo-2,5-dihydrofuran-3-yl)-2-(2-oxopropanoyl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
pH 7.8, 37C
0.0005
(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-13a-formyl-3a,11a-dihydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-11-yl beta-D-glucopyranoside
-
pH 7.8, 37C
0.0004
(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
pH 7.8, 37C
0.0005
(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9-(hydroxymethyl)-15a-methyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-7aH,13aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-13a-carbaldehyde
-
pH 7.8, 37C
0.0007
1,8,9-trihydroxy-3-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
37C, pH 7.4
0.055
12,20-dihydroxydammar-24-en-3-yl D-glucopyranoside
-
-
0.003
2,3-dihydroxy-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-6-one
-
37C, pH 7.4
0.0007
2,8,9-trihydroxy-3-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
37C, pH 7.4
0.006
2,9-dihydroxy-3,8-dimethoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
37C, pH 7.4
0.003
3,8,9-trihydroxy-2-methoxy-6H-[1]benzofuro[3,2-c]chromen-6-one
-
37C, pH 7.4
0.171
4,7-diacetoxy-14-hydroxydolast-1(15),8-diene
-
enzym preparation from kidney
0.0007
4-[(1R,3aS,5aS,6aR,7aS,9R,11R,11aS,12aR,13aR,15R,15aS)-3a,11,11a,15-tetrahydroxy-13a-(hydroxymethyl)-9,15a-dimethylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
pH 7.8, 37C
0.0004
4-[(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15aR)-3a,11,11a-trihydroxy-9,13a-bis(hydroxymethyl)-15a-methylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
pH 7.8, 37C
0.0003
4-[(1R,3aS,5aS,6aR,7aS,9S,11R,11aS,12aR,13aR,15R,15aS)-3a,11,11a,15-tetrahydroxy-9,13a-bis(hydroxymethyl)-15a-methylicosahydro-1H,7aH-cyclopenta[7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxin-1-yl]furan-2(5H)-one
-
pH 7.8, 37C
0.00009
8-methoxycoumestrol
-
isozyme alpha1beta1 Na,K-ATPase, pH 7.4, 30C
0.000587
beta-acetyldigoxin
-
isozyme alpha1beta1 Na,K-ATPase, pH 7.4, 30C
0.003
bufalin
-
-
0.000287
digitoxin
-
isozyme alpha1beta1 Na,K-ATPase, pH 7.4, 30C
0.000409
digoxin
-
isozyme alpha1beta1 Na,K-ATPase, pH 7.4, 30C
0.031
diphenyl diselenide
-
pH 7.4, 37C
0.2
epicatechin
-
pH 7.0, 37C
0.0008
epicatechin-3-gallate
-
pH 7.0, 37C
0.001
epigallocatechin-3-gallate
-
pH 7.0, 37C
0.006
m-trifluoromethyl-diphenyl diselenide
-
pH 7.4, 37C
0.000282
methyldigoxin
-
isozyme alpha1beta1 Na,K-ATPase, pH 7.4, 30C
0.0008
Mg2+
-
IC50: 0.0008 mM
0.0012
Mg2+
-
IC50: 0.0012 mM
0.012
Mg2+
-
IC50: 0.012 mM
0.0012
odoroside A
-
pH 7.0, 37C
0.115
oleic acid
-
enzym preparation from kidney
0.0001
Ouabain
-
-
0.00045
Ouabain
-
-
0.0016
Ouabain
-
enzym preparation from kidney
0.0016
Ouabain
-
pH 7.0, 37C
0.4
Ouabain
-
pH 7.4
0.006
p-chloro-diphenyl diselenide
-
pH 7.4, 37C
0.045
p-methoxyl-diphenyl diselenide
-
pH 7.4, 37C
0.0121
[PdCl(dien)]+
-
pH 7.4, 37C
0.0236
[PdCl(Me4dien)]+
-
pH 7.4, 37C
-
0.0225
[PdCl4]2-
-
pH 7.4, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.085
-
high salt diet
0.133
-
enzyme activity in HK-2 cells in presence of fenoldopam, pH not specified in the publication, temperature not specified in the publication
0.165
-
high normal diet
0.183
-
enzyme activity in HK-2 cells, pH not specified in the publication, temperature not specified in the publication
0.25
-
enzyme activity in ouabain-pretreated HK-2 cells in presence of fenoldopam, pH not specified in the publication, temperature not specified in the publication
0.267
-
enzyme activity in ouabain-pretreated HK-2 cells, pH not specified in the publication, temperature not specified in the publication
11.96
-
-
19.84
-
in reconstituted vesicles
32
-
tetraprotomer, pH 7.3, 37C
42
-
with p-nitrophenyl phosphate as substrate
65
-
diprotomer and protomer, 37C, pH 7.3
120
-
mutant K691A
175
-
mutant D714A
195
-
mutant K691R
259.1
-
with p-nitrophenolphosphate as substrate
575
-
mutant D714E
686.1
-
with ATP as substrate
700
-
with ATP as substrate
1105
-
wild-type
additional information
-
decrease in specific activity by 78.5% in neonatal hypothyroidism
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 7.4
-
assay at
7
-
assay at
7.2
-
storage solution for isolated cells
7.2
-
activity assay
7.2
-
assay at
7.4
-
assay at
7.4
-
optimal assay condition
7.4
-
assay condition
7.4
-
myocytes in the experimental chamber for measurement of Na+-K+ pump current
7.4
-
myocytes in the experimental chamber for measurement of Na+-K+ pump current
7.4
-
activity assay
7.4
-
assay at
7.5
-
optimal assay condition
7.5
-
in presence of 10 mM NaCl and 30 mM KCl
7.8
-
assay at
7.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4 - 7.8
-
variation of extracelluar pH for measurements of Na+-K+ pump activity
7
-
more than 90% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
optimal assay condition
22
-
