Information on EC 3.6.3.7 - Na+-exporting ATPase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
3.6.3.7
-
RECOMMENDED NAME
GeneOntology No.
Na+-exporting ATPase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Na+/in = ADP + phosphate + Na+/out
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
transmembrane transport
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (Na+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme from yeast is involved in the efflux of Na+, with one ion being exported per ATP hydrolysed.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
strain ATCC 43024
-
-
Manually annotated by BRENDA team
acu1
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
alpha subunit
UniProt
Manually annotated by BRENDA team
DhENA1, DhENA2
-
-
Manually annotated by BRENDA team
microconidia
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain DSM 2382
-
-
Manually annotated by BRENDA team
MHOM/BR/75/Josefa strain
-
-
Manually annotated by BRENDA team
MHOM/BR/75/Josefa strain
-
-
Manually annotated by BRENDA team
+AHw-LDCA1, present as a single copy gene+AHwAfA-
SwissProt
Manually annotated by BRENDA team
strain DSM 3647
-
-
Manually annotated by BRENDA team
acu1
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
NcENA1
-
-
Manually annotated by BRENDA team
NcENA1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
PpENA1 ATPase
-
-
Manually annotated by BRENDA team
ENAI
SwissProt
Manually annotated by BRENDA team
frog
-
-
Manually annotated by BRENDA team
TBCA1, present as a single copy gene
SwissProt
Manually annotated by BRENDA team
Y-strain
-
-
Manually annotated by BRENDA team
acu1; acu2
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
deletion of ENA1 has no effect on the tolerance to potassium and rubidium. Mutant cells are unable to grow on media containing higher concentrations of sodium and lithium cations
metabolism
-
important regulatory role of Ang-(1-7) in the action of angiotensin II on the Na+-ATPase activity of proximal tubule cells by activation of MAS receptor. The MAS receptor plays an important role as a regulator of the effects mediated by AT1 receptor on proximal tubule sodium reabsorption and renal sodium excretion, overview
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
ATP + H2O + K+/in
ADP + phosphate + K+/out
show the reaction diagram
ATP + H2O + Li+/in
ADP + phosphate + Li+/out
show the reaction diagram
ATP + H2O + Na+/in
ADP + phosphate + Na+/out
show the reaction diagram
ATP + H2O + Na+/out
ADP + phosphate + Na+/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Rb+/in
ADP + phosphate + Rb+/out
show the reaction diagram
is transported as efficiently as K+
-
-
?
CTP + H2O
?
show the reaction diagram
-
-
-
?
GTP + H2O
?
show the reaction diagram
-
-
-
?
UTP + H2O
?
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADP + phosphate + Na+/out
ATP + H2O + Na+/in
show the reaction diagram
ATP + H2O + Na+/in
ADP + phosphate + Na+/out
show the reaction diagram
ATP + H2O + Na+/out
ADP + phosphate + Na+/in
show the reaction diagram
-
-
-
-
?
CTP + H2O
?
show the reaction diagram
-
-
-
?
GTP + H2O
?
show the reaction diagram
-
-
-
?
UTP + H2O
?
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ba2+
high affinity Na+ uptake is not inhibited by this cation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3beta,22alpha,25R)-26-(beta-D-glucopyranosyloxy)-2-methoxyfurost-5-en-3-yl O-D-apio-beta-D-furanosyl-(1-2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-4)]-beta-D-glucopyranoside
-
-
(3beta,22alpha,25R)-spirostan-3-yl O-D-apio-beta-D-furanosyl-(1-2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-4)]-beta-D-glucopyranoside
-
-
5-(N,N'-hexamethylene)-amiloride
-
-
5-(N-ethyl-N-isopropyl)-amiloride
-
-
7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole
-
-
adenosine
-
inhibits independently of the A3 receptor
angiotensin II
-
angiotensin II has an activating and regulatory role for Na+-ATPase activity in healthy rats, and angiotensin II links the enzyme activity to hypertension in spontaneously hypertensive rats, where it has an inhibitory effect on Na+-ATPase activity. The Ang II inhibitory effect is completely reversed by a specific antagonist of AT2 receptor, PD123319. Ang II interacts with different receptors in spontaneously hypertensive rats and WKY wild-type rats
