Information on EC 3.6.3.1 - phospholipid-translocating ATPase

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

EC NUMBER
COMMENTARY
3.6.3.1
-
RECOMMENDED NAME
GeneOntology No.
phospholipid-translocating ATPase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + phospholipid [side 1] = ADP + phosphate + phospholipid [side 2]
show the reaction diagram
P-type ATPase
-
ATP + H2O + phospholipid [side 1] = ADP + phosphate + phospholipid [side 2]
show the reaction diagram
P-type ATPase
Q29449
ATP + H2O + phospholipid [side 1] = ADP + phosphate + phospholipid [side 2]
show the reaction diagram
The Cdc50p/Lem3p family comprises a set of subunits specific to phospholipid-translocating P-type ATPases. Cdc50p physically associates with Drs2p. Cds50p forms a complex with Drs2p, whereas Lem3p forms a complex with Dnf1p in vivo. The Cdc50p-Drs2p complex possesses aminophospholipid translocase activity, which translocates aminophospholipids more efficiently than phosphatidylcholine.
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (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').
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aminophospholipid flippase
-
-
-
-
aminophospholipid flippase 10
-
-
-
-
aminophospholipid flippase 11
-
-
-
-
aminophospholipid flippase 12
-
-
-
-
aminophospholipid translocase
-
-
-
-
aminophospholipid translocase VC
-
-
-
-
ATPase II
-
-
-
-
ATPVC
-
-
-
-
ATPVD
-
-
-
-
flippase
-
-
-
-
HUSSY-20
-
-
-
-
Mg2+-ATPase
-
-
-
-
Mg2+-ATPase A
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
4 isoforms of ATPase II
Uniprot
Manually annotated by BRENDA team
gene atp8a2
UniProt
Manually annotated by BRENDA team
gene atp8a2
UniProt
Manually annotated by BRENDA team
mRNA of ATP8B1; isozyme ATP8B1
UniProt
Manually annotated by BRENDA team
multidrug resistance chinese hamster
-
-
Manually annotated by BRENDA team
C57/B6 and BALB/c mice, gene atp8a2
UniProt
Manually annotated by BRENDA team
C57BL/6 mice, two isozymes Atp8a1 and flippase
-
-
Manually annotated by BRENDA team
diverse strains, overview
-
-
Manually annotated by BRENDA team
five P-type ATPases involved inlipid transport
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-
Manually annotated by BRENDA team
several strains, genes DRS2, DNF1 and DNF2, and DNF3
-
-
Manually annotated by BRENDA team
strain CCY2811, gene swa4
-
-
Manually annotated by BRENDA team
strain EHY227
-
-
Manually annotated by BRENDA team
strain LMY65, LMY67, LMY69, and LMY94
-
-
Manually annotated by BRENDA team
strain sec61
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae CCY2811
strain CCY2811, gene swa4
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae EHY227
strain EHY227
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae LMY65
strain LMY65, LMY67, LMY69, and LMY94
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae sec61
strain sec61
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
knockdown of ALA1 expression causes a cold-sensitive growth defect in plants
malfunction
-
P4-ATPase deficiencies are linked to liver disease, obesity, diabetes, hearing loss, neurological deficits, immune deficiency, and reduced fertility
physiological function
-
flippase selectively transports phosphatidylserine from the outer to the inner plasma membrane layer and thereby maintains transbilayer phospholipid asymmetry. Possible role for Rho 34 and downstream effector Rho-associated kinase in the process of reversible phosphatidylserine exposure, involving the flippase and apoptosis in cardiomyocytes. Regulation of Rho-ROCK signaling and effect of inhibition of Rho-ROCK signaling on flippase activity, overview. Inhibition of Rho-ROCK signaling, by Y27632 or H1152, induces apoptotic and non-apoptotic phosphatidylserine exposure in cardiomyocytes via inhibition of flippase
physiological function
P98200
P4-ATPases in general are implicated in the energy-dependent translocation of aminophospholipids across cell membranes. Atp8a2 is implicated in the generation and maintenance of phosphatidylserine asymmetry in photoreceptor disc membranes
physiological function
Q9NTI2
P4-ATPases in general are implicated in the energy-dependent translocation of aminophospholipids across cell membranes. Atp8a2 is implicated in the generation and maintenance of phosphatidylserine asymmetry in photoreceptor disc membranes
physiological function
C7EXK4
P4-ATPases in general are implicated in the energy-dependent translocation of aminophospholipids across cell membranes. Atp8a2 is implicated in the generation and maintenance of phosphatidylserine asymmetry in photoreceptor disc membranes
physiological function
-
the enzyme flips phospholipid across the bilayer to create an asymmetric membrane structure with substrate phospholipids, such as phosphatidylserine and phosphatidylethanolamine, enriched within the cytosolic leaflet. Fippase helps to form transport vesicles that bud from Golgi and endosomal membranes
physiological function
-
the enzyme flips phospholipid across the bilayer to create an asymmetric membrane structure with substrate phospholipids, such as phosphatidylserine and phosphatidylethanolamine, enriched within the cytosolic leaflet. Fippase helps to form transport vesicles that bud from Golgi and endosomal membranes
physiological function
-
the enzyme flips phospholipid across the bilayer to create an asymmetric membrane structure with substrate phospholipids, such as phosphatidylserine and phosphatidylethanolamine, enriched within the cytosolic leaflet. Flippase helps to form transport vesicles that bud from Golgi and endosomal membranes
physiological function
-
the enzyme flips phospholipid across the bilayer to create an asymmetric membrane structure with substrate phospholipids, such as phosphatidylserine and phosphatidylethanolamine, enriched within the cytosolic leaflet. Flippase helps to form transport vesicles that bud from Golgi and endosomal membranes
physiological function
-
the enzyme translocates phospholipids from the exoplasmic (lumenal) to the cytoplasmic leaflet of lipid bilayers
physiological function
Q9QZW0
the P4-type ATPase ATP11C is redundant during B cell development in the fetal liver, yet essential in the context of adult bone marrow, where it is required for optimal responses to interleukin-7 and sustained expression of Ebf1
physiological function
-
type IV P-type ATPases catalyzes translocation of phospholipid across a membrane to establish an asymmetric bilayer structure with phosphatidylserine and phosphatidylethanolamine restricted to the cytosolic leaflet
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl phosphate + H2O
acetate + phosphate
show the reaction diagram
-
translocation of phosphatidylserine from the outer to the inner leaflet of resealed erythrocyte ghosts
-
-
?
