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Information on EC 7.6.2.1 - P-type phospholipid transporter and Organism(s) Mus musculus and UniProt Accession P98197
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7.6.2.1 P-type phospholipid transporterIUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. Different forms of the enzyme move phospholipids such as phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidyglycerol, sphingomyelin and glucosylceramide from one membrane face to the other ('flippase').
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Word Map
- 7.6.2.1
- leaflet
- cholestasis
-
aminophospholipids
- bile
-
asymmetry
- erythrocyte
-
intrahepatic
- atpases
- ca2+-atpase
- na+
- myosin
- biliary
-
canalicular
-
abcb11
-
k+-atpase
- phosphatidylethanolamine
-
scramble
-
actin-activated
- actomyosin
-
ca2+-dependent
-
flip-flop
- p-glycoproteins
- na+,k+-atpase
-
pro12ala
-
ca2+-activated
-
ursodeoxycholic
- cholelithiasis
- ouabain
- hepatobiliary
-
exoplasmic
- gallstone
-
o-antigens
- pruritus
- gizzard
-
proteoliposomes
-
lipid-linked
-
cholangiopathy
- meromyosin
-
3.6.1.3
-
actin-myosin
-
ptdser
-
ppargamma2
-
ca2+-stimulated
-
superprecipitation
- fr
-
ca2+-pumping
- analysis
- prothrombinase
-
photophosphorylation
- molecular biology
- undecaprenyl
- medicine
-
subfragment-1
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Synonyms
mg2+-atpase, abcb4, flippase, plscr1, atp8b1, scramblase, aminophospholipid translocase, ala12, tat-2, drs2p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminophospholipid flippase
aminophospholipid flippase 10
-
-
-
-
aminophospholipid flippase 11
-
-
-
-
aminophospholipid flippase 12
-
-
-
-
aminophospholipid translocase
aminophospholipid translocase VC
-
-
-
-
ATP8A1
ATP8B3
ATPase II
-
-
-
-
ATPVC
-
-
-
-
ATPVD
-
-
-
-
flippase
HUSSY-20
-
-
-
-
Mg2+-ATPase
-
-
-
-
Mg2+-ATPase A
-
-
-
-
phospholipid flippase
-
additional information
aminophospholipid flippase
-
-
-
-
aminophospholipid translocase
-
-
-
-
flippase
-
-
-
-
additional information
the enzyme belongs to the phospholipid flippases or scramblases
additional information
the enzyme belongs to the P4-ATPase subfamily of the of P-type ATPases
additional information
the enzyme belongs to the phospholipid flippases or scramblases
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, phospholipid-flipping)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. Different forms of the enzyme move phospholipids such as phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidyglycerol, sphingomyelin and glucosylceramide from one membrane face to the other ('flippase').
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + phosphatidylethanolamine[side 1]
ADP + phosphate + phosphatidylethanolamine[side 2]
-
-
-
?
ATP + H2O + phosphatidylserine[side 1]
ADP + phosphate + phosphatidylserine[side 2]
-
-
-
?
ATP + H2O + phospholipid[side 1]
ADP + phosphate + phospholipid[side 2]
-
-
-
?
ATP + H2O + phosphatidylethanolamine[side 1]
ADP + phosphate + phosphatidylethanolamine[side 2]
-
-
-
?
ATP + H2O + phosphatidylserine/out
ADP + phosphate + phosphatidylserine/in
-
-
-
?
ATP + H2O + phosphatidylserine[side 1]
ADP + phosphate + phosphatidylserine[side 2]
-
-
-
?
ATP + H2O + phospholipid[side 1]
ADP + phosphate + phospholipid[side 2]
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
-
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
-
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
-
selective ATP-dependent transport of phosphatidylserine from the outer to the inner monolayer of the cell membrane to maintain lipid asymmetry
-
-
?
additional information
?
