Information on EC 7.6.2.1 - phospholipid-translocating ATPase and Organism(s) Homo sapiens

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Homo sapiens


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
7.6.2.1
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RECOMMENDED NAME
GeneOntology No.
phospholipid-translocating ATPase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + phospholipid [side 1] = ADP + phosphate + phospholipid [side 2]
show the reaction diagram
P-type ATPase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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-
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transmembrane transport
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, phospholipid-flipping)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme moves phospholipids such as phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine from one membrane face to the other ('flippase').
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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P4-ATPase deficiencies are linked to liver disease, obesity, diabetes, hearing loss, neurological deficits, immune deficiency, and reduced fertility
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl phosphate + H2O
acetate + phosphate
show the reaction diagram
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translocation of phosphatidylserine from the outer to the inner leaflet of resealed erythrocyte ghosts
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
ATP + H2O + 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-sn-glycero-3-phospho-L-serine/in
ADP + phosphate + 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-sn-glycero-3-phospho-L-serine/out
show the reaction diagram
-
-
-
?
ATP + H2O + 7-nitrobenz-2-oxa-1,3-diazol-4-yl-phosphatidylserine/in
ADP + phosphate + 7-nitrobenz-2-oxa-1,3-diazol-4-yl-phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + asolectin/out
ADP + phosphate + asolectin/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + carboxyfluoresceinyl-phosphatidylserine/in
ADP + phosphate + carboxyfluoresceinyl-phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + coumaryl-phosphatidylserine/in
ADP + phosphate + coumaryl-phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + galactocerebroside/out
ADP + phosphate + galactocerebroside/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + lactocerebroside/out
ADP + phosphate + lactocerebroside/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + N-methyl-dilauroylphosphatidyl-DL-serine/out
ADP + phosphate + N-methyl-dilauroylphosphatidyl-DL-serine/in
show the reaction diagram
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rapid change of cell morphology from echinocyte to stomatocyte
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-
?
ATP + H2O + phosphatidylcholine/in
ADP + phosphate + phosphatidylcholine/out
show the reaction diagram
ATP + H2O + phosphatidylcholine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
ATP + H2O + phosphoethanolamine/in
ADP + phosphate + phosphoethanolamine/out
show the reaction diagram
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low activity
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-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
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-
-
?
ATP + H2O + rhodamine 123/out
ADP + phosphate + rhodamine 123/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + sn-1,2-dilauroylphosphatidyl-D-serine/out
ADP + phosphate + sn-1,2-dilauroylphosphatidyl-D-serine/in
show the reaction diagram
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rapid change of cell morphology from echinocyte to stomatocyte
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-
?
ATP + H2O + sn-1,2-dilauroylphosphatidyl-L-serine/out
ADP + phosphate + sn-1,2-dilauroylphosphatidyl-L-serine/in
show the reaction diagram
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rapid change of cell morphology from echinocyte to stomatocyte
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-
?
ATP + H2O + sn-2,3-dilauroylphosphatidyl-L-serine/out
ADP + phosphate + sn-2,3-dilauroylphosphatidyl-L-serine/in
show the reaction diagram
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low activity, slow change of cell morphology from echinocyte to stomatocyte
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-
?
ATP + H2O + sphingomyelin/out
ADP + phosphate + sphingomyelin/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + verapamil/out
ADP + phosphate + verapamil/in
show the reaction diagram
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highest activity
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-
?
dATP + H2O
dADP + H2O
show the reaction diagram
GTP + H2O
GDP + phosphate
show the reaction diagram
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at 2 mM, 40% of the activity with 2 mM ATP
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-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
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translocation of phosphatidylserine from the outer to the inner leaflet of resealed erythrocyte ghosts
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?
additional information
?