ATPgammaS
-
-
atrial natriuretic peptide
-
selectively inhibits the enzyme in basolateral membranes of kidney proximal tubules by activation of guanylyl cyclase activity, which is inhibited by LY83583
-
Carbonyl cyanide m-chlorophenylhydrazone
ceramide
-
mediates enzyme inhibition to about 60% by activating protein kinase A and protein kinase Czeta, that regulate ion transporter activities. Inhibition of the kinase reverses the inhibitory effect of ceramide on Na+-ATPase
concanamycin A
-
-
Dicyclohexylcarbodiimide
diethylstilbestrol
-
-
Furosemide
Inosine
-
inhibits independently of the A3 receptor
losartan
-
prevents the increase in Na+-ATPase activity observed in 14-weekold spontaneously hypertensive rats
miltefosine
-
1-O-hexadecylphosphocholine
N,N'-dicyclohexylcarbodiimide
-
DCCD
N,N’-dicyclohexylcarbodiimide
-
78% residual activity at 1 mM in the presence of 10 mM NaCl. Inhibition in the absence of NaCl occurs after 20 min yielding 80 and 70% inhibition at pH 7.6 and pH 9.0, respectively
-
N-10-benzyl-amiloride
-
-
-
N-ethylmaleimide
nitrate
orthovanadate
Ouabain
prostaglandin E2
-
dose-dependent inhibition with maximal effect at 1 nM. The addition of 0.001 mM prostaglandin E2 decreases Na+-ATPase activity by 41%. The inhibitory effect of prostaglandin E2 on proximal tubule Na+-ATPase activity involves G protein and the activation of protein kinase A. The protein A-mediated inhibitory effect of prostaglandin E2 on Na+-ATPase activity requires previous activation of protein kinase C
Sodium azide
sodium orthovanadate
-
-
Tributyltin chloride
urodilatin
-
selectively inhibits the enzyme transiently in basolateral membranes of kidney proximal tubules by activation of guanylyl cyclase activity, which is inhibited by LY83583
-
valinomycin
-
-
vanadate
Venturicidin
[(dihydroindenyl)oxy]acetic acid
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
angiotensin II
ATP
-
ATPase activity increases as ATP increased and the activity is saturated at about 6 mM ATP
bile salt
-
induction of enzyme expression and increase in enzymic activity with concomitant decrease in intracellular ATP levels. In a bile salt-resistant mtant strain, tolerance of acidic pH-value is better than in parent strain. Expression and activity of enzyme are increased in the mutant
Ca2+
-
67% activity after addition of EGTA
carbonyl cyanide m-chlorophenyl hydrazine
-
-
carbonyl cyanide p-chlorophenylhydrazone
-
-
carbonyl cyanide p-trifluoromethoxyphenylhydrazone
-
-
gramicidin D
-
-
lysophosphatidic acid
-
stimulates the enzyme to 120% at 0.01 nM. Protein kinase C mediates the modulation of Na+-ATPase activity by lysophosphatidic acid
PacC transcription factor
required for efficient cation efflux at alkaline ambient pH
-
SO32-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.029 - 1.66
ATP
0.0005 - 0.0015
K+
pH 6.0, approximately
0.06
Li+/in
-
wild type enzyme, pH and temperature not specified in the publication
0.0005 - 56.7
Na+
0.02 - 2
Na+/in
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0
(3beta,22alpha,25R)-26-(beta-D-glucopyranosyloxy)-2-methoxyfurost-5-en-3-yl O-D-apio-beta-D-furanosyl-(1-2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-4)]-beta-D-glucopyranoside
Sus scrofa
-
obtained by extrapolation of half maximal inhibition
0
(3beta,22alpha,25R)-spirostan-3-yl O-D-apio-beta-D-furanosyl-(1-2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-4)]-beta-D-glucopyranoside
Sus scrofa
-
obtained by extrapolation of half maximal inhibition
0.0001
ceramide
Sus scrofa
-
pH 7.4, 37°C
0.22 - 0.5
Furosemide
0.044
miltefosine
Trypanosoma cruzi
-
-
0.0001
sodium orthovanadate
Leishmania amazonensis
-
-
0.0091
vanadate
Cavia porcellus
B3SI05
pH and temperature not specified in the publication
0.053 - 0.095
[(dihydroindenyl)oxy]acetic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000046
-
enzyme in isolated basolateral membranes of kidney proximal tubules, in presence of urodilatin or atrial natriuretic peptide, pH 7.0, temperature not specified in the publication
0.0000084
-
enzyme in isolated basolateral membranes of kidney proximal tubules, pH 7.0, temperature not specified in the publication
