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Information on EC 7.6.2.2 - ABC-type xenobiotic transporter and Organism(s) Rattus norvegicus and UniProt Accession Q08201

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IUBMB Comments
An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. The enzymes from Gram-positive bacteria and eukaryotic cells export a number of drugs with unusual specificity, covering various groups of unrelated substances while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them also transport glutathione---drug conjugates (see EC 7.6.2.3, ABC-type glutathione-S-conjugate transporter) while others also show some 'flippase' activity (cf. EC 7.6.2.1, P-type phospholipid transporter).
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Rattus norvegicus
UNIPROT: Q08201
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hide
ATP
+
H2O
+
xenobiotic[side 1]
=
ADP
+
phosphate
+
xenobiotic[side 2]
+
+
xenobiotic[side 1]
=
+
+
xenobiotic[side 2]
Synonyms
p-glycoprotein, abcb1, abcg2, atp-binding cassette transporter, abcc2, breast cancer resistance protein, abcc1, multidrug resistance-associated protein, mdr1a, multidrug transporter, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
multidrug resistance protein 2
-
phosphatidylcholine translocator
-
ABCC2
ATP phosphohydrolase (xenobiotic-exporting)
-
-
-
-
breast cancer resistance protein
-
-
MRP
-
-
-
-
multidrug resistance protein 1
-
-
multidrug resistance-associated protein 2
multidrug-resistance protein
-
-
-
-
P-glycoprotein
Pgp
-
-
-
-
transporter protein MRP
-
-
-
-
xenobiotic-transporting ATPase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (ABC-type, xenobiotic-exporting)
An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. The enzymes from Gram-positive bacteria and eukaryotic cells export a number of drugs with unusual specificity, covering various groups of unrelated substances while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them also transport glutathione---drug conjugates (see EC 7.6.2.3, ABC-type glutathione-S-conjugate transporter) while others also show some 'flippase' activity (cf. EC 7.6.2.1, P-type phospholipid transporter).
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + H2O + phosphatidylcholine/in
ADP + phosphate + phosphatidylcholine/out
show the reaction diagram
-
-
-
?
3alpha-sulfatolithocholyltaurine/in + ATP + H2O
3alpha-sulfatolithocholyltaurine/out + ADP + phosphate
show the reaction diagram
-
-
-
?
ATP + H2O + 2,4-dinitrophenyl-S-glutathione[side 1]
ADP + phosphate + 2,4-dinitrophenyl-S-glutathione[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine[side 1]
ADP + phosphate + 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + cyclosporin A/in
ADP + phosphate + cyclosporin A/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + dexamethasone/in
ADP + phosphate + dexamethasone/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + diltiazem/in
ADP + phosphate + diltiazem/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + GSSG/in
ADP + phosphate + GSSG/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + methotrexate[side 1]
ADP + phosphate + methotrexate[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + ochratoxin A[side 1]
ADP + phosphate + ochratoxin A[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + rhodamine 123/in
ADP + phosphate + rhodamine 123/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + ritonavir/in
ADP + phosphate + ritonavir/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + ritonavir[side 1]
ADP + phosphate + ritonavir[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + S-2,4-dinitrophenylglutathione/in
ADP + phosphate + S-2,4-dinitrophenylglutathione/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + saquinavir[side 1]
ADP + phosphate + saquinavir[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + trans-resveratrol[side 1]
ADP + phosphate + trans-resveratrol[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + verapamil/in
ADP + phosphate + verapamil/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + vinblastine/in
ADP + phosphate + vinblastine/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + vinblastine[side 1]
ADP + phosphate + vinblastine[side 2]
show the reaction diagram
-
-
-
?
ATP + H2O + xenobiotic/in
ADP + phosphate + xenobiotic/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + xenobiotic[side 1]
ADP + phosphate + xenobiotic[side 2]
show the reaction diagram
-
-
-
?
cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu)/in + ATP + H2O
cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu)/out + ADP + phosphate
show the reaction diagram
-
no other common substrate detected
-
?
estradiol 17-beta-D-glucuronide/in + ATP + H2O
estradiol 17-beta-D-glucuronide/out + ADP + phosphate
show the reaction diagram
-
-
-
-
?
GSH/in + ATP + H2O
GSH/out + ADP + phosphate
show the reaction diagram
-
-
-
?
leukotriene C4/in + ATP + H2O
leukotriene C4/out + ADP + phosphate
show the reaction diagram
-
-
-
?
leukotriene D4/in + ATP + H2O
leukotriene D4/out + ADP + phosphate
show the reaction diagram
-
-
-
-
?
S-(2,4-dinitrophenyl)glutathione/in + ATP + H2O
S-(2,4-dinitrophenyl)glutathione/out + ADP + phosphate
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 + phosphatidylcholine/in
ADP + phosphate + phosphatidylcholine/out
show the reaction diagram
-
-
-
?