-
PLSCR1 acts as signaling molecule and is involved in redistribution of plasma membrane phospholipids triggered by increased cytosolic Ca2+. The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
PLSCR1 acts as signaling molecule and is involved in redistribution of plasma membrane phospholipids triggered by increased cytosolic Ca2+. The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
calcium-induced phospholipid scrambling is bidirectional, reversible and insensitive to phospholipid head group, PLSCR1 is neither sufficient nor necessary for the phosphatidylserine externalization
-
-
?
additional information
?
-
calcium-induced phospholipid scrambling is bidirectional, reversible and insensitive to phospholipid head group, PLSCR1 is neither sufficient nor necessary for the phosphatidylserine externalization
-
-
?
additional information
?
-
calcium-induced phospholipid scrambling is bidirectional, reversible and insensitive to phospholipid head group, the scramblase catalyzes the externalization of phosphatidylserine to the cell surface
-
-
?
additional information
?
-
calcium-induced phospholipid scrambling is bidirectional, reversible and insensitive to phospholipid head group, the scramblase catalyzes the externalization of phosphatidylserine to the cell surface
-
-
?
additional information
?
-
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
?
additional information
?
-
-
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
?
additional information
?
-
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + phospholipid[side 1]
ADP + phosphate + phospholipid[side 2]
-
-
-
?
ATP + H2O + phospholipid[side 1]
ADP + phosphate + phospholipid[side 2]
-
-
-
?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
-
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
-
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
-
-
?
additional information
?
-
PLSCR1 acts as signaling molecule and is involved in redistribution of plasma membrane phospholipids triggered by increased cytosolic Ca2+. The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
PLSCR1 acts as signaling molecule and is involved in redistribution of plasma membrane phospholipids triggered by increased cytosolic Ca2+. The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
The enzyme plays a role in apoptosis, lipid metabolism, and thrombosis, and is involved in the Scott syndrome, detailed overview
-
-
?
additional information
?
-
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
?
additional information
?
-
-
ATP8B3 may play a role in acrosome development and/or in sperm function during fertilization
-
-
?
additional information
?
-
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Ca2+
activates, dependent on for redistibution of plasma membrane phospholipids, the enzyme contains a EF-hand-like Ca2+ binding motif, overview
Ca2+
dependent on for redistibution of plasma membrane phospholipids, the enzyme contains a EF-hand-like Ca2+ binding motif, overview
Mg2+
ATP8B3 accepts the gamma-phosphate from ATP during the catalytic cycle in the presence of Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
AMP-PNP
-
N-ethylmaleimide
-
NaF
-
vanadate
-
AMP-PNP
-
N-ethylmaleimide
-
NaF
-
vanadate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
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
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
-
-
-
-
-
-
expression analysis of isozymes Atp8a1 and flippase in reticulocytes, overview
ATP8B3 is expressed only in germ cells, especially in haploid spermatids
additional information
-
-
-
-
additional information
-
distribution of isozyme expression in different cells, overview
additional information
PLSCR4 is not expressed in peripheral blood lymphocytes
additional information
PLSCR4 is not expressed in peripheral blood lymphocytes
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
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 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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AT11A_MOUSE
1187
7
135502
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 120000, SDS-PAGE
?
x * 120000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
lipoprotein
PLSCR1 contains a palmitoylation motif as the site of palmitoylation by a thioester linkage to the sulfhydryl groups of cysteines that regulates its trafficking either to nucleus or to the plasma membrane
lipoprotein
PLSCR4 contains a palmitoylation motif as the site of palmitoylation by a thioester linkage to the sulfhydryl groups of cysteines that regulates its trafficking either to nucleus or to the plasma membrane
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E181Q
the mutant shows strongly reduced activity compared to the wild type enzyme
E186Q
inactive
E181Q
the mutant shows strongly reduced activity compared to the wild type enzyme
E186Q
inactive
G308V
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged Atp8a1 from Spodoptera frugiperda Sf21 cells by microsome preparation and nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence analysis, PLSCR1, PLSCR2 and PLSCR4 are closely clustered on the small arm of chromosome 3q23
expression of His-tagged Atp8a1 in Spodoptera frugiperda Sf21 cells using the baculovirus transfection system
-
gene atp8a2, DNA and amino acid sequence determination and analysis, expression in HEK-293 cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sahu, S.K.; Gummadi, S.N.; Manoj, N.; Aradhyam, G.K.