0.00325
-
ATPase activity in homogenate, hydrolysis of ATP, without ouabain, control
0.00336
-
ATPase activity in homogenate, hydrolysis of ATP, with 1 mM ouabain, control
0.00734
-
ATPase activity in homogenate, hydrolysis of ATP, with 1 mM ouabain, control, 10 mM MgCl2
0.00741
-
ATPase activity in homogenate, hydrolysis of ATP, without ouabain, control, 10 mM MgCl2
0.0076
-
Y895W mutant, 37ºC
0.00808
-
ATPase activity in homogenate, hydrolysis of ATP, with 1 mM ouabain, control, 10 mM MgCl2, 120 mM NaCl
0.00813
-
ATPase activity in homogenate, hydrolysis of ATP, without ouabain, control, 10 mM MgCl2, 120 mM NaCl
0.00818
-
ATPase activity in homogenate, hydrolysis of ATP, with 1 mM ouabain, control, 10 mM MgCl2, 120 mM NaCl, 30 mM KCl
0.00907
-
ATPase activity in homogenate, hydrolysis of ATP, without ouabain, control, 10 mM MgCl2, 120 mM NaCl, 30 mM KCl
0.0103
-
ATPase activity in plasma membranes in the presence of 1 mM ouabain, hydrolysis of ATP, control
0.01316
-
Y895C mutant, 37ºC
0.0133
-
Y895F mutant, 37ºC
0.0266
-
crude enzyme from membrane vesicles, at pH 7.6, temperature not specified in the publication
0.0272
-
ATPase activity in plasma membranes in the presence of 1 mM ouabain, hydrolysis of ATP, 10 mM MgCl2
0.0286
-
ATPase activity in plasma membranes in the presence of 1 mM ouabain, hydrolysis of ATP, 10 mM MgCl2, 120 mM NaCl, 30 mM KCl
0.0294
-
ATPase activity in plasma membranes in the presence of 1 mM ouabain, hydrolysis of ATP, 10 mM MgCl2, 120 mM NaCl
0.4667
-
after 17.5fold purification, at pH 7.6, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
the enzyme is strongly induced in the presence of Na+ at alkaline pH
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
high external pH enhances expression of the enzyme
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
ATPase activity assay
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.4
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
HUAEC cell, human umbilical cord endothelial cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
sub-pellicular region
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8000
-
1 * 69000 + 1 * 52000 + 1 * 38000 + 1 * 27000 + 1 * 24000 + 1 * 15000 + 1 * 14000 + 1 * 8000, SDS-PAGE
14000
-
1 * 69000 + 1 * 52000 + 1 * 38000 + 1 * 27000 + 1 * 24000 + 1 * 15000 + 1 * 14000 + 1 * 8000, SDS-PAGE
17000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
19000
-
1 * 57000 + 1 * 52000 + 1 * 35000 + 1 * 19000 + 1 * 15000 + 1 * 4800, SDS-PAGE
22000
-
x * 56000 + x * 52000 + x * 35000 + x * 25000 + x * 22000 + x * 16500 + x * 6500, SDS-PAGE
24000
-
1 * 69000 + 1 * 52000 + 1 * 38000 + 1 * 27000 + 1 * 24000 + 1 * 15000 + 1 * 14000 + 1 * 8000, SDS-PAGE
25000
-
x * 56000 + x * 52000 + x * 35000 + x * 25000 + x * 22000 + x * 16500 + x * 6500, SDS-PAGE
26000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
27000
-
1 * 69000 + 1 * 52000 + 1 * 38000 + 1 * 27000 + 1 * 24000 + 1 * 15000 + 1 * 14000 + 1 * 8000, SDS-PAGE
37000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
38000
-
1 * 69000 + 1 * 52000 + 1 * 38000 + 1 * 27000 + 1 * 24000 + 1 * 15000 + 1 * 14000 + 1 * 8000, SDS-PAGE
50000
1 * 90000 + 1 * 50000, SDS-PAGE
51000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
57000
-
1 * 57000 + 1 * 52000 + 1 * 35000 + 1 * 19000 + 1 * 15000 + 1 * 4800, SDS-PAGE
61000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
65000
-
3 * 65000 + 3 * 56000 + 1 * 29000
66000
-
1 * 66000 + 1 * 61000 + 1 * 51000 + 1 * 37000 + 1 * 26000 + 1 * 17000, SDS-PAGE
90000
1 * 90000 + 1 * 50000, SDS-PAGE
96664
-
x * 96664, calculated, x * 100000, SDS-PAGE
100000
-
x * 96664, calculated, x * 100000, SDS-PAGE
113000
calculated from amino acid sequence
115500
+AHw-predicted from cDNA sequence, 1047 amino acids+AHwAfA-
119700
calculation from sequence of cDNA
120000
calculated molecular mass, determined by SDS-PAGE and Western-blotting
123000
calculation from sequence of cDNA
123500
calculation from sequence of cDNA
150000
Western blot
400000
additional information
open reading frame of 3261 nucleotides encoding a predicted protein of 1087 amino acids
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