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
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
ADP + phosphate
show the reaction diagram
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the stoichiometry between lipid translocation and ATP consumption is 1.13 for phosphatidylserine and 1.11 for phosphatidylethanolamine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
translocation of the aminophospholipids, phosphatidylserine and phosphatidylethanolamine, from the outer leaflet to the inner leaflet of the lipid bilayer, enzyme is involved in ATP-dependent erythrocyte shape change
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of ethanolamine at a rate 10fold slower than phosphatidylserine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
selectively pumps the aminophospholipids phospatidylserine and phosphatidylethanolamine from the outer to the inner monolayer of eukaryotic cells and is predominantly responsible for the asymmetric phospholipid distribution of the plasma membrane
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
selectively pumps the aminophospholipids phospatidylserine and phosphatidylethanolamine from the outer to the inner monolayer of eukaryotic cells and is predominantly responsible for the asymmetric phospholipid distribution of the plasma membrane
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
selectively pumps the aminophospholipids phospatidylserine and phosphatidylethanolamine from the outer to the inner monolayer of eukaryotic cells and is predominantly responsible for the asymmetric phospholipid distribution of the plasma membrane
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of phosphatidylserine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of phosphatidylserine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of phosphatidylserine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
Q29449
phosphatidylserine is essential for the dephosphorylation of the phosphoenzyme intermediate
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the protein serves primarily to prevent the accumulation of phosphatidylserine on the outer surface of the cell
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of a spin-labeled phosphatidylserine analogue from the inner to the outer membrane leaflet provided Mg2+-ATP is present. The ATP-dependent transport of the phosphatidylethanolamine analogue requires the presence of an anionic phospholipid, e.g. phosphatidylinositol in the outer leaflet
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
translocation of phosphatidylserine from the outer to the inner leaflet of resealed erythrocyte ghosts
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
activity is stimulated twofold by addition of 2 mM ATP
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
ATPase activity is stimulated by phosphatidylserine but not by phosphatidylcholine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of N-methylphosphatidylserine
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?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
transport of phosphatidylethanolamine
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
a decrease in the size of the pool of flippase transportable phosphatidylethanolamine molecules causes a corresponding decrease in Mg2+-ATPase activity
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
down-regulation of the aminophospholipid translocase activity is an early step in the programmed cell death in lymphocytes, a step that contributes to the appearance of phosphatidylserine on the cell surface as a recognition signal for phagocytosis
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
Q29449
the enzyme plays an important role in the maintenance of membrane phospholipid asymmetry, observed in plasma membrane and membranes of certain cellular organelles
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the initial maintenance of phospholipid asymmetry in diamide-treated erythrocytes can be solely ascribed to the action of the ATP-dependent aminophospholipid translocase
-
-
-
ATP + H2O
ADP + phosphate
show the reaction diagram
-
role in aminophospholipid transport
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
role of the enzyme in the control of erythrocyte shape, possibly through association with the ATP-dependent translocation of phosphatidylserine and phosphatidylethanolamine from the outer to the inner leaflet of the bilayer
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
Q29449
phosphatidylserine is essential for the dephosphorylation of the phosphoenzyme intermediate. Without phosphatidylserine, ATPase II accumulates as phosphoenzyme in the presence of ATP, resulting in the interruption of its catalytic cycle
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the enzyme is responsible for the inward transport of phosphatidylserine and phosphatidylethanolamine within the erythrocyte membrane
-
-
?
ATP + H2O + 1-palmitoyl-2-(6-(7-nitro-2-1,3-benzoxadiazole)-aminocaproyl)-phosphatidylcholine/out
ADP + phosphate + 1-palmitoyl-2-(6-(7-nitro-2-1,3-benzoxadiazole)-aminocaproyl)-phosphatidylcholine/in
show the reaction diagram
-
internalization through the plasma membrane by the Dnf1p-Lem3p complex
-
-
?
ATP + H2O + 1-palmitoyl-2-(6-(7-nitro-2-1,3-benzoxadiazole)-aminocaproyl)-phosphatidylethanolamine/out
ADP + phosphate + 1-palmitoyl-2-(6-(7-nitro-2-1,3-benzoxadiazole)-aminocaproyl)-phosphatidylethanolamine/in
show the reaction diagram
-
internalization through the plasma membrane by the Dnf1p-Lem3p complex
-
-
?
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
O43520
-
-
-
?
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 + cholera toxin/in
ADP + phosphate + cholera toxin/out
show the reaction diagram
-
through ATP hydrolysis and an interaction with the cytoplasmic membrane protein EpsL, EpsE supports secretion of cholera toxin across the outer membrane
-
-
?
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 + H33342/out
ADP + phosphate + H33342/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + lactocerebroside/out
ADP + phosphate + lactocerebroside/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + Lipid A/in
ADP + phosphate + Lipid A/out
show the reaction diagram
P60752
-
-
-
?
ATP + H2O + lysophosphatidylcholine/out
ADP + phosphate + lysophosphatidylcholine/in
show the reaction diagram
-
lysophosphatidylcholine is a bona fide biological substrate transported by the yeast plasma membrane ATPases, Dnf1p and Dnf2p, in consort with a second protein Lem3p
-
-
?
ATP + H2O + lysophosphatidylethanolamine/out
ADP + phosphate + lysophosphatidylethanolamine/in
show the reaction diagram
-
lysophosphatidylethanolamine is a bona fide biological substrate transported by the yeast plasma membrane ATPases, Dnf1p and Dnf2p, in consort with a second protein Lem3p
-
-
?
ATP + H2O + miltefosine/in
ADP + phosphate + miltefosine/out
show the reaction diagram
-
LdMT and LdRos3 form part of the same translocation machinery that determines flippase activity and miltefosine sensitivity in Leishmania
-
-
?
ATP + H2O + N-methyl-dilauroylphosphatidyl-DL-serine/out
ADP + phosphate + N-methyl-dilauroylphosphatidyl-DL-serine/in
show the reaction diagram
-
rapid change of cell morphology from echinocyte to stomatocyte
-
-
?
ATP + H2O + phosphatidylcholine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
-
palmitoyl-(NBD-hexanoyl)-PC , selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylcholine/in
ADP + phosphate + phosphatidylcholine/out
show the reaction diagram
-
preferred substrate of Dnf1
-
-
?