assay at room temperature
23
-
myocytes in superfusion chamber
25
-
room temperature, activity assay
30
-
assay at
32
-
cells in temperature-controlled Lucite bath for patch-clamp experiments
35
-
optimal assay condition
37
-
assay conditions
37
-
assay condition
37
-
activity assay
37
-
myocytes in the experimental chamber for measurement of Na+-K+ pump current
37
-
myocytes in the experimental chamber for measurement of Na+-K+ pump current
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
additional information
F8V2T6
comparison of temperature sensitivity of the endogenous pump current of Na+/K+-ATPase in Antarctic Pareledone sp. and temperate Octopus bimaculatus. The voltage dependence of the pumps is equivalent. At room temperature the maximum turnover rate of the Antarctic pump is 25% higher than that of the temperate pump. In addition, the Antarctic pump exhibits a lower temperature sensitivity, leading to significantly higher relative activity at lower temperatures
additional information
Pareledone sp.
F8V2T5
comparison of temperature sensitivity of the endogenous pump current of Na+/K+-ATPase in Antarctic Pareledone sp. and temperate Octopus bimaculatus. The voltage dependence of the pumps is equivalent. At room temperature the maximum turnover rate of the Antarctic pump is 25% higher than that of the temperate pump. In addition, the Antarctic pump exhibits a lower temperature sensitivity, leading to significantly higher relative activity at lower temperatures
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
glioblastoma cells, A172 cells overexpress Na/K-ATPase alpha1 isoform in the caveolar structure
Manually annotated by BRENDA team
-
type II lung adenocarcinoma epithelial cells
Manually annotated by BRENDA team
-
male and female
Manually annotated by BRENDA team
-
electrogenic Na+K+-ATPase partially contributes to the ustained hyperpolarization of endothelial cells in response to acetylcholine
Manually annotated by BRENDA team
-
isolated mucosal cells of
Manually annotated by BRENDA team
-
cerebral cortex
Manually annotated by BRENDA team
-
capillary endothelium
Manually annotated by BRENDA team
-
little changes in enzyme alpha subunit isoform composition between summer and winter. Exposure to anoxia does not affect the activity of Na+K+-ATPase, but there is a 150fold extension in brain anoxia tolerance by seasonal changes in energy supply-demand ratio. Enzyme shows 10times lower catalytic activity in winter than in summer
Manually annotated by BRENDA team
-
mainly alpha2- and alpha3 isoform
Manually annotated by BRENDA team
-
cerebral, ipsilateral cortex
Manually annotated by BRENDA team
-
CACO-2BBE cell
Manually annotated by BRENDA team
-
rodent cancer cells lack discernable expression of the alpha3 subunit Na,K-ATPase isoform
Manually annotated by BRENDA team
-
cerebellar granule cells
Manually annotated by BRENDA team
-
inner ear
Manually annotated by BRENDA team
-
red portion of the muscle
Manually annotated by BRENDA team
-
acclimation to dilute seawater induces increased expression of Na+K+-ATPase and enzyme activity, with the increase being less in juveniles than in larger crabs. Juveniles maintain osmotic and ionic homeostasis by the expression and utilization of extremely high levels of gill Na+K+ATPase, in posterior, as well in anterior, gills
Manually annotated by BRENDA team
-
following acclimation in dilute seawater, specific activity of Na+K+-ATPase is progressively increased up to 3.9fold. Increased enzyme activity may be modulated by the changed proportion of fatty acids in the purified membranes of posterior gills. Long-term acclimation to dilute seawater results in increase in metallothionein content in posterior gill
Manually annotated by BRENDA team
-
Na+K+-ATPase constitutes 80% of total ATPase activity
Manually annotated by BRENDA team
-
neither osmotic pressure, Na+K+-ATPase activity, nor free amino acids are affected by diets rich/low in highly unsaturated fatty acids. Higher water content in gills of shrimp exposed to low salinty is counteracted by increased content in highly unsaturated fatty acids
Manually annotated by BRENDA team
-
of the input layer of cerebellar cortex
Manually annotated by BRENDA team
-
Na+K+-ATPase activity is positively regulated via an N-terminal phosphorylation site that is necessary for correct heart morphogenesis to occur, and maintenance of Zonula occludens-1 junction belts requires ion pump activity
Manually annotated by BRENDA team
-
differential distribution of enzyme alpha subunit isoforms in subicular interneurones and pyramidal cells. While ATP1A3-isoforms regulate sodium and potassium homeostasis in subicular interneurones, ATPA1-isoforms assume this function in pyramidal cells
Manually annotated by BRENDA team
-
proximal tubule cell line
