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Information on EC 7.2.2.9 - P-type Cu2+ transporter and Organism(s) Mus musculus and UniProt Accession Q64446
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7.2.2.9 P-type Cu2+ transporterIUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme from the termophilic archaeon Archaeoglobus fulgidus is involved in copper extrusion from the cell [1,2].
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Word Map
- 7.2.2.9
-
3.6.1.3
- ceruloplasmin
- cisplatin
- atpases
-
copper-dependent
-
x-linked
- na+
- platinum
- triphosphatase
-
trans-golgi
-
metal-binding
- biliary
- overload
-
copper-binding
-
disease-causing
- metallothioneins
-
k+-atpase
- oxaliplatin
- ouabain
-
copper-induced
- carboplatin
-
platinum-based
- mg2+-atpase
-
toxicosis
-
occipital
-
kayser-fleischer
- copa
- adenosinetriphosphatase
- na+,k+-atpase
- phosphoenzyme
- d-penicillamine
-
cisplatin-resistant
- ferroxidase
-
mottled
-
long-evans
-
copper-containing
-
copperi
- tetrathiomolybdate
-
copper-deficient
-
metallochaperone
-
kinky
- cinnamon
-
k+-stimulated
-
cddp-resistant
-
multicopper
- bathocuproine
- medicine
-
cu-induced
- drug development
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3.1.3.5
-
terrier
-
k+-dependent
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
atp7b, atp7a, copper transporter, copper-transporting atpase, copper-transporting p-type atpase, menkes protein, cu-atpase, copper transporting p-type atpase, wilson disease protein, copper atpase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
adenosine 5'-triphosphatase
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-
-
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ATP hydrolase
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-
-
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ATP phosphohydrolase
-
-
-
-
ATP7A
ATP7B
ATPase
-
-
-
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complex V
-
-
-
-
Cu2+-ATPase
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-
-
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CUA-1 ATPase
-
-
-
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Menkes disease-associated protein
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-
-
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Menkes disease-associated protein homolog
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-
-
-
Menkes P-type ATPase
-
-
-
-
MNK
Pinal night-specific ATPase
-
-
-
-
WCBD
-
-
-
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Wilson copper-transporting P-type ATPase
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-
-
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Wilson disease copper-transporting ATPase
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-
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Wilson disease protein
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-
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Wilson disease-associated protein
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-
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Wilson disease-associated protein homolog
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-
-
-
additional information
-
ATP7A and ATP7B are members of the P1B-subfamily of the P-type ATPases
ATP7B
-
-
-
-
MNK
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
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-
-
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transmembrane transport
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, Cu2+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme from the termophilic archaeon Archaeoglobus fulgidus is involved in copper extrusion from the cell [1,2].
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
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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 + Cu2+/in
ADP + phosphate + Cu2+/out
because the Wilson protein delivers copper to the ferroxidase ceruloplasminm in the liver, it is likely that the Wilson and/or Menkes proteins provide copper to cerulopliasmin made in the retinal pigment epithelium
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
-
vascular Menkes ATPase plays an essential role in full activity of superoxide dismutase SOD3 through transporting copper to SOD3 in the trans-Golgi network, thereby regulating superoxide anion levels in the vasculature
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
age-dependent expression studies in kidney, role for ATP7A in renal response to changes in copper load
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
immunodetection studies in cells and tissues to analyze specific roles for ATP7A and ATP7B
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
key role of ATP7A in the basolateral export of copper, immunodetection studies
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
role for ATP7B in regulation of renal copper shown
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
role of ATP7A in delivery of copper to milk using transgenic mice that over-express human ATP7A
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
role of ATP7A in protective effect of copper in neuronal cells
-
-
?
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 + Cu2+/in
ADP + phosphate + Cu2+/out
because the Wilson protein delivers copper to the ferroxidase ceruloplasminm in the liver, it is likely that the Wilson and/or Menkes proteins provide copper to cerulopliasmin made in the retinal pigment epithelium
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
-
vascular Menkes ATPase plays an essential role in full activity of superoxide dismutase SOD3 through transporting copper to SOD3 in the trans-Golgi network, thereby regulating superoxide anion levels in the vasculature
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithioerythritol
-
GSH, dithiothreitol or dithioerythritol are required for activity
dithiothreitol
-
GSH, dithiothreitol or dithioerythritol are required for activity
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
ATP7A xpressed to a variable degree throughout the kidney, age-dependent intracellular localization, copper elevation results in the in vivo redistribution of ATP7A from intracellular compartments toward the basolateral membrane, ATP7A plays a major role in exporting copper via basolateral membranes and protects renal tissue against copper overload
additional information
ATP7A xpressed to a variable degree throughout the kidney, age-dependent intracellular localization, copper elevation results in the in vivo redistribution of ATP7A from intracellular compartments