ATP + H2O + phosphatidylcholine/out
ADP + phosphate + phosphatidylcholine/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
P32660, P39524, Q12674
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
C7EXK4
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
G5EBH1, O18182, P91203, Q75PE3, Q7YXV5
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
P60752
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
-
selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry, palmitoyl-(NBD-hexanoyl)-PE , selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
C7EXK4
the enzyme is specific for ATP and shows no activity with GTP, AMP-PNP, GDP, or ADP
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
Saccharomyces cerevisiae EHY227
-
selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry, palmitoyl-(NBD-hexanoyl)-PE , selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
low activity, transport from the outer to the inner leaflet of the plasma membrane, the activity is regulated by Fas-, caspase 8-, and caspase 3-dependent signaling in erythrocytes with differences in old and young red blood cells, overview
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
transport from the exoplasmic to the cytosolic leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
transport from the luminal leaflet of the membrane to the cytosolic leaflet, 7-nitro-2-1,3-benzoxadiazol-4-yl-fluorescent-labeled substrate, transport from the luminal leaflet of the membrane to the cytosolic leaflet
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
low activity, transport from the outer to the inner leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
P32660, P39524, Q12674
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
C7EXK4
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
G5EBH1, O18182, P91203, Q75PE3, Q7YXV5
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane to maintain lipid asymmetry in the plasma membrane and secretory vesicles
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane, exposure of PS on the surface of cells serves as a binding site for haemostatic factors, triggers cell-cell interaction and recognition by macrophages and phospholipases. Exposure of PS on the red cell surface plays a significant role in sickle cell pathology
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the membrane
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane of erythrocytes to maintainthe lipid asymmetry, overview
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
O43520
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane, proteins are pivotal factors in the trafficking of ATP8B1 to the plasma membrane and thus may be essential determinants of ATP8B1-related disease
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport/flip of phosphatidylserine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
ABCB4 is required for ATP-dependent phosphatidylcholine secretion into the bile and to translocate phosphatidylcholine across the plasma membrane, overview
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
palmitoyl-(NBD-hexanoyl)-PS , selective ATP-dependent transport/flip of phosphatidylserine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
O43520
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
leading to reversible exposure on in the outer plasma membrane leaflet on the cell surface of cardiomyocytes by a flip-flop mechanism
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
C7EXK4
the enzyme is specific for ATP and shows no activity with GTP, AMP-PNP, GDP, or ADP
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
preferred substrate of Drs2
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
Saccharomyces cerevisiae EHY227
-
selective ATP-dependent transport/flip of phosphatidylserine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
Q148W0
-
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
flippase activity: transport from the outer to the inner leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the exoplasmic to the cytosolic leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the external leaflet of the membrane to the inner leaflet, the enzyme controls the level of phosphatidylserine exposed to the platelet surface antagonizing to the scramblase activity, overview
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the luminal leaflet of the membrane to the cytosolic leaflet
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the outer to the inner leaflet of the plasma membrane, the activity is regulated by Fas-, caspase 8-, and caspase 3-dependent signaling in erythrocytes with differences in old and young red blood cells, overview
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
7-nitro-2-1,3-benzoxadiazol-4-yl-fluorescent-labeled substrate, transport from the external leaflet of the membrane to the inner leaflet
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
7-nitro-2-1,3-benzoxadiazol-4-yl-fluorescent-labeled substrate, transport from the luminal leaflet of the membrane to the cytosolic leaflet
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the exoplasmic to the cytosolic leaflet of the plasma membrane, and from the lumenal side of granules to the external side
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the outer to the inner leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphoethanolamine/in
ADP + phosphate + phosphoethanolamine/out
show the reaction diagram
-
low activity
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
-
-
-
ir
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
P98200
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Q9NTI2
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
Dnf1p and Dnf2p are necessary for the internalization phospholipids across the plasma membrane of Saccharomyces cerevisiae, overview. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
LdMT Is required but not sufficient for the inward-directed translocation activity of phospholipids and miltefosine across the plasma membrane, LdRos3 is additionally required
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
P4-ATPases Drs2p and Dnf1p cycle between the exocytic and endocytic pathways, and maintain a steady-state localization to internal organelles requiring endocytosis signals, Drs2p is an essential endocytic cargo in cells compromised for Ub-dependent endocytosis
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
phospholipid translocases are involved in the generation of phospholipid asymmetry in membrane bilayers
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
the enzyme is involved in protein trafficking, Drs2p acts in complex with the allelic CDC50 protein in ATP-dependent phosphatidylserine translocation playing a role in restricting the substrate to the cytosolic leaflet of the Golgi and the plasma membrane, overview
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
transbilayer movement of phospholipids in an unidirectional fashion in biological membranes is mediated by energy-dependent and energy-independent flippases
-
-
ir
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
ATP-dependent transport of phospholipids from outer to the inner monolayer of the cell membrane to maintain lipid asymmetry, the C-terminal and N-terminal NPFXD motifs ar functionally required by Drs2p and Drf1p, respectively, overview
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
ATP-dependent transport of phospholipids from outer to the inner monolayer of the cell membrane to maintain lipid asymmetry, usage of fluorescent labeled 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled, NBD-labeled, phospholipid substrate. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae LMY65
-
Dnf1p and Dnf2p are necessary for the internalization phospholipids across the plasma membrane of Saccharomyces cerevisiae, overview. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast, ATP-dependent transport of phospholipids from outer to the inner monolayer of the cell membrane to maintain lipid asymmetry, usage of fluorescent labeled 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled, NBD-labeled, phospholipid substrate. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae sec61
-
transbilayer movement of phospholipids in an unidirectional fashion in biological membranes is mediated by energy-dependent and energy-independent flippases
-
-
ir
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae CCY2811
-
the enzyme is involved in protein trafficking, Drs2p acts in complex with the allelic CDC50 protein in ATP-dependent phosphatidylserine translocation playing a role in restricting the substrate to the cytosolic leaflet of the Golgi and the plasma membrane, overview
-
-
?
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
-
rapid change of cell morphology from echinocyte to stomatocyte
-
-
?
ATP + H2O + sn-1,2-dilauroylphosphatidyl-L-serine/out
ADP + phosphate + sn-1,2-dilauroylphosphatidyl-L-serine/in
show the reaction diagram
-
rapid change of cell morphology from echinocyte to stomatocyte
-
-
?
ATP + H2O + sn-2,3-dilauroylphosphatidyl-L-serine/out
ADP + phosphate + sn-2,3-dilauroylphosphatidyl-L-serine/in
show the reaction diagram
-
low activity, slow change of cell morphology from echinocyte to stomatocyte
-
-
?
ATP + H2O + sphingomyelin/out
ADP + phosphate + sphingomyelin/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + tetramethylrosamine/out
ADP + phosphate + tetramethylrosamine/in
show the reaction diagram
-
-
-
-
?
ATP + H2O + verapamil/out
ADP + phosphate + verapamil/in
show the reaction diagram
-
highest activity
-
-
?
dATP + H2O
dADP + H2O
show the reaction diagram
-
-
-
-
?
dATP + H2O
dADP + H2O
show the reaction diagram
-
at 2 mM nearly as active as ATP
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
show the reaction diagram
-
translocation of phosphatidylserine from the outer to the inner leaflet of resealed erythrocyte ghosts
-
-
?
GTP + H2O
GDP + phosphate
show the reaction diagram
-
at 2 mM, 40% of the activity with 2 mM ATP
-
-
?
additional information
?
-
-
flippase recognizes multiple structural elements in its preferred lipid substrate. The lipid structural elements include a primary amine group, limited headgroup size and and sn-1,2-glycerol backbone. The presence of carboxyl group accelerates transport, but is not required for activity
-
-
-
additional information
?
-
-
the enzyme is directly involved in miltefosine uptake in eukaryotic cells
-
-
-
additional information
?
-
-
The enzyme is essential for inward translocation of NBD-labeled phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine across the plasmamembrane.
-
-
-
additional information
?
-
-
the lipid flippase activity of enzyme is associated with its drug transport function
-
-
-
additional information
?
-
-
the membrane lipid bilayer asymmetry is maintained by the enzyme
-
-
-
additional information
?
-
-
the enzyme is able to promote the translocalisation of aminophospholipids and glycerophosphocholine molecules such as NBD-phosphatidylcholine and edelfosine and non glycerol based alkylphosphocholine miltefosin
-
-
-
additional information
?
-
-
the enzyme translocates phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin
-
-
-
additional information
?
-
-
the enzyme is a P-type ATPase involved in regulation of the lipid asymmetry of the cell membrane
-
-
-
additional information
?
-
-
the enzyme is a P-type ATPase involved in regulation of the lipid asymmetry of the cell membrane, especially Neo1p is important, Drs2p is involved in vesicle formation in the Golgi and thus influences the plasma membrane distribution of aminophospholipids despite its localization the Golgi membrane, mechanism
-
-
-
additional information
?
-
-
the Lem3p-Dnf1p complex can substitute for the Cdc50p-Drs2p complex, its redundant partner in the endosomal/trans-Golgi network compartments, Dnf1p forms a complex with Lem3p acting as aminophospholipid translocase
-
-
-
additional information
?
-
-
the enzyme depends on ATP
-
-
-
additional information
?
-
-
the enzyme depends on ATP
-
-
-
additional information
?