Manually annotated by BRENDA team
-
pyloric caeca, posterior intestine, anterior intestine
Manually annotated by BRENDA team
-
medulla
Manually annotated by BRENDA team
-
medulla, macula densa
Manually annotated by BRENDA team
-
outer medulla
Manually annotated by BRENDA team
-
alpha1-isoform
Manually annotated by BRENDA team
-
from normotensive patients who have unilateral nephrectomy because of renal carcinoma or trauma
Manually annotated by BRENDA team
-
isozyme alpha1beta1 Na,K-ATPase
Manually annotated by BRENDA team
-
light microscopic immunocytochemistry detects Na+/K+-ATPase along the renal tubules and collecting ducts. Na+/K+-ATPase is distributed on the basal infoldings of first and second segments of the proximal tubule, and distal tube cells. The distal tube and collecting duct cells show more intense Na+/K+-ATPase immunoreaction in freshwater eel than in seawater-acclimated eel
Manually annotated by BRENDA team
-
muscle cell line, A-769662 inhibits the Na+-K+-ATPase cell surface abundance in L6 cells by decreasing the phosphorylation of the alpha-subunit
Manually annotated by BRENDA team
-
at fifth instar feeding stage
Manually annotated by BRENDA team
-
peripheral muscle band
Manually annotated by BRENDA team
-
pulmonary artery smooth muscle
Manually annotated by BRENDA team
-
study on enzyme isoforms in muscle in three consecutive days of exercise followed by 3 days of recovery. Increases in subunit isoforms alpha1, alpha2, alpha3 by 46%, 42%, and 31% are observed at recovery day 1, respectively. Subunit isoforms beta1 and beta2 increase by 19% and 28% at recovery day 1, whereas isoform beta3 increase by 18% at recovery day 2. with exception of isoforms alpha 2 and alpha 3, the increases persisted at recovery day 3. The increases in subunit expression are not accompanied by increases in the maximal catalytic activity
Manually annotated by BRENDA team
-
epicardial, midmyocardial, endocardial ventricular myocytes
Manually annotated by BRENDA team
-
ventricular myocyte
Manually annotated by BRENDA team
-
ventricular myocyte
Manually annotated by BRENDA team
-
ventricular myocyte. Patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continously in the tramsverse tubules alone. Isoform alpha3 is expressed prominently in the intercalated discs. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc. Subunit isoform alpha1 and alpha2 form heterodimers with subunit isoform beta1 and alpha3 with beta2
Manually annotated by BRENDA team
-
ventricular myocyte. Patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continuously in the transverse tubules alone. Isoform alpha3 is expressed slightly. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc. Subunit isoform alpha1 and alpha2 form heterodimers with subunit isoform beta1 and alpha3 with beta2
Manually annotated by BRENDA team
-
ventricular myocyte. Subunit isoform alpha 2 accounts for 29.5% of the cation current, and the low-affinity subunit isoform alpha 1 accounts for 70.5% of current. The functional density of the enzyme is significantly higher in t-tubules compared to external sarcolemma. Subunit isoform alpha2 is enriched in t-tubules, while isoform alpha1 is almost uniformly distributed between the t-tubules and external sarcolemma
Manually annotated by BRENDA team
-
enzyme activity is well-maintained in the dissociated neostriatal neurons
Manually annotated by BRENDA team
-
presence of Na+/K+-ATPAse
Manually annotated by BRENDA team
-
mesencephalic trigeminal neurons having numerous splines
Manually annotated by BRENDA team
-
oubain-resistant mutant Na+/K+-ATPase is expressed in Xenopus oocytes by microinjection of mRNA coding for the alpha-subunit and the beta-subunit of the protein
Manually annotated by BRENDA team
-
expression of different isoenzymes in Xenopus oocytes
Manually annotated by BRENDA team
-
a pancreatic cancer cell line
Manually annotated by BRENDA team
-
a pancreatic cancer cell line
Manually annotated by BRENDA team
-
differential distribution of enzyme alpha subunit isoforms in subicular interneurones and pyramidal cells. While ATP1A3-isoforms regulate sodium and potassium homeostasis in subicular interneurones, ATPA1-isoforms assume this function in pyramidal cells
Manually annotated by BRENDA team
dogfish
-
-
Manually annotated by BRENDA team
-
existence of at least two isoforms of the pump in the horizontal cells
Manually annotated by BRENDA team
additional information
-
method for histochemical localization of the enzyme
Manually annotated by BRENDA team
additional information
-
expression analysis of isozymes alpha1 and alpha3
Manually annotated by BRENDA team
additional information
-
enzyme is not detected in skeletal muscle or the dorsal vessel
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