1 * 90000 + 1 * 50000, SDS-PAGE
hexamer
oligomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 11
-
when the pH is increased from pH 6.0 to pH 9.0, the enzyme activity is increased progressively. Increasing the pH further to pH 11.0 results in a slightly declined enzyme activity
719166
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
62%, 67.6% and 51.4% residual activity for wild-type, Y895F and YY895W mutant enzymes. Only 36.5% residual activity for Y895C mutant. The aromatic group contributes to thermal stability
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Glycerol
-
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, purified enzyme, 1 month, the enzyme remains stable
-
-80°C, 20 mM Tris-HCl, pH 7.6, 4 mM benzamidine
-
-80°C, n-dodecyl alpha-D-maltoside, 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
concanavalin A affinity column chromatography and Q-Sepharose column chromatography
native enzyme from kidney cortex and basolateral membranes from renal outer cortex
-
native enzyme from kidney cortex and basolateral membranes of proximal renal tubule cells
-
partially through preparation of basolateral membranes of kidney proximal tubules
-
PEG 6000 precipitation and Superose 6 gel filtration
-
plasma membrane vesicles are prepared
-
plasma membranes are isolated from the promastigotes of Leishmania amazonensis
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
+AHw-PCR products for the cytoplasmic-loop regions of the ATPase cloned into plasmid vectors and sequenced+AHwAfA-
expressed in Saccharomyces cerevisiae strain w303-1a
expression in Saccharomyces cerevisiae
expression in Saccharomyces cerevisiae ena1-4 nha1 mutant, sensitive to high K+ and Na+ concentrations
expression in Sacharomyces cerevisiae
into tht pCR II-TOPO vector, into the mammalian expression vector pEGFP-N1 for transfection of FreeStyle 293-F cells, and into the trypanosomatid shuttle vector pTREX for transformation of Trypanosoma cruzi epimastigotes
PCR products for the cytoplasmic-loop regions of the ATPase cloned into plasmid vectors and sequenced
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cells grown at 2 M NaCl show higher enzyme activity than those grown at 0.5 M NaCl. ATPase activity in is slightly increased upon increasing the pH from 5.0 to 7.6
-
isoform KPA2 transcript is down-regulated (0.2fold) in gametophytes during exposure to alkali stress (pH 9.5)
isoforms KPA1 transcript is up-regulated 2.3fold in gametophytes during exposure to alkali stress (pH 9.5). Transcription of isoform KPA1 in gametophytes is also induced by cold stress (15°C, 3.3fold increase of expression); transcription of isoform KPA2 in gametophytes is also induced by cold stress (15°C, 3.6fold increase of expression)
Na+-ATPase activity increases more than 2fold in the adult progeny of rats that are undernourished during lactation. Its physiological activation by angiotensin II is completely abolished
-
the Ena1 Na+-ATPase gene is highly upregulated by an increased osmotic pressure or sodium concentration (25fold increase of expression during the first 60 min of exposure to 1000 mM NaCl and then expression partly drops (12fold higher expression after 90 min))
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D893A
-
mutant with no significant Na+/K+ ATPase activity
D893E
-
mutant with no significant Na+/K+ ATPase activity
D893R
-
mutant with no significant Na+/K+ ATPase activity
G896I
-
mutant with no significant Na+/K+ ATPase activity
G896R
-
mutant with no significant Na+/K+ ATPase activity
S894D
-
mutant with similar Na+/K+ ATPase activity as the wild-type enzyme
S894I
-
mutant with similar Na+/K+ ATPase activity as the wild-type enzyme
Y895C
-
mutant with similar Na+/K+ ATPase activity as the wild-type enzyme
Y895F
-
mutant with similar Na+/K+ ATPase activity as the wild-type enzyme
Y895W
-
mutant with significantly reduced Na+/K+ ATPase activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
expression of triple hemagglutinin-tagged enzyme in Nicotiana tabacum confers increased NaCl and LiCl tolerance to cells. Under moderate slat stress, enzyme expression results in accumulation of less Na+, Li+ and K+ than in wild-type
medicine
pharmacology