-
-
endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway, overview. The homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively, these putative heteromeric PLTs share an essential function for cell growth, overview
-
-
-
additional information
?
-
-
functional co-dependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the trans-Golgi network and early endosomes of Saccharomyces cerevisiae, Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function, Drs2p physically interacts with AP-1, overview
-
-
-
additional information
?
-
-
glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity, regulation and physiological effects, overview
-
-
-
additional information
?
-
-
loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, overview
-
-
-
additional information
?
-
-
Cdc50 family proteins form complexes with Drs2 family proteins, overview
-
-
-
additional information
?
-
-
complex formation of Drs2p with CDC50, overview
-
-
-
additional information
?
-
-
no transport of (NBD-hexanoyl)-sphingosine-1-phosphocholine
-
-
-
additional information
?
-
O43520
recombinant ATP8B1 Physically Interacts with HA-CDC50A and HA-CDC50B, uptake of 7-nitro-2-1,3-benzoxadiazol-4-yllabeled phosphatidylcholine, phosphatidylethanolamine and sphingomyelin is not dependent on ATP8B1-CDC50 expression
-
-
-
additional information
?
-
-
shape change of giant unilamellar vesicles can be used as a tool to study the occurrence and time scale of flippase-mediated transbilayer movement of unlabeled phospholipids, overview
-
-
-
additional information
?
-
-
substrate specificity, overview, no transport of dilauroylphosphatidylcholine, poor activity with dilauroylphosphatidylhydroxypropionate, dilauroylphosphatidylhomoserine, dilauroylphosphatidylserine-methyl ester, or sn-2,3-dilauroylphosphatidyl-D-serine
-
-
-
additional information
?
-
Q6UQ17
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
-
additional information
?
-
-
isozyme Drs2p interacts with the guanine nucleotide exchange factor Gea2p involved in activation of ADP-ribosylation factors, isozyme Neo1p interacts with the guanine nucleotide exchange factor Ysl2p/Mon2p and the Arf Arl1p, and cooperation between these three proteins is important for recruitment of clathrin adaptors
-
-
-
additional information
?
-
-
phosphatidylcholine, phosphatidylethanolamine, phophatidylserine, triglyceride, and cholesterol are no substrates of P-glycoprotein, ethyl acetate extracts from mouse brain homogenate exhibit weak substrate activity of P-glycoprotein
-
-
-
additional information
?
-
P98200
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
Q9NTI2
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
C7EXK4
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
Q9NTI2
dithionite NBD-lipid assay for detection of flippase activity
-
-
-
additional information
?
-
C7EXK4
dithionite NBD-lipid assay for detection of flippase activity
-
-
-
additional information
?
-
-
the enzyme does not translocalize 7-nitrobenz-2-oxa-1,3-diazol-4-yl-phosphatidylcholine or coumaryl-phosphatidylcholine
-
-
-
additional information
?
-
-
wild type Dnf1 cannot translocate NBD-SM or NBD-PA
-
-
-
additional information
?
-
Saccharomyces cerevisiae EHY227
-
loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, overview, no transport of (NBD-hexanoyl)-sphingosine-1-phosphocholine
-
-
-
additional information
?
-
Saccharomyces cerevisiae sec61
-
shape change of giant unilamellar vesicles can be used as a tool to study the occurrence and time scale of flippase-mediated transbilayer movement of unlabeled phospholipids, overview
-
-
-
additional information
?
-
Saccharomyces cerevisiae CCY2811
-
complex formation of Drs2p with CDC50, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
selectively pumps the aminophospholipids phospatidylserine and phosphatidylethanolamine from the outer to the inner monolayer of eukaryotic cells and is predominantly responsible for the asymmetric phospholipid distribution of the plasma membrane
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
down-regulation of the aminophospholipid translocase activity is an early step in the programmed cell death in lymphocytes, a step that contributes to the appearance of phosphatidylserine on the cell surface as a recognition signal for phagocytosis
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
Q29449
the enzyme plays an important role in the maintenance of membrane phospholipid asymmetry, observed in plasma membrane and membranes of certain cellular organelles
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the initial maintenance of phospholipid asymmetry in diamide-treated erythrocytes can be solely ascribed to the action of the ATP-dependent aminophospholipid translocase
-
-
-
ATP + H2O
ADP + phosphate
show the reaction diagram
-
role in aminophospholipid transport
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
role of the enzyme in the control of erythrocyte shape, possibly through association with the ATP-dependent translocation of phosphatidylserine and phosphatidylethanolamine from the outer to the inner leaflet of the bilayer
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
Q29449
phosphatidylserine is essential for the dephosphorylation of the phosphoenzyme intermediate. Without phosphatidylserine, ATPase II accumulates as phosphoenzyme in the presence of ATP, resulting in the interruption of its catalytic cycle
-
-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the enzyme is responsible for the inward transport of phosphatidylserine and phosphatidylethanolamine within the erythrocyte membrane
-
-
?
ATP + H2O + miltefosine/in
ADP + phosphate + miltefosine/out
show the reaction diagram
-
LdMT and LdRos3 form part of the same translocation machinery that determines flippase activity and miltefosine sensitivity in Leishmania
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
C7EXK4
-
-
-
?
ATP + H2O + phosphatidylethanolamine/in
ADP + phosphate + phosphatidylethanolamine/out
show the reaction diagram
Saccharomyces cerevisiae, Saccharomyces cerevisiae EHY227
-
selective ATP-dependent transport/flip of phosphatidylethanolamine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
low activity, transport from the outer to the inner leaflet of the plasma membrane, the activity is regulated by Fas-, caspase 8-, and caspase 3-dependent signaling in erythrocytes with differences in old and young red blood cells, overview
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
transport from the exoplasmic to the cytosolic leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylethanolamine/out
ADP + phosphate + phosphatidylethanolamine/in
show the reaction diagram
-
transport from the luminal leaflet of the membrane to the cytosolic leaflet
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
C7EXK4
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane to maintain lipid asymmetry in the plasma membrane and secretory vesicles
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane, exposure of PS on the surface of cells serves as a binding site for haemostatic factors, triggers cell-cell interaction and recognition by macrophages and phospholipases. Exposure of PS on the red cell surface plays a significant role in sickle cell pathology
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the membrane
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane of erythrocytes to maintainthe lipid asymmetry, overview
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
O43520
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the plasma membrane, proteins are pivotal factors in the trafficking of ATP8B1 to the plasma membrane and thus may be essential determinants of ATP8B1-related disease
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
selective ATP-dependent transport/flip of phosphatidylserine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
-
leading to reversible exposure on in the outer plasma membrane leaflet on the cell surface of cardiomyocytes by a flip-flop mechanism
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
Saccharomyces cerevisiae EHY227
-
selective ATP-dependent transport/flip of phosphatidylserine from the outer to the inner monolayer of the cell membrane and post-Golgi secretory vesicles to maintain lipid asymmetry
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
flippase activity: transport from the outer to the inner leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the exoplasmic to the cytosolic leaflet of the plasma membrane
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the external leaflet of the membrane to the inner leaflet, the enzyme controls the level of phosphatidylserine exposed to the platelet surface antagonizing to the scramblase activity, overview
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the luminal leaflet of the membrane to the cytosolic leaflet
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
show the reaction diagram
-
transport from the outer to the inner leaflet of the plasma membrane, the activity is regulated by Fas-, caspase 8-, and caspase 3-dependent signaling in erythrocytes with differences in old and young red blood cells, overview
-
-
?