of gill chloride cell. Acclimation from fresh water to seawater is accompanied by 8fold increase in enzyme activity and 3fold increase in enzyme protein number. Enzyme activity in seawter fish is negatively correlated with basolateral membrane cholesterol content and positively correlated with phosphatidylethanolamine and linoleic acid content. Activity in freshwater fish is not correlated to any membrane lipid parameter
Manually annotated by BRENDA team
-
enzyme is involved in endosomal pH regulation
Manually annotated by BRENDA team
-
uneven distribution of alpha1 and beta1 subunits in early and late endosome suggesting different internalization routes
Manually annotated by BRENDA team
-
rapid translocation for short-term regulation between membrane and intracellular compartments
Manually annotated by BRENDA team
-
components of the sodium pump are membrane intercalated and protrude from the membrane surface
Manually annotated by BRENDA team
-
light caveolar membranes contain 30-40% of alpha1 subunits and 80-90% of beta1 subunits. Subunits are associated with caveolin oligomers
Manually annotated by BRENDA team
-
enzyme is distributed in a polarized manner in a restricted domain of the plasma membrane and polarity depends on interactions between the beta-subunits of Na+/K+-ATPases located on neighboring cells. These beta-subunits have sufficient proximity and affinity to permit a direct interaction, without requiring any additional extracellular molecules to span the distance. The beta-beta interaction is species-specific
Manually annotated by BRENDA team
C0KXH0
lateral and basal membrane of secretory cells
Manually annotated by BRENDA team
-
patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continously in the tramsverse tubules alone. Isoform alpha3 is expressed prominently in the intercalated discs. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc
Manually annotated by BRENDA team
-
patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continuously in the transverse tubules alone. Isoform alpha3 is expressed slightly. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc
Manually annotated by BRENDA team
-
subunit isoform alpha2 abundance is higher in the t-tubules than in the surface sarcolemma. The isoform is functinally coupled to the Na+/Ca2+-exchanger and can regulate Ca2+ handling without changing global concentration of Na+
Manually annotated by BRENDA team
-
the functional density of the enzyme is significantly higher in t-tubules compared to external sarcolemma. Subunit isoform alpha2 is enriched in t-tubules, while isoform alpha1 is almost uniformly distributed between the t-tubules and external sarcolemma
Manually annotated by BRENDA team
-
subunit isoform alpha2 abundance is higher in the t-tubules than in the surface sarcolemma. The isoform is functinally coupled to the Na+/Ca2+-exchanger and can regulate Ca2+ handling without changing global concentration of Na+
Manually annotated by BRENDA team
-
the functional density of the enzyme is significantly higher in t-tubules compared to external sarcolemma. Subunit isoform alpha2 is enriched in t-tubules, while isoform alpha1 is almost uniformly distributed between the t-tubules and external sarcolemma
Manually annotated by BRENDA team
-
neuronal vesicles in axons associated with the peripheral muscle layer
Manually annotated by BRENDA team
-
patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continously in the tramsverse tubules alone. Isoform alpha3 is expressed prominently in the intercalated discs. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc
-
Manually annotated by BRENDA team
-
patchy presence of subunit isoform alpha1 in the transverse tubules and surface sarcolemma, isoform alpha2 is distributed continuously in the transverse tubules alone. Isoform alpha3 is expressed slightly. Subunit isoform beta1 is located in the transverse tubules and surface sarcolemma, and isoform beta2 is mainly located in the intercalated disc
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7000
-
gamma subunit: 6500-7500 Da, identified in kidney tissue
677133
35000
-
beta subunit, glycoprotein, 35-55kDa
673231
35000
-
beta subunit
677133
55000
-
glycosylated beta subunit
675719
60000
-
beta1 subunit, SDS-PAGE, silver staining
675880
100000
-
alpha1 subunit, SDS-PAGE, silver staining
675880
110000
-
alpha subunit, 110-113kDa
673231
110000
-
alpha subunit
675719
110000
-
SDS PAGE, Western blot
677142
112000
-
alpha subunit
677133
155000
-
non-denaturing PAGE
700145
250000 - 300000
-
radiation inactivation , gel filtration
246961
379000
shark
-
equilibrium sedimentation
246967
380000
-
equilibrium centrifugation
246961
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 100000, alpha-subunit, + x * 38000, beta-subunit, the ratio of alpha: beta is 1:1
?
