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Information on EC 7.6.2.1 - P-type phospholipid transporter and Organism(s) Rattus norvegicus and UniProt Accession D4AA47

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IUBMB 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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Rattus norvegicus
UNIPROT: D4AA47
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Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
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
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aminophospholipid flippase
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aminophospholipid flippase 10
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-
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aminophospholipid flippase 11
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aminophospholipid flippase 12
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aminophospholipid translocase
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aminophospholipid translocase VC
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ATP-independent flippase
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ATP-independent long-chain phosphatidylcholine translocator
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ATPase II
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ATPVC
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-
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ATPVD
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flippase
glycerophospholipid flippase
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HUSSY-20
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M5-DLO flippase
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Mg2+-ATPase
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Mg2+-ATPase A
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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transmembrane transport
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, phospholipid-flipping)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. 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 hide
9000-83-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1D-myo-inositol 1-O-myristoyl-2-O-[6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino-hexanoyl]-sn-glycer-3-yl]-phosphate/in
1D-myo-inositol 1-O-myristoyl-2-O-[6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino-hexanoyl]-sn-glycer-3-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
-
-
?
1D-myo-inositol 1-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-3-yl]-phosphate/in
1D-myo-inositol 1-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-3-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
-
-
?
1D-myo-inositol 3-O-myristoyl-2-O-[6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino-hexanoyl]-sn-glycer-1-yl]-phosphate/in
1D-myo-inositol 3-O-myristoyl-2-O-[6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino-hexanoyl]-sn-glycer-1-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
-
-
?
1D-myo-inositol 3-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-1-yl]-phosphate/in
1D-myo-inositol 3-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-1-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
-
-
?
1L-myo-inositol 1-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-3-yl]-phosphate/in
1L-myo-inositol 1-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-3-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
-
-
?
1L-myo-inositol 3-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-1-yl]-phosphate/in
1L-myo-inositol 3-O-[1-[6'-([6-[(7-nitro-2-oxa-1,3-diazolobenz-4-yl)amino]-hexanoyl]amino)hexanoyl]-2-O-stearoyl-sn-glycer-1-yl]-phosphate/out
show the reaction diagram
-
fluorescence-labeled substrate, proteoliposomes generated from flippase-enriched Triton X-100 extract of endoplasmic reticulum or native endoplasmic vesicles, overview
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-
?
ATP + H2O
ADP + phosphate
show the reaction diagram
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
ATP + phospholipid/out
ADP + phosphate + phospholipid/in
show the reaction diagram
long-chain phospholipid/out
long-chain phospholipid/in
show the reaction diagram
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-
-
-
?
Man5GlcNAc2-diphosphate-dolichol/out
Man5GlcNAc2-diphosphate-dolichol/in
show the reaction diagram
-
ATP-independent flipping
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-
?
phosphatidylcholine/in
phosphatidylcholine/out
show the reaction diagram
-
proteoliposomes generated from aminophospholipid translocase-enriched Triton X-100 extract of endoplasmic reticulum
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-
?
phosphatidylcholine/out
phosphatidylcholine/in
show the reaction diagram
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L-alpha-1-palmitoyl-2-linoleoyl-labeled substrate
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-
?
phosphatidylethanolamine/in
phosphatidylethanolemine/out
show the reaction diagram
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proteoliposomes generated from aminophospholipid translocase-enriched Triton X-100 extract of endoplasmic reticulum
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-
?
phosphatidylethanolamine/out
phosphatidylethanolamine/in
show the reaction diagram
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?
phosphatidylserine/in
phosphatidylserine/out
show the reaction diagram
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proteoliposomes generated from aminophospholipid translocase-enriched Triton X-100 extract of endoplasmic reticulum
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-
?
phospholipid/in
phospholipid/out
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O
ADP + phosphate
show the reaction diagram
-
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
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?
ATP + H2O + phosphatidylserine/in
ADP + phosphate + phosphatidylserine/out
show the reaction diagram
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leading to reversible exposure on in the outer plasma membrane leaflet on the cell surface of cardiomyocytes by a flip-flop mechanism
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?