ATP + H2O + phosphoethanolamine/in
ADP + phosphate + phosphoethanolamine/out
show the reaction diagram
-
low activity
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
P98200
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Q9NTI2
-
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
Dnf1p and Dnf2p are necessary for the internalization phospholipids across the plasma membrane of Saccharomyces cerevisiae, overview. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
LdMT Is required but not sufficient for the inward-directed translocation activity of phospholipids and miltefosine across the plasma membrane, LdRos3 is additionally required
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
P4-ATPases Drs2p and Dnf1p cycle between the exocytic and endocytic pathways, and maintain a steady-state localization to internal organelles requiring endocytosis signals, Drs2p is an essential endocytic cargo in cells compromised for Ub-dependent endocytosis
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
phospholipid translocases are involved in the generation of phospholipid asymmetry in membrane bilayers
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
the enzyme is involved in protein trafficking, Drs2p acts in complex with the allelic CDC50 protein in ATP-dependent phosphatidylserine translocation playing a role in restricting the substrate to the cytosolic leaflet of the Golgi and the plasma membrane, overview
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
-
transbilayer movement of phospholipids in an unidirectional fashion in biological membranes is mediated by energy-dependent and energy-independent flippases
-
-
ir
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae LMY65
-
Dnf1p and Dnf2p are necessary for the internalization phospholipids across the plasma membrane of Saccharomyces cerevisiae, overview. ATP hydrolysis is not sufficient for phospholipid flip in the absence of the proton electrochemical gradient across the plasma membrane, the proton electrochemical gradient is required for phospholipid flip across the plasma membrane of yeast
-
-
?
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae sec61
-
transbilayer movement of phospholipids in an unidirectional fashion in biological membranes is mediated by energy-dependent and energy-independent flippases
-
-
ir
ATP + H2O + phospholipid/in
ADP + phosphate + phospholipid/out
show the reaction diagram
Saccharomyces cerevisiae CCY2811
-
the enzyme is involved in protein trafficking, Drs2p acts in complex with the allelic CDC50 protein in ATP-dependent phosphatidylserine translocation playing a role in restricting the substrate to the cytosolic leaflet of the Golgi and the plasma membrane, overview
-
-
?
additional information
?
-
-
the enzyme is directly involved in miltefosine uptake in eukaryotic cells
-
-
-
additional information
?
-
-
The enzyme is essential for inward translocation of NBD-labeled phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine across the plasmamembrane.
-
-
-
additional information
?
-
-
the lipid flippase activity of enzyme is associated with its drug transport function
-
-
-
additional information
?
-
-
the membrane lipid bilayer asymmetry is maintained by the enzyme
-
-
-
additional information
?
-
-
the enzyme is a P-type ATPase involved in regulation of the lipid asymmetry of the cell membrane
-
-
-
additional information
?
-
-
the enzyme is a P-type ATPase involved in regulation of the lipid asymmetry of the cell membrane, especially Neo1p is important, Drs2p is involved in vesicle formation in the Golgi and thus influences the plasma membrane distribution of aminophospholipids despite its localization the Golgi membrane, mechanism
-
-
-
additional information
?
-
-
the Lem3p-Dnf1p complex can substitute for the Cdc50p-Drs2p complex, its redundant partner in the endosomal/trans-Golgi network compartments
-
-
-
additional information
?
-
-
endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway, overview. The homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively, these putative heteromeric PLTs share an essential function for cell growth, overview
-
-
-
additional information
?
-
-
functional co-dependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the trans-Golgi network and early endosomes of Saccharomyces cerevisiae, Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function, Drs2p physically interacts with AP-1, overview
-
-
-
additional information
?
-
-
glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity, regulation and physiological effects, overview
-
-
-
additional information
?
-
-
loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, overview
-
-
-
additional information
?
-
Q6UQ17
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
-
additional information
?
-
-
isozyme Drs2p interacts with the guanine nucleotide exchange factor Gea2p involved in activation of ADP-ribosylation factors, isozyme Neo1p interacts with the guanine nucleotide exchange factor Ysl2p/Mon2p and the Arf Arl1p, and cooperation between these three proteins is important for recruitment of clathrin adaptors
-
-
-
additional information
?
-
P98200
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
Q9NTI2
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
C7EXK4
Atp8a2 flipps fluorescent-labeled phosphatidylserine from the inner leaflet of liposomes, equivalent to the exocytoplasmic leaflet of cell membranes, to the outer leaflet, equivalent to cytoplasmic leaflet, in an ATP-dependent manner
-
-
-
additional information
?
-
Saccharomyces cerevisiae EHY227
-
loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
dependent on
Mg2+
-
-
Mg2+
Q6UQ17
ATP8B3 accepts the gamma-phosphate from ATP during the catalytic cycle in the presence of Mg2+
Mg2+
C7EXK4
required
Mg2+
P98200
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-monoolein
-
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
-
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
4-hydroxy-2-nonenal
-
-
AlFx
P60752
trapping of MsbA with 0.8 mM AlFx results in incomplete inhibition of activity
-
azide
-
-
BeFx
P60752
trapping of MsbA with 0.8 mM BeFx results in incomplete inhibition of activity
-
Ca2+
-
0.0002 mM, inhibits from the cytofacial surface
Ca2+
-
-
Cd2+
-
-
cholesterol
-
the transport activity of P-glycoprotein decreases by about 20% cholesterol
cyclosporin A
-
inhibition of phospholipid flipping
Diamide
-
-
DTNB
-
-
elaiophylin
-
partial inhibition of Mg+-ATPase activity, translocation of phosphatidylserine is almost completely abolished
eosin Y
-
almost complete inhibition of both Mg2+-ATPase activity and translocation
F-
-
inhibition increases in the presence of 0.01 mM AlCl3
F-
-
NaF
Kes1p
-
Kes1p represses the flippase activity of Drs2p in trans-Golgi network membranes
-
lipid A
P60752
lipid A inhibits translocation by approx. 30% at 0.01-0.04 mg/ml
NEM
C7EXK4
over 90% inhibition of ATPase activity at 1 mM
orthovanadate
-
-
phosphate analogue Vi
P60752
the presence of 0.1-0.2 m M Vi inhibits flippase activity of MsbA by approx. 50%
-
pyridyldithioethylamine
-
-
sulfhydryl reagents
-
-
suramin
-
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
-
biphasic inhibition
vanadate
-
inhibits the enzyme from the cytofacial surface
vanadate
-