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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
ATP + H2O
ADP + phosphate
show the reaction diagram
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
ATP + H2O + phosphoethanolamine/in
ADP + phosphate + phosphoethanolamine/out
show the reaction diagram
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low activity
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?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Q9NTI2
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-
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-monoolein
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0.5 mM significantly reduce the P-glycoprotein protein expression, 0.1 mM of 1-monoolein does not have any significant effect on the expression of P-glycoprotein
1-monostearin
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0.5 mM significantly reduce the P-glycoprotein protein expression, 0.1 mM of 1-monostearin does not have any significant effect on the expression of P-glycoprotein
azide
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Cd2+
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Diamide
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DTNB
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elaiophylin
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partial inhibition of Mg+-ATPase activity, translocation of phosphatidylserine is almost completely abolished
eosin Y
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almost complete inhibition of both Mg2+-ATPase activity and translocation
orthovanadate
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pyridyldithioethylamine
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suramin
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competitive inhibitor of ATP towards both Mg2+-ATPase activity and aminophospholipid translocation. Inhibition of translocation occurs at higher inhibitor concentration than the inhibition of Mg2+-ATPase activity
vanadate
vanadyl ion
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inhibits the enzyme from the extracellular surface
verapamil
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complete inhibition at 0.05 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-aminonaphthalene-8-sulfonate
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stimulates
1-heptanesulfonate
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stimulates
2,4-dinitrophenol
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stimulates, stimulation is prevented by 0.2-1.0 mM Ca2+
4-Aminosalicylate
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stimulates
ATP
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biphasic activation, K0.5 = 0.02 mM and 0.4 mM
Benzoate
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stimulates
Brij
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stimulates
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CDC50 proteins
CDC50A and CDC50B, cloning and expression of the abut 60 kDa proteins, required for full translocase activity, 2.5-5fold activition, proteins are pivotal factors in the trafficking of ATP8B1 to the plasma membrane and thus may be essential determinants of ATP8B1-related disease, physical interacion with ATP8B1, overview
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CDC50A
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cholate
dithiothreitol
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partially stimulates
glycerophosphoserine
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prevents transport of phosphatidylserine
glycocholate
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slightly increases the efflux of phospholipids and cholesterol from cells
p-hydroxyphenylacetate
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stimulates
p-nitrophenol
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stimulates
phenylacylbromide
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Phenylglyoxal
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salicylate
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stimulates
SDS
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stimulates
sulfanilamide
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stimulates
Sulfanilic acid
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stimulates
taurocholate
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increases the efflux of phospholipids and cholesterol from cells, the taurocholate monomer plays an important role in ABCB4-mediated lipid secretion
Tetradecyltrimethylammonium bromide
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stimulates
thrombin
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induces platelet phosphatidylserine exposure, inhibited by c7E3 or SR121566
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Triton X-100
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stimulates
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.03 - 1.31
acetyl phosphate
0.211 - 0.704
ATP
1.17 - 1.46
p-nitrophenyl phosphate
additional information
additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45 - 55
purified lipid-stimulated enzyme, pH 7.5, 37°C
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
flippase assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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below 4°C transport of phospholipids is inhibited in both erythrocytes and fibroblasts, warming to 7°C activates transport in fibroblasts
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the predominant P4 ATPases in pure pancreatic beta cells and pancreatic islets are ATP8B1, ATP8B2, and ATP9A; the predominant P4 ATPases in pure pancreatic beta cells and pancreatic islets are ATP8B1, ATP8B2, and ATP9A. ATP9A is concentrated in plasma membrane; the predominant P4 ATPases in pure pancreatic beta cells and pancreatic islets are ATP8B1, ATP8B2, and ATP9A. Isoform ATP8B1 is highly concentrated in insulin secretory granules
Manually annotated by BRENDA team
disc membranes
Manually annotated by BRENDA team
outer segment disc membranes of rod and cone photoreceptor cells, high expression of atp8a2
Manually annotated by BRENDA team
high expression of atp8a2
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
ATP8B1 in absence of CDC50A and CDC50
Manually annotated by BRENDA team
additional information
localization study by immunofluorescence microscopy
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
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x * 110000, SDS-PAGE
132000
x * 132000, about, recombinant enzyme, SDS-PAGE
140000
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x * 140000, recombinant ABCB4, SDS-PAGE
170000
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SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterodimer
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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analysis of glycosylation of ABCB4, cleavage by endoglycosidase H or peptide N-glycosidase F, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme is very instable and rapidly degenerated during purification
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 35 days, stored erythrocytes show pH-dependently reduced flippase activity and ATP depletion, upon ATP supply the activity can be restored, overview
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
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partially from erythrocytes
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recombinant enzyme from HEK-293 cells by immunoaffinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP10C
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gene atp8a2, DNA and amino acid sequence determination and analysis, expression in HEK-293 cells
isolated stable expression of N-terminally GFP-tagged ATP8B1 in UPS-1 cells, a nonpolarized CHO-K1 mutant cell line with a defect in the nonendocytic uptake of the NBD-PS analogue, by lentiviral transduction leading to protein localization in the endoplasmic reticulum, co-expression with N-terminally HA-tagged CDC50 proteins results in relocalization of ATP8B1 from the endoplasmic reticulum to the plasma membrane, natural phosphatidylserine exposure in the outer leaflet of the plasma membrane was reduced by 17%-25% in cells coexpressing ATP8B1 and CDC50 proteins in comparison with cells expressing ATP8B1 alone, coexpression of ATP8B1 and CDC50A in WIF-B9 cells resulted in colocalization of both proteins in the canalicular membrane, overview
stable expression of ABCB4 in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
coexpression of CDC50A increased the total cellular expression level of flippase ATP8A1
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I376M
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missense mutation identified in a patient with cerebellar ataxia, mental retardation and dysequilibrium syndrome. The mutation lies in a highly conserved C-terminal transmembrane region of E1 E2 ATPase domain
K1075M
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site-directed mutagenesis in the Walker A motif results in an inactive mutant
K435M
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site-directed mutagenesis in the Walker A motif results in an inactive mutant
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing isoforms ATP8B1, ATP8B2, ATP11A, and ATP11C; assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing isoforms ATP8B1, ATP8B2, ATP11A, and ATP11C; assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing isoforms ATP8B1, ATP8B2, ATP11A, and ATP11C; assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing isoforms ATP8B1, ATP8B2, ATP11A, and ATP11C
medicine