ATP + phospholipid/out
ADP + phosphate + phospholipid/in
show the reaction diagram
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the enzyme is essential for ATP-independent externalization of long-chain phospholipids from hepatocytes and secretion to the bile across the canalicular plasma membrane
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?
phospholipid/in
phospholipid/out
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
diethyldicarbonate
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rat liver contains two populations, DEPC-sensitive and DEPC-insensitive, of flippases, which can be in a different of DEPC sensitivity or be two different proteins
NEM
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rat liver contains two populations of, NEM-sensitive and NEM-insensitive, flippases, which can be in a different of NEM sensitivity or be two different proteins
additional information
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no inhibition by verapamil, no effect by ATP
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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aminophospholipid translocase transbilayer movement stopped flow-kinetics in the reconstituted system or intact ER-vesicles with different fluorescence-labeled substrates
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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assay at
7.2
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at
23
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assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the predominant P4 ATPases in pure pancreatic beta cells and pancreatic islets are ATP8B1, ATP8B2, and ATP9A. ATP8B1 and CDC50A are highly concentrated in insulin secretory granules
Manually annotated by BRENDA team
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adult ventricular
Manually annotated by BRENDA team
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neonatal rat cardiomyoblasts
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
gene silencing of individual P4 ATPases and CDC50A inhibits glucose-stimulated insulin release in pure beta cells and in human pancreatic islets
physiological function
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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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AT8B1_RAT
1251
10
143834
Swiss-Prot
other Location (Reliability: 1)
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from liver endoplasmic reticulum
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of the purified native enzyme in proteoliposomes using phospholipids and Triton X-100 at pH 7.5 and 22°C
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Devaux, P.F.; Zachowski, A.; Morrot, G.; Cribier, S.; Fellmann, P.; Geldwerth, D.; Bitbol, M.; Herve, P.
Control of the transmembrane phospholipid distribution in eukaryotic cells by aminophospholipid translocase
Biotechnol. Appl. Biochem.
12
517-522
1990
Bos taurus, Cavia porcellus, Homo sapiens, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Fuchs, M.; Carey, M.C.; Cohen, D.E.
Evidence for an ATP-independent long-chain phosphatidylcholine translocator in hepatocyte membranes
Am. J. Physiol. Gastrointest. Liver Physiol.
273
1312-1319
1997
Rattus norvegicus, no activity in Xenopus laevis
Manually annotated by BRENDA team
Chang, Q.L.; Gummadi, S.N.; Menon, A.K.
Chemical modification identifies two populations of glycerophospholipid flippase in rat liver ER
Biochemistry
43
10710-10718
2004
Rattus norvegicus
Manually annotated by BRENDA team
Devaux, P.F.; Lopez-MOntero, I.; Bryde, S.
Proteins involved in lipid translocation in eukaryotic cells
Chem. Phys. Lipids
141
119-132
2006
Bos taurus, Saccharomyces cerevisiae, Homo sapiens, Leishmania infantum, Rattus norvegicus
Manually annotated by BRENDA team
Vishwakarma, R.A.; Vehring, S.; Mehta, A.; Sinha, A.; Pomorski, T.; Herrmann, A.; Menon, A.K.
New fluorescent probes reveal that flippase-mediated flip-flop of phosphatidylinositol across the endoplasmic reticulum membrane does not depend on the stereochemistry of the lipid
Org. Biomol. Chem.
3
1275-1283
2005
Rattus norvegicus
Manually annotated by BRENDA team
Sanyal, S.; Menon, A.K.
Specific transbilayer translocation of dolichol-linked oligosaccharides by an endoplasmic reticulum flippase
Proc. Natl. Acad. Sci. USA
106
767-772
2009
Rattus norvegicus
Manually annotated by BRENDA team
Krijnen, P.A.; Sipkens, J.A.; Molling, J.W.; Rauwerda, J.A.; Stehouwer, C.D.; Muller, A.; Paulus, W.J.; van Nieuw Amerongen, G.P.; Hack, C.E.; Verhoeven, A.J.; van Hinsbergh, V.W.; Niessen, H.W.
Inhibition of Rho-ROCK signaling induces apoptotic and non-apoptotic PS exposure in cardiomyocytes via inhibition of flippase
J. Mol. Cell. Cardiol.
49
781-790
2010
Rattus norvegicus
Manually annotated by BRENDA team
Ansari, I.U.; Longacre, M.J.; Paulusma, C.C.; Stoker, S.W.; Kendrick, M.A.; MacDonald, M.J.
Characterization of P4 ATPase phospholipid translocases (flippases) in human and rat pancreatic beta cells: their gene silencing inhibits insulin secretion
J. Biol. Chem.
290
23110-23123
2015
Rattus norvegicus (D4AA47), Homo sapiens (O43520), Homo sapiens (P98198), Homo sapiens (Q2NLD0), Homo sapiens
Manually annotated by BRENDA team