75% inhibition of ATP hydrolysis at 0.1 mM vanadate
vanadate
-
maximal half-inhibition at 0.035 mM
vanadate
-
-
vanadate
C7EXK4
over 90% inhibition of ATPase activity at 0.1 mM
vanadyl ion
-
inhibits the enzyme from the extracellular surface
verapamil
-
inhibition of phospholipid flipping
verapamil
-
complete inhibition at 0.05 mM
vinblastine
-
inhibition of phospholipid flipping
methyl-beta-cyclodextrin
-
transport of 0.001 mM tetramethylrosamine is essentially abolished by 1 mM methyl-beta-cyclodextrin, and transport of 0.005 mM H33342 is almost completely inhibited by 5 mM methyl-beta-cyclodextrin
additional information
P60752
neither lipopolysaccharide from the Ra mutant of Escherichia coli nor deep rough chemotype lipopolysaccharide affect MsbA flippase activity significantly
-
additional information
C7EXK4
no inhibition by ouabain and azide
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-aminonaphthalene-8-sulfonate
-
stimulates
1-heptanesulfonate
-
stimulates
2,4-Dinitrophenol
-
stimulates, stimulation is prevented by 0.2-1.0 mM Ca2+
4-Aminosalicylate
-
stimulates
acidic phospholipids
-
acidic phospholipids, specifically cardiolipin, bind the co-purified EpsE/cyto-EpsL complex and stimulate its ATPase activity 30-130fold, whereas the activity of EpsE alone is unaffected. Removal of the last 11 residues, residues 243-253, from cyto-EpsL prevented cardiolipin binding as well as stimulation of the ATPase activity of EpsE
-
ALIS protein
-
-
-
ATP
-
biphasic activation, K0.5 = 0.02 mM and 0.4 mM
ATP
P60752
flippase activity is essentially supported only by ATP. If the ATP concentration in the assay falls below 5 mM, there is a significant decrease in flippase activity. Maximal translocation occurs at 10 mM ATP
Benzoate
-
stimulates
Brij
-
stimulates
-
cardiolipin
-
binds the co-purified EpsE/cyto-EpsL complex and stimulates its ATPase activity 30-130fold, whereas the activity of EpsE alone is unaffected. Removal of the last 11 residues, residues 243-253, from cyto-EpsL prevents cardiolipin binding as well as stimulation of the ATPase activity of EpsE
CDC50 proteins
O43520
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
-
CDC50A
-
-
-
cholate
-
stimulates
cholate
-
slightly increases the efflux of phospholipids and cholesterol from cells
cholesterol
-
the transport activity of P-glycoprotein is elevated by about 40% cholesterol
dithiothreitol
-
partially stimulates
glycerophosphoserine
-
prevents transport of phosphatidylserine
glycocholate
-
slightly increases the efflux of phospholipids and cholesterol from cells
p-hydroxyphenylacetate
-
stimulates
p-nitrophenol
-
stimulates
phenylacylbromide
-
-
Phenylglyoxal
-
-
phosphatidylethanolamine
-
slight activation
phosphatidylethanolamine
C7EXK4
activates to a lesser degree
phosphatidylglycerol
-
slight activation
phosphatidylhomoserine
-
slight activation
phosphatidylhydroxypropionate
-
slight activation
phosphatidylserine
-
2.1fold activation, Atp8a1 is activated only by the naturally occurring sn-1,2-glycerol isomer of PS and not the sn-2,3-glycerol stereoisomer
phosphatidylserine
C7EXK4
-
Phospholipids
-
The activity of purified MsbA is dependent upon the presence of phospholipids.
protein Drs2p
-
coupled to the enzyme, required for the translocation of phospholipids from the luminal leaflet of the membrane to the cytosolic leaflet in the trans-Golgi network, overview
-
salicylate
-
stimulates
SDS
-
stimulates
sulfanilamide
-
stimulates
Sulfanilic acid
-
stimulates
taurocholate
-
increases the efflux of phospholipids and cholesterol from cells, the taurocholate monomer plays an important role in ABCB4-mediated lipid secretion
Tetradecyltrimethylammonium bromide
-
stimulates
Thrombin
-
induces platelet phosphatidylserine exposure, inhibited by c7E3 or SR121566
-
Triton X-100
-
stimulates
verapamil
-
a P-glycoprotein modulator known to stimulate ATPase activity in a biphasic manner at micromolar concentrations
Kdo2-lipid A
-
-
additional information
-
the secretory granule Atp8a1 is activated by phospholipids binding to a specific site whose properties (PS selectivity, dependence upon glycerol but not serine, stereochemistry, and vanadate sensitivity) are similar to, but distinct from, the properties of the substrate binding site of the plasma membrane flippase, no activation by N-methylphosphatidylserine, phosphatidylserine-O-methyl ester, lysophosphatidylserine, glycerophosphoserine, and phosphoserine, Atp8a1 activities are insensitive to the stereochemistry of the serine headgroup of activating phospholipid
-
additional information
-
glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity
-
additional information
-
effects of bile salt structure on ABCB4-mediated lipid secretion, overview
-
additional information
-
Lem3p interacts and sustains functionality of isozymes Dnf1p and Dnf2p
-
additional information
P60752
GTP, AMP and AMP-PNP yield low levels of translocation compared to ATP
-
additional information
C7EXK4
no activation by phosphatidylcholine or other membrane lipids
-
additional information
-
zVAD, a pancaspase inhibitor, and TcdB, a caspase 3 inductor, induces membrane flip-flop in H9c2 cells, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.03
acetyl phosphate
-
phosphatase activity
1.31
acetyl phosphate
-
phosphatidylserine translocase activity
0.211
ATP
-
phosphatase activity
0.225
ATP
-
phosphatidylserine translocase activity
0.704
ATP
Q9NTI2
pH 7.5, 37C
1.17
p-nitrophenyl phosphate
-
phosphatase activity, detection of p-nitrophenolate formation from trichloroacetic acid precipitates
1.39
p-nitrophenyl phosphate
-
phosphatidylserine translocase activity
1.46
p-nitrophenyl phosphate
-
phosphatase activity, continous detection of p-nitrophenolate formation in ghost at neutral pH
0.878
ATP
-
pH 7.5, 37C, KM value of purified, detergent-solubilized MsbA, whereas the KM value calculated in the presence of 0.05 mM KdO2-lipid A is decreased by more than half
additional information
additional information
-
Km for translocation expressed as percent of total membrane phospholipid is 0.14% for spin-labeled phosphatidylserine and 1.19% for spin-labeled phosphatidylethanolamine
-
additional information
additional information
-
-
-
additional information
additional information
C7EXK4
Michaelis-Menten kinetics, overview
-
additional information
additional information
Q9NTI2
kinetics, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.002 - 0.004
-
activity of purified, detergent-solubilized MsbA
0.054
C7EXK4
purified native enzyme, pH 7.5, 37C
2.3
-
Atp8a1 in Sf21 cell lysate, in absence of phosphatidylserine
4.9
-
Atp8a1 in Sf21 cell lysate, in presence of phosphatidylserine
35
C7EXK4
purified native enzyme reconstituted in lipid vesicles, pH 7.5, 37C
45 - 55
Q9NTI2
purified lipid-stimulated enzyme, pH 7.5, 37C
additional information
-
-
additional information
-
flippase activity detected with unlabeled lipids by shape changes of giant unilamellar vesicles
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8.5
-
-
7 - 9
C7EXK4
with substrate phosphatidylserine
7
-
assay at
8
C7EXK4
with substrate phosphatidylethanolamine
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23
C7EXK4
flippase assay at
23
Q9NTI2
flippase assay at
37
O43520
assay at
37
-
assay at
37
C7EXK4
ATPase assay at
37
Q9NTI2