Phospholipid scramblases: an overview
Arch. Biochem. Biophys.
462
103-114
2007
Homo sapiens (O15162), Homo sapiens (Q9NRQ2), Homo sapiens (Q9NRY6), Homo sapiens (Q9NRY7), Mus musculus (P58196), Mus musculus (Q9JJ00), Caenorhabditis elegans (Q21318)
Paterson, J.K.; Renkema, K.; Burden, L.; Halleck, M.S.; Schlegel, R.A.; Williamson, P.; Daleke, D.L.
Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II)
Biochemistry
45
5367-5376
2006
Mus musculus
Soupene, E.; Kuypers, F.A.
Identification of an erythroid ATP-dependent aminophospholipid transporter
Br. J. Haematol.
133
436-438
2006
Mus musculus
Folmer, D.E.; Elferink, R.P.; Paulusma, C.C.
P4 ATPases - Lipid flippases and their role in disease
Biochim. Biophys. Acta
1791
628-635
2009
Mus musculus (Q148W0), Mus musculus
Gong, E.Y.; Park, E.; Lee, H.J.; Lee, K.
Expression of Atp8b3 in murine testis and its characterization as a testis specific P-type ATPase
Reproduction
137
345-351
2009
Mus musculus (Q6UQ17), Mus musculus
Coleman, J.A.; Kwok, M.C.; Molday, R.S.
Localization, purification, and functional reconstitution of the P4-ATPase Atp8a2, a phosphatidylserine flippase in photoreceptor disc membranes
J. Biol. Chem.
284
32670-32679
2009
Bos taurus (C7EXK4), Mus musculus (P98200), Homo sapiens (Q9NTI2)
Siggs, O.M.; Arnold, C.N.; Huber, C.; Pirie, E.; Xia, Y.; Lin, P.; Nemazee, D.; Beutler, B.
The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow
Nat. Immunol.
12
434-440
2011
Mus musculus (Q9QZW0)
Wang, J.; Molday, L.L.; Hii, T.; Coleman, J.A.; Wen, T.; Andersen, J.P.; Molday, R.S.
Proteomic analysis and functional characterization of P4-ATPase phospholipid flippases from murine tissues
Sci. Rep.
8
10795
2018
Mus musculus (O54827), Mus musculus (P70704), Mus musculus (P98197), Mus musculus (P98199), Mus musculus (P98200), Mus musculus (Q148W0), Mus musculus (Q6DFW5), Mus musculus (Q6UQ17), Mus musculus (Q8K2X1), Mus musculus (Q9QZW0), Mus musculus
EXTERNAL LINKS (specific for EC-Number 7.6.2.1)
Transporter Classification Database (TCDB): 3.A.3.8.1, 3.A.3.8.13, 3.A.3.8.8, 3.A.3.8.11, 3.A.1.211.13, 3.A.3.8.14, 8.A.17.1.1, 3.A.3.8.15, 3.A.3.8.2, 3.A.3.8.5, 3.A.3.8.4, 3.A.3.8.18, 3.A.3.8.20, 3.A.1.201.3, 3.A.3.8.24, 3.A.3.8.7, 3.A.3.8.9, 3.A.3.8.6, 3.A.3.8.16, 3.A.1.211.14, 3.A.1.211.1, 3.A.1.201.1, 3.A.3.8.26, 3.A.3.8.25, 3.A.3.8.17, 3.A.3.8.12, 3.A.1.211.5, 3.A.1.211.2, 3.A.1.211.10, 3.A.3.8.10, 3.A.3.8.3
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