-
x * 111817, calculated from nucleotide sequence
dimer
-
alpha subunit, main subunit - beta subunit, glycoprotein
dimer
-
alphabeta, minimal functional unit, aggrgation of protomeric units is a common observation
dimer
-
catalytic alpha1 subunit
dimer
-
heterodimer, alpha and beta subunit
dimer
-
heterodimer, catalytic alpha subunit, beta subunit
heterodimer
-
alphabeta
heterodimer
-
progesterone binding to the ouabain binding site of the alpha-subunit of Na/K-ATPase
heterodimer
-
1 * 110000 + 1 * 45000, alpha2 + beta1
heterodimer
-
alpha/beta, alpha1: 110000 Da, alpha2: 105000 Da, alpha3: 110000 Da, beta1: 55000 Da, beta2: 55000 Da, beta3: not detected, SDS-PAGE/Western blot, associated gamma-subunit may have a regulatory role
trimer
-
alphabetagamma
heterodimer
-
alpha/beta: subunit alpha1, alpha2, alpha3, beta1, beta2 expressed in skeletal muscle
additional information
-
differential distribution of enzyme alpha subunit isoforms in subicular interneurones and pyramidal cells. While ATP1A3-isoforms regulate sodium and potassium homeostasis in subicular interneurones, ATPA1-isoforms assume this function in pyramidal cells
additional information
-
enzyme directly associates with arrestin 2 and 3, G-protein-coupled receptor kinase 2 and 3, protein 14-3-3 epsilon, and spinophilin. Presence of spinophilin blocks the association with arrestin 2 and 3, G-protein-coupled receptor kinase 2 and 3, and protein 14-3-3 epsilon. In COS cells overexpressing arrestin, the Na+K+ATPase is redistributed to intracellular compartments
additional information
-
in presence of acetate anion, and, in decreasing order, NH4+ propionate, Rb+ propionate, K+ propionate, and Tl+ propionate, enzyme forms a tetraprotomer (alphabeta)4, consuming (alphabeta)2 diprotomer and (alphabeta) protomer. By exposure to 25C, the tetraprotomer shows 34% dissociation to diprotomer
additional information
P05024
presence of transmembrane protein phospholemman in a complex with Na+K+-ATPase alpha/beta subunits markedly stabilizes
additional information
-
subunit isoforms alpha1 and alpha2 form heterodimers with subunit isoform beta1 and alpha3 with beta2 in the ventricluar myocyte
additional information
-
the enzyme gamma subunit is located adjacent to the M2-M6-M9 pocket of the alpha subunit at the transmembrane-extracellular interface. During the E1 to E2 transition, there is no relative change in distance between the alpha and gamma subunits but there is a relative change in distance between the beta and gamma subunits
additional information
-
alpha-subunit: 115000, SDS-PAGE /Western blot
additional information
-
alpha1-subunit: 112000, beta1-subunit: 48000, SDS-PAGE /Western blot analysis
additional information
-
Na,K-ATPase peptide mapping, identification of Na/K-ATPase-derived, membrane-bound peptide , that acts as an inhibitor for protein kinases, ND1 acts as a Src-interacting domain from the Na/K-ATPase alpha1 subunit, overview. The ND2 reveals that the N terminus of ND2 is highly exposed and does not contribute to ATP binding
additional information
-
heterodimers containing the beta1 isoform have a higher N+-affinity than heterodimers containing the beta2 isoform. Dimers with alpha1 isoform are responsible for approximately 36% of the total Na+/K+ATPase activity. Heterodimers containing the alpha1 isoform have a higher Na+-affinity than heterodimers containing the alpha2 isoform
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
Na+K+-ATPase activity is positively regulated via an N-terminal phosphorylation site that is necessary for correct heart morphogenesis to occur, and maintenance of Zonula occludens-1 junction belts requires ion pump activity
phosphoprotein
-
phosphorylation of catalytic alpha1-subunit
glycoprotein
-
the beta subunit is a glycoprotein
glycoprotein
-
beta subunit
side-chain modification
-
required for activity, removal of lipids leads to inactivation and readdition of the lipids results in reactivation of the enzyme
phosphoprotein
-
enzyme is phopsphorylated by G-protein-coupled receptor kinase in vitro on its large cytoplasmic loop
phosphoprotein
-
phosphorylation of the alpha-subunit triggers the Na+-K+-ATPase activity in endocytosis and exocytosis, A-769662 inhibits the Na+-K+-ATPase cell surface abundance in L6 cells by decreasing the phosphorylation of the alpha-subunit independently of the AMP kinase activity
phosphoprotein
-
52% of the accumulating phosphorylated Na+K+-ATPase is not via acyl-phosphate formation. Gamma subunit is phosphorylated by endogenous kinases and by commercial catalytic subunit of protein kinase A. Phosphorylation of the gamma subunit increases its capacity to stimulate ATP hydrolysis
phosphoprotein
-
reversible phosphorylation of theenzyme during reaction
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
strucutural modeling of enzyme. Residue F785 participates in a hydrophobic network between three transmembrane segments. Residue T618 is located in the cytoplasmic part of the molecule near the catalyitc site
-
two-stage model of interaction between cardiac transmembrane protein phospholemman and the Na+/K+-ATPase involving phospholemman-ATPase interaction and subsequent formation of an unstable phospholemman trimer, which readily interacts with surrounding ATPase molecules
-
refinement to 9-11 A
-
Na+,K+-ATPase with bound inhibitor ouabain fixed in a state analogous to E2-2K+Pi with a stable phosphate analog MgF4 2-, usage of the crystallization buffer containing 25% glycerol w/v, 5% v/v MPD, 100 mM potassium acetate, 10 mM KCl, 4 mM MgCl2, 4 mM KF, 0.1 mM EGTA, 10 mM glutathione, 0.002 mg/mL 2,6-di-t-butyl-p-cresol, 20 mM MES-Tris, pH 7.0, and 40% w/v PEG 3000, soaking of the crystals in a buffer containing 20 mM ouabain for 5 h, X-ray diffraction structure determination and analysis at 2.8 A resolution