ATPase assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
below 4C transport of phospholipids is inhibited in both erythrocytes and fibroblasts, warming to 7C activates transport in fibroblasts
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
epithelial cells
Manually annotated by BRENDA team
-
the enzyme occurs only in the platelet fraction which does not expose phosphatidylserine
Manually annotated by BRENDA team
-
synaptosomes
Manually annotated by BRENDA team
O60312
the ATP10C demonstrates imprinted, preferential maternal expression in brain
Manually annotated by BRENDA team
Q148W0
low distribution in brain
Manually annotated by BRENDA team
-
adult ventricular
Manually annotated by BRENDA team
-
neonatal rat cardiomyoblasts
Manually annotated by BRENDA team
-
canalicular membrane
Manually annotated by BRENDA team
Q148W0
high distribution in pancreas
Manually annotated by BRENDA team
P98200
disc membranes
Manually annotated by BRENDA team
Q9NTI2
disc membranes
Manually annotated by BRENDA team
C7EXK4
disc membranes
Manually annotated by BRENDA team
-
expression analysis of isozymes Atp8a1 and flippase in reticulocytes, overview
Manually annotated by BRENDA team
P98200
outer segment disc membranes of rod and cone photoreceptor cells
Manually annotated by BRENDA team
Q9NTI2
outer segment disc membranes of rod and cone photoreceptor cells, high expression of atp8a2
Manually annotated by BRENDA team
C7EXK4
outer segment disc membranes of rod and cone photoreceptor cells, high expression of atp8a2
Manually annotated by BRENDA team
Q148W0
high distribution in small intestine
Manually annotated by BRENDA team
Q6UQ17
ATP8B3 is expressed only in germ cells, especially in haploid spermatids
Manually annotated by BRENDA team
Q6UQ17
exclusively expressed in testes
Manually annotated by BRENDA team
Q9NTI2
high expression of atp8a2
Manually annotated by BRENDA team
C7EXK4
high expression of atp8a2
Manually annotated by BRENDA team
additional information
-
distribution of isozyme expression in different cells, overview
Manually annotated by BRENDA team
additional information
-
no endogenous ABCB4 activity in HEK-293 cells
Manually annotated by BRENDA team
additional information
Q9NTI2
localization study by immunofluorescence microscopy
Manually annotated by BRENDA team
additional information
C7EXK4
localization study by immunofluorescence microscopy
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q6UQ17
localized in developing acrosomes
-
Manually annotated by BRENDA team
-
AP-1 is required, and GGA proteins, Golgi localized, gamma-ear containing, Arf-binding proteins acting as chlatrin adaptos, are dispensable, for efficient exclusion of Drs2p from exocytic vesicles targeted to the plasma membrane
Manually annotated by BRENDA team
Saccharomyces cerevisiae CCY2811
-
-
-
Manually annotated by BRENDA team
-
EpsE is a cytoplasmic component of the type II secretion system
Manually annotated by BRENDA team
-
ATP9B is able to exit the endoplasmic reticulum in the absence of exogenous CDC50 expression
Manually annotated by BRENDA team
Q9Y2Q0
in the absence of CDC50A
Manually annotated by BRENDA team
O43520
ATP8B1 in absence of CDC50A and CDC50
Manually annotated by BRENDA team
-
Cdc50p-Drs2p complex
Manually annotated by BRENDA team
-
loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the trans Golgi network, AP-1 is required at the trans Golgi network to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome
Manually annotated by BRENDA team
-
Drs2p and Dnf3p are localized in the trans Golgi network
Manually annotated by BRENDA team
-
Drs2p, which has multiple endocytosis signals, including two NPFXDs near the C terminus and PEST-like sequences near the N terminus that may mediate ubiquitin-dependent endocytosis, localizes to the trans-Golgi network in wild-type cells and accumulates on the plasma membrane when both the Ub- and NPFXD-dependent endocytic mechanisms are inactivated, the C-terminal and N-terminal NPFXD motifs ar functionally required by Drs2p and Drf1p, overview
Manually annotated by BRENDA team
-
loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the trans Golgi network, AP-1 is required at the trans Golgi network to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome
Manually annotated by BRENDA team
-
ATP9B localizes to the trans-Golgi network in a CDC50 protein-independent manner
Manually annotated by BRENDA team
Q9Y2Q0
upon coexpression with CDC50A, flippase ATP8A1 translocates to the Golgi complex and plasma membrane
Manually annotated by BRENDA team
Saccharomyces cerevisiae EHY227
-
Drs2p and Dnf3p are localized in the trans Golgi network
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae CCY2811
-
trans Golgi network
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae CCY2811
-
-
-
Manually annotated by BRENDA team
-
trans-Golgi network membranes
Manually annotated by BRENDA team
-
preparation of microparticles for in vitro assay
Manually annotated by BRENDA team
O43520
CDC50A and CDC50B are pivotal factors in the trafficking of ATP8B1 to the plasma membrane and thus may be essential determinants of ATP8B1-related disease
Manually annotated by BRENDA team
-
internalization of Dnf1p from the plasma membrane uses an NPFXD endocytosis signal and its recognition by Sla1p, part of an endocytic coat/adaptor complex with clathrin, Pan1p, Sla2p/End4p, and End3p
Manually annotated by BRENDA team
-
loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the trans Golgi network
Manually annotated by BRENDA team
P98204
the enzyme localizes to the plant plasma membrane and has a strict requirement for an ALIS protein beta-subunit to exit the endoplasmic reticulum
Manually annotated by BRENDA team
Q9Y2Q0
upon coexpression with CDC50A, flippase ATP8A1 translocates to the Golgi complex and plasma membrane
Manually annotated by BRENDA team
Saccharomyces cerevisiae EHY227, Saccharomyces cerevisiae LMY65, Saccharomyces cerevisiae CCY2811
-
-
-
Manually annotated by BRENDA team
-
post-Golgi, Drs2p is incorporated into the low-density class of secretory vesicles
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae EHY227
-
post-Golgi, Drs2p is incorporated into the low-density class of secretory vesicles
-
-
Manually annotated by BRENDA team
-
Cdc50p and Drs2p are localized to the trans-Golgi network and late endosome
Manually annotated by BRENDA team
Saccharomyces cerevisiae sec61
-
-
-
-
Manually annotated by BRENDA team
additional information
-
chromaffine granules
-
Manually annotated by BRENDA team
additional information
-
P4-ATPases Drs2p and Dnf1p cycle between the exocytic and endocytic pathways, and maintain a steady-state localization to internal organelles requiring endocytosis
-
Manually annotated by BRENDA team
additional information
Q9NTI2
localization study by immunofluorescence microscopy
-
Manually annotated by BRENDA team
additional information
C7EXK4
localization study by immunofluorescence microscopy
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
160000
Q6UQ17
SDS-PAGE
701167
170000
-
SDS-PAGE
700292
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 110000, SDS-PAGE
?
-
x * 120000, recombinant His-tagged Atp8a1, SDS-PAGE
?
-
x * 140000, recombinant ABCB4, SDS-PAGE
?
Q9NTI2
x * 132000, about, recombinant enzyme, SDS-PAGE
?