ATP + H2O + xenobiotic/in
ADP + phosphate + xenobiotic/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + xenobiotic[side 1]
ADP + phosphate + xenobiotic[side 2]
show the reaction diagram
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cyclosporin A
-
inhibits transport of dexamethasone, ritonavir and vinblastine
estradiol 17beta-D-glucuronide
-
competitive inhibition of the transport activity of Mdr2
glyceollins
-
-
poly(acrylic acid)cysteine
-
-
procyanidin
-
markedly increases the accumulation of rhodamine 123 by inhibiting its efflux in a dose-dependent manner. A 5-fold increase in cellular Rh123 is observed for procyanidine at 0.01 mM. Procyanidine is a potent inhibitor of P-glycoprotein on blood-brain barrier and can improve the therapeutic effects on cerebral tumors of some drugs which are difficult to accumulate in the brain
quinidine
-
inhibits transport of dexamethasone, ritonavir and vinblastine
verapamil
-
inhibits transport of dexamethasone, ritonavir and vinblastine
additional information
-
ethynylestradiol selectively diminishes the expression of Mdr2 in the intestine, no inhibition of expression of breast cancer resistance protein, of Mrp3, and expression of multidrug resistance protein 1 is only minimally impaired
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
carbamazepine
-
Phenobarbital
-
spironolactone
-
additional information
-
spironolactone induced Mdr2 expression
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017
cyclo(D-Trp-D-Asp-L-Pro-D-Val-L-Leu)/in
-
-
0.111
GSSG/in
-
-
0.00025
leukotriene C4/in
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
highest expression
Manually annotated by BRENDA team
-
plasma membrane vesicles from brain microvessel endothelial cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MDR3_RAT
1278
10
140655
Swiss-Prot
other Location (Reliability: 5)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
glycosylation is not essential for ATPase or transport function, the N-linked oligosaccharides appear to influence the conformation of the protein in a subtle way
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Sf9 cell vesicles
-
gene Mdr2, quantitative expression analysis in the intestine, overview
-
two forms of abcb1a are cloned from Sprague-Dawley cDNA that differ by six amino acids and a base pair deletion. The intact form is stably transfected in LLC-PK1 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the Mdr2 protein is not detected in livers from male and female rats at birth while mRNA is consistently expressed in livers at a high and steady level until 30 days of age
erucin, glyceollins, soybean extract, sulforaphane, 5'-fluorouracil, bortezomib, bosentan, carbamazepine, cimetidine, cisplatin A, efavirenz, mitotane, obatoclax, pregnenolone-16alpha-carbonitrile, quinidine, saquinavirm spironolactone, vincristine, rifampicin, and tripanocide benznidazole induce enzyme mRNA expression
resveratrol, 8-hydroxydaidzein. atorvastatin, epirubicin, ethanol, irinotecan, isopentanol, and topotecan downregulate enzyme mRNA expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
procyanidine is a potent inhibitor of P-glycoprotein on blood-brain barrier and can improve the therapeutic effects on cerebral tumors of some drugs which are difficult to accumulate in the brain
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sharom, F.J.; Liu, R.; Romsicki, Y.; Lu, P.
Insight into the structure and substrate interactions of the P-glycoprotein multidrug transporter from spectroscopic studies
Biochim. Biophys. Acta
1461
327-345
1999
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Keppler, D.; Knig, J.; Buchler, M.
The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes
Adv. Enzyme Regul.
37
321-333
1997
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Madon, J.; Hagenbuch, B.; Landmann, L.; Meier, P.J.; Stieger, B.
Transport function and hepatocellular localization of mrp6 in rat liver
Mol. Pharmacol.
57
634-641
2000
Rattus norvegicus, Rattus norvegicus MRP6
Manually annotated by BRENDA team
Misra, S.; Ujhazy, P.; Varticovski, L.; Arias, I.M.
Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles
Proc. Natl. Acad. Sci. USA
96
5814-5819
1999
Rattus norvegicus
Manually annotated by BRENDA team
Katoh, M.; Suzuyama, N.; Takeuchi, T.; Yoshitomi, S.; Asahi, S.; Yokoi, T.
Kinetic analyses for species differences in P-glycoprotein-mediated drug transport
J. Pharm. Sci.
95
2673-2683
2006
Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Booth-Genthe, C.L.; Louie, S.W.; Carlini, E.J.; Li, B.; Leake, B.F.; Eisenhandler, R.; Hochman, J.H.; Mei, Q.; Kim, R.B.; Rushmore, T.H.; Yamazaki, M.
Development and characterization of LLC-PK1 cells containing Sprague-Dawley rat Abcb1a (Mdr1a): comparison of rat P-glycoprotein transport to human and mouse
J. Pharmacol. Toxicol. Methods
54
78-89
2006
Rattus norvegicus
Manually annotated by BRENDA team
Arias, A.; Villanueva, S.S.; Ruiz, M.L.; Luquita, M.G.; Veggi, L.M.; Pellegrino, J.M.; Vore, M.; Catania, V.A.; Mottino, A.D.
Regulation of expression and activity of rat intestinal multidrug resistance-associated protein 2 by cholestatic estrogens
Drug Metab. Dispos.
37
1277-1285
2009
Rattus norvegicus
Manually annotated by BRENDA team
He, L.; Zhao, C.; Yan, M.; Zhang, L.Y.; Xia, Y.Z.
Inhibition of P-glycoprotein function by procyanidine on blood-brain barrier
Phytother. Res.
23
933-937
2009
Rattus norvegicus
Manually annotated by BRENDA team
Zhang, Q.; Yang, W.; Song, H.; Wu, H.; Lu, Y.; He, J.; Zhao, D.; Chen, X.
Tissue distribution and ontogeny of multidrug resistance protein 2, a phosphatidylcholine translocator, in rats
Eur. J. Drug Metab. Pharmacokinet.
41
87-91
2016
Rattus norvegicus (Q08201)
Manually annotated by BRENDA team
Tocchetti, G.N.; Rigalli, J.P.; Arana, M.R.; Villanueva, S.S.M.; Mottino, A.D.
Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics
Toxicol. Appl. Pharmacol.
303
45-57
2016
Homo sapiens (Q92887), Rattus norvegicus (Q92887)
Manually annotated by BRENDA team