Q4H132
4.6 A resolution crystal structure in its phosphorylated form stabilized by high affinity binding of ouabain. Ouabain binds to a site formed at transmembrane segments alphaM1-alphaM6, plugging the ion pathway from the extracellular side. The A domain has rotated in response to phosphorylation and alphaM1-2 move towards the ouabain molecule, providing for high affinity interactions and closing the ion pathway from the extracellular side
P05024
purified native enzyme, X-ray diffraction structure determination and analysis at 2.0-3.0 A resolution, molecular replacement, the NKA monomer is divided into four separate domain masks
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivated by freezing at -20-25C in imidazole-EDTA without cryoprotectants
-
EDTA and histidine stabilize the E2 enzyme conformation
-
inactivated by freezing at -20-25C in imidazole-EDTA without cryoprotectants
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, microsomal fraction, after 2 months no loss in activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution with phospholipid dioleoyl-phosphatidylcholine
-
native enzyme partially from brain and kidney
-
native enzyme from kidney cortex, recombinant His-tagged enzyme from HEK-293 cells by nickel affinity chromatography
-
treatment of membranes by KCl leaves the enzyme intact, while Na2CO3 is inactivating
-
-
shark
-
native enzyme from kidney outer medulla, GST-tagged Na/K-ATPase-derived, membrane-bound peptide and ND1 and ND2 domains from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
-
recombinant alpha/beta subunits in complex with phospholemman
P05024
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Xenopus oocytes
-
alpha-subunit H1-H2 region
-
expression in Xenopus laevis
F8V2T6
expressed in HeLa cells
-
expressed in Xenopus laevis oocyten; expressed in Xenopus oocyten
-
expression in Xenopus laevis
-
expression of subunit alpha 1 in Saccharomyces cerevisiae together with dog subunit beta1
-
expression in Xenopus laevis
Pareledone sp.
F8V2T5
alpha-subunit, expression in Escherichia coli
-
expression in COS cells and LLC-PK1 cells
-
expression in HeLa cells
-
expression of alpha subunit in HeLa cell, with rat transmembrane protein phospholemman
-
expression of His-tagged enzyme in HEK-293 cells
-
expression in Xenopus laevis oocyte
-
in pSD5 vector, expression of proteins in Xenopus laevis oocytes
-
cloning of a ATPase alpha subunit
-
expression in Pichia pastoris, with human transmembrane protein phospholemman
P05024
GST-tagged Na/K-ATPase-derived, membrane-bound peptide , and ND1 and ND2 domains in Escherichia coli strain BL21(DE3)
-
expression in Xenopus laevis
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
NKA gene expression is elevated in the salt glands of seawater-acclimated crocodiles compared to freshwater-acclimated animals
C0KXH0
expression of Na+, K+-ATPase alpha-subunit isoforms alpha-1a and alpha-1b in relationship with salinity acclimation. Transfer of freshwater acclimated fish to seawater results in a marked reduction in alpha-1a expression within 24 h and a significant increase in alpha-1b expression with maximum levels attained 7 days after the transfer. Transfer of seawater-acclimated fish to freshwater induces a marked increase in alpha-1a expression within 2 days, while alpha-1b expression decreases significantly after 14 days. Hypophysectomy results in a virtual shutdown of alpha-1a mRNA expression in both freshwater- and seawtaer-acclimated fish, whereas no significant effect is observed in alpha-1b expression. Replacement therapy by ovine prolactin fully restores alpha-1a expression in freshwater-acclimated fish, while cortisol has a modest, but significant, stimulatory effect on alpha-1a expression. The mRNA expression of fxyd-11, a regulatory Na+,K+-ATPase subunit,is transiently enhanced during both freshwater and seawater acclimation
Q9YH26
dexamethasone and other glucocorticoids inhibit the Na+,K+-ATPase expression in the lens. Glucocorticoid-antagonist RU486 inhibits the decrease of the expression of Na+, K+-ATPase alpha1 subunit induced by dexamethasone
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D409E
-
phosphorylation site of alpha-subunit, inactive pump
R669Q
-
ATP binding site of alpha-subunit, inactive pump
F785L
-
mutation associated with familial rapid-onset dystonia parkinsonism, leads to functionally altered, but active, Na+K+-pumps with reduced apparent affinity for cytoplasmic Na+. Defect in the interaction of the E1 form of enzyme with Na+, and the E1-E2 equilibrium is not displaced. K+ interaction at the external activating sites of E2P phosphoenzyme is normal. The affinity for ouabain is significantly reduced
F785L/L786F
-
aromatic function of F785 is critical for Na+ and ouabain binding
T618M
-
mutation associated with familial rapid-onset dystonia parkinsonism, leads to functionally altered, but active, Na+K+-pumps with reduced apparent affinity for cytoplasmic Na+. The Na+-affinity is reduced because of displacement of the conformational equilibrium in favor of the K+-occluded E2 form. K+ interaction at the external activating sites of E2P phosphoenzyme is normal
C911S/C964A/Q111R/N122D
-
alpha-subunit: mutant without extracellularly exposed cysteine residues (911, 964) and with reduced ouabain sensitivity (111, 122)
C911S/C964S/Q111R/N122D
-
alpha1-subunit mutant without extracellularly exposed cysteine residues (911, 964), and with reduced ouabain sensitivity (111, 122)
D714A
-
insensitive to palytoxin
D714E
-
the IC50 of the palytoxin-induced K+ efflux is 4fold higher than in cells expressing the wild-type enzyme
D714R
-
insensitive to palytoxin
E779A
-
15fold increase in K+ concentration that half-maximally activates Na,K-pump current at 0 mV in extracellular Na+-free solutions
G848F
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
G848W
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
K691A
-
insensitive to palytoxin
K691D
-
insensitive to palytoxin
K691R
-
the EC50 of the palytoxin-induced K+ efflux is 7fold higher than in cells expressing the wild-type enzyme
N122D
-
membrane potential and K+ dependence similar to wild-type Na,K-ATPase
Q111R
-
membrane potential and K+ dependence similar to wild-type Na,K-ATPase
Q849G
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
Q849H
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
Q849W
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
S62C
-
beta-subunit: mutation for site-directed fluorescence labeling without impairing enzyme function, beta1-subunit mutant with Cys for site-directed fluorescence labeling
S62C/N158Q/N193Q/N265Q
-
beta-subunit: mutation for site-directed fluorescence labeling without impairing enzyme function (62) and mutations in all N-glycosylation sites of the beta1-ectodomain (158, 193, 265)
S62C/Y39F/Y43F
-
beta1-subunit mutant with Cys for site-directed fluorescence labeling (62), and with a shift of the conformational equilibrium (39,43)
S62C/Y39S/Y43S
-
beta1-subunit mutant with Cys for site-directed fluorescence labeling (62), and with a shift of the conformational equilibrium (39,43)
S62C/Y39W/Y43W
-
beta1-subunit mutant with Cys for site-directed fluorescence labeling (62), and with changed apparent rate constant for reverse binding of extracellular Na+ (39, 43)
S775A
-
155fold increase in K+ concentration that half-maximally activates Na,K-pump current at 0 mV in extracellular Na+-free solutions
Y847W
-
alpha1-subunit, located in transmembrane domain 7 (alpha/beta interface)
A330C
-
difference between K+-induced and ouabain-sensitive I/V curve especially in the negative voltage range, negative slope of the I/V curve of the ouabain-sensitive current in the low and positive membrane potential range
A330C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
A338C
-
difference between K+-induced and ouabain-sensitive I/V curve especially in the negative voltage range
A338C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
C111S
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
C111S
-
control
C111S
-
used as control
E334C
-
negative slope of the I/V curve of the ouabain-sensitive current in the low and positive membrane potential range, K+-activated current with an amplitude half of the oubain-sensitive current in the high negative membrane potential range
E334C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
F323C
-
small ouabain-sensitive current over the whole membrane potential range, significant K+-induced inward curve mostly at negative membrane potential range
F323C
-
K+ induced current, I_K in nA, lower than control(negativ) - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
G326C
-
inhibition by 2-aminoethyl-methanethiosulfonate
G326C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
G335C
-
identical and strongly voltage-dependent I/V relationship of the K+-induced and ouabain sensitive currents
G335C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
G803C
-
the effect of cysteine mutations on the K+ activated and ouabain-sensitive currents, the effect of acid pH and omeprazole, the effect of MTSET on Na+, K+-ATPase cysteine mutants and the effect of MTSET on the voltage-dependent kinetics of activation by extracellular K+ is measured.
I322C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
I322C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
I325C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
I325C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
I327C
-
difference between K+-induced and ouabain-sensitive I/V curve especially in the negative voltage range
I327C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
I328C
-
negative slope of the I/V curve of the ouabain-sensitive current in the low and positive membrane potential range
I328C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, higher than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
L324C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
L324C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, similar to control
L336C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
L336C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, higher than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
L337C
-
K+ induced current, I_K in nA, lower (negative) than control - ouabain-sensitive current, I_ouab in nA, lower (negative) than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
L344C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
L344C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, higher than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
L802C
-
the effect of cysteine mutations on the K+ activated and ouabain-sensitive currents, the effect of acid pH and omeprazole, the effect of MTSET on Na+, K+-ATPase cysteine mutants and the effect of MTSET on the voltage-dependent kinetics of activation by extracellular K+ is measured.
N331C
-
difference between K+-induced and ouabain-sensitive I/V curve especially in the negative voltage range
N331C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, similar to control
P333C
-
inhibition by 2-aminoethyl-methanethiosulfonate
P333C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
P801C
-
the effect of cysteine mutations on the K+ activated and ouabain-sensitive currents, the effect of acid pH and omeprazole, the effect of MTSET on Na+, K+-ATPase cysteine mutants and the effect of MTSET on the voltage-dependent kinetics of activation by extracellular K+ is measured.
T339C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower control
T341C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, similar to control - membrane conductance induced by palytoxin, G_PTX in mikroS, lower than control
T804C
-
the effect of cysteine mutations on the K+ activated and ouabain-sensitive currents, the effect of acid pH and omeprazole, the effect of MTSET on Na+, K+-ATPase cysteine mutants and the effect of MTSET on the voltage-dependent kinetics of activation by extracellular K+ is measured.
V321C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
V321C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, similar to control
V329C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
V329C
-
K+ induced current, I_K in nA, lower than control - ouabain-sensitive current, I_ouab in nA, lower than control - membrane conductance induced by palytoxin, G_PTX in mikroS, similar to control
V332C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
V332C
-
K+ induced current, I_K in nA, similar to control - ouabain-sensitive current, I_ouab in nA, similar to control - membrane conductance induced by palytoxin, G_PTX in mikroS, similar to control
V340C
-
little voltage dependence in the low membrane voltage range and a slight voltage dependence in the high negative membrane voltage range
V340C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, higher than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
V342C
-
K+ induced current, I_K in nA, higher than control - ouabain-sensitive current, I_ouab in nA, higher than control - membrane conductance induced by palytoxin, G_PTX in mikroS, higher than control
V805C
-
the effect of cysteine mutations on the K+ activated and ouabain-sensitive currents, the effect of acid pH and omeprazole, the effect of MTSET on Na+, K+-ATPase cysteine mutants and the effect of MTSET on the voltage-dependent kinetics of activation by extracellular K+ is measured.
D813C
-
decrease in cation/anion selectivity, which is grossly impaired after treatment with 2-trimethylammonium-ethyl-methanethiosulphonate
D817C
-
highly cation-selective pump-channel, no response to modification by 2-trimethylammonium-ethyl-methanethiosulphonate
E321C
-
reaction with 2-trimethylammonium-ethyl-methanethiosulphonate does not decrease cation current
E336C
-
decrease in cation/anion selectivity, which is transformed from cation-selective to anoin-selective after treatment with 2-trimethylammonium-ethyl-methanethiosulphonate
E788C
-
highly cation-selective pump-channel, no response to modification by 2-trimethylammonium-ethyl-methanethiosulphonate
G805C
-
reaction with 2-trimethylammonium-ethyl-methanethiosulphonate or with 2-aminocarbonyl-ethyl-methanethiosulphonate does not decrease cation current
N785C
-
highly cation-selective pump-channel, no response to modification by 2-trimethylammonium-ethyl-methanethiosulphonate
T806C
-
cation current is diminished after reaction with 2-trimethylammonium-ethyl-methanethiosulphonat and 7fold decreased after reaction with 2-aminocarbonyl-ethyl-methanethiosulphonate
F785Y
-
aromatic function of F785 is critical for Na+ and ouabain binding
additional information
-
knockdown of alpha3 isoform expression by alpha3 siRNA, and increasing alpha1 isoform expression by transient transfection of alpha1 cDNA in Panc-1 cells
additional information
-
reduction of Na+, K+-ATPase alpha1 subunit expression by siRNA transfection
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
the positive inotropic effect produced by Na+/K+-ATPase inhibition is used for the treatment of heart failure
medicine
-
analysis of mutations F785L and T618M associated with familial rapid-onset dystonia parkinsonism
medicine
-
study on enzyme isoforms in muscle in three consecutive days of exercise followed by 3 days of recovery. Increases in subunit isoforms alpha1, alpha2, alpha3 by 46%, 42%, and 31% are observed at recovery day 1, respectively. Subunit isoforms beta1 and beta2 increase by 19% and 28% at recovery day 1, whereas isoform beta3 increase by 18% at recovery day 2. with exception of isoforms alpha 2 and alpha 3, the increases persisted at recovery day 3. The increases in subunit expression are not accompanied by increases in the maximal catalytic activity
medicine
-
the positive inotropic effect produced by Na+/K+-ATPase inhibition is used for the treatment of heart failure
medicine
-
in induced hyperthyroidism, Na+K+-ATPase activity is significantly decreased, whereas acetylcholinesterase activity is increased in the hippocampus. Na+K+-ATPase activity of the frontal cortex remains unchanged in hyperthyroidism. In hypothyroid rat, Na+K+-ATPase activity is significanlty decreased in both the frontal cortex and the hippocampus, whereas acetylcholinesterase activity is decreased in the frontal cortex and increased in the hippocampus. Mg2+-ATPase activity remains unchanged in both hyper- and hypothyroid rat brain
medicine
-
neonatal hypothyroidism results in a generalized decrease in Vmax with ATP, Na+, K+ and Mg2+ together with an increase in the Km value for ATP, appearance of a low affinity component for Na+ and allosteric characteristic for the Mg2+-dependent activity at high concentrations of Mg2+
medicine
-
the positive inotropic effect produced by Na+/K+-ATPase inhibition is used for the treatment of heart failure