C7EXK4
x * 132000, recombinant enzyme, SDS-PAGE
homodimer
P60752
2 * 65000, SDS-PAGE
additional information
-
the C-tail is essential for Drs2p function in protein transport bearing the functionally required NPFXD motifs, Drs2p and Drf1p both contain an N-terminally located NPFXD motif, located in the cytoplasmic tail in Drf1p, importnat for activity, overview
additional information
-
the homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively, Cdc50 family proteins form complexes with Drs2 family proteins, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
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
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 35 days, stored erythrocytes show pH-dependently reduced flippase activity and ATP depletion, upon ATP supply the activity can be restored, overview
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP8A1 from chromaffin granules
-
native Atp8a2 1887fold from photoreceptor outer segments by immunoaffinity chromatography
C7EXK4
concanavalin A-Sepharose 4B affinity column chromatography and Sephadex G50 gel filtration
-
Ni-NTA column chromatography
P60752
recombinant wild-type and mutant enzymes
-
partial
-
partially from erythrocytes
-
recombinant enzyme from HEK-293 cells by immunoaffinity chromatography
Q9NTI2
recombinant His-tagged Atp8a1 from Spodoptera frugiperda Sf21 cells by microsome preparation and nickel affinity chromatography
-
native enzyme from chromaffin granules
-
native enzymes partially by subcellular fractionation
-
partially by microsome preparation
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Saccharomyces cerevisiae strain w303-1a
P98204
gene atp8a2, DNA and amino acid sequence determination and analysis, expression of 1D4-tagged Atp8a2 in HEK-293 cells
C7EXK4
the gene MsbA is cloned into pET28b behind the T7 promoter in-frame with an N-terminal His6tag
-
ATP10C
O60312
gene atp8a2, DNA and amino acid sequence determination and analysis, expression in HEK-293 cells
Q9NTI2
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
O43520
stable expression of ABCB4 in HEK-293 cells
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LdMT is cloned by rescuing the resistance phenotype of the M-40 R cell line overexpression in Leishmania tarentolae
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expressed in COS-7 cells
Q6UQ17
expressed in UPS-1 cells
Q148W0
expression of His-tagged Atp8a1 in Spodoptera frugiperda Sf21 cells using the baculovirus transfection system
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gene atp8a2, DNA and amino acid sequence determination and analysis, expression in HEK-293 cells
P98200
Creation and study of strains lacking Dnf1, Dnf2 or both Dnf1 and Dnf2. The double mutant is defective in the inward translocalisation of NBD-labeled phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine across the plasmamembrane. The loss of both Dnf1 and Dnf2 leads to an increased cell surface exposure of endogenous aminophospholipids. The double mutant is sensitive to low concentrations of Co2+, Ni2+, Zn2+, and Mn2+
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expression of GFP-tagged Drs2p and HA-tagged Drf1p wild-type and mutant enzymes in Saccharomyces cerevisiae, subcloning in Escherichia coli strains XL1-Blue and DH5alpha
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gene swa4, DNA and amino acid sequence determination and anaylsis, comparison to the allelic gene cdc50
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genes DRS2, DNF1 and DNF2, and DNF3, expression of wild-type and mutant enzymes, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
coexpression of CDC50A increased the total cellular expression level of flippase ATP8A1
Q9Y2Q0
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A270T
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mutant and wild-type enzymes have similar activities at 30C, but the mutant activity is decreased significant at 42C
K1075M
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site-directed mutagenesis in the Walker A motif results in an inactive mutant
G308V
Q148W0
Atp8b1 protein is virtually undetectable in G308V mouse liver, the G308V substitution results in an instable protein that cannot exit the endoplasmic reticulum and is broken down by the proteasome
F511L
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the mutant has a specific activity that is 35% that of wild type Drs2
K435M
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site-directed mutagenesis in the Walker A motif results in an inactive mutant
additional information
O43520
mutations in isozyme ATP8B1 cause progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1, overview
F511Y
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the mutant retains wild type activity, the substitution in Drs2 specifically abrogates phosphatidylserine recognition by this flippase causing phosphatidylserine exposure on the outer leaflet of the plasma membrane without disrupting phospatidylethanolamine asymmetry
additional information
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lem3 mutants are not affected in Lem3p-Dnf1p complex formation, but show a synthetic growth defect with the null mutation CDC50, overview
additional information
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simultaneous inactivation of Dnf2p and Dnf1p abolishes the ATP-dependent influx of phosphatidylserine and phosphatidylethanolamine into the cell
additional information
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a conditional allele that inactivates Drs2p phospholipid translocase activity disrupts its own transport in this AP-1 pathway, missorting of Drs2p to the plasma membrane of AP-1 mutants, cell surface accumulation of GFP-Drs2p is less pronounced in apm1DELTA and nearly absent in apm2DELTA cells treated with latrunculin A, overview
additional information
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construction of deletion mutants of phosphilipid translocases and CDC50 proteins, phenotypes, detailed overview
additional information
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construction of yeast knockout strains lacking Drs2p and/or Drf1p activity, the pan1-20 temperature-sensitive mutant is constitutively defective for Ub-dependent endocytosis but is not defective for NPFXD-dependent endocytosis at the permissive growth temperature. To sustain viability of pan1-20, Drs2p must be endocytosed through the NPFXD/Sla1p pathway
additional information
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deletion mutants of drs2 and cdc50, DELTAdrs2 and DELTAcdc50, exhibit a clathrin-deficient phenotype with delayed transport of carboxypeptidase Y to the vacuole, mislocation of resident TGN enzymes and the accumulation of aberrant membrane structures, the mutations cause a loss in plasma membrane phosphatidylserine asymmetry leading to disruption of protein trafficking, phenotypes, overview
additional information
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loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, removal of P4 ATPases Dnf1p and Dnf2p from budding yeast abolishes inward translocation of 6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminocaproyl] (NBD)-labeled phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine across the plasma membrane and causes cell surface exposure of endogenous phosphatidylethanolamine, overview
Y618F
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acquisition of the phosphatidylserine substrate maps to a Tyr618Phe substitution in transmembrane segment 4 of Dnf1. The rate of 7-nitrobenz-2oxa-1,3-diazol-4-yl phospholipid uptake by Dnf1 Y618F is comparable to wild type Dnf1
additional information
Saccharomyces cerevisiae CCY2811
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deletion mutants of drs2 and cdc50, DELTAdrs2 and DELTAcdc50, exhibit a clathrin-deficient phenotype with delayed transport of carboxypeptidase Y to the vacuole, mislocation of resident TGN enzymes and the accumulation of aberrant membrane structures, the mutations cause a loss in plasma membrane phosphatidylserine asymmetry leading to disruption of protein trafficking, phenotypes, overview
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additional information
Saccharomyces cerevisiae EHY227
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loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles, removal of P4 ATPases Dnf1p and Dnf2p from budding yeast abolishes inward translocation of 6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminocaproyl] (NBD)-labeled phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine across the plasma membrane and causes cell surface exposure of endogenous phosphatidylethanolamine, overview
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Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified Atp8a2 is reconstituted into liposomes containing fluorescent-labeled phosphatidylserine to measure the ability of Atp8a2 to flip phosphatidylserine across the lipid bilayer. 30% of the reconstituted Atp8a2 is inaccessible to trypsin and correspondingly ATP
C7EXK4
preparation of proteoliposomes for enzyme reconstitution using microsome and liposomes, overview
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
O60312
The enzyme gene is an interesting candidate for chromosome 15-associted autism and it can contribute to the Angelman syndrome phenotype.
medicine
Q148W0
ATP8B1 deficiency leads to reduced PS flipping and impaired farnesoid X receptor signaling via impaired PKCgamma-mediated nuclear translocation of farnesoid X receptor, resulting in reduced bile salt export pump and enhanced apical sodium-dependent bile salt transporter activation
additional information
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Drs2p deficiency causes a markedly increased rate of cholesterol transport from the plasma membrane to the endoplasmic reticulum and redistribution of endogenous ergosterol to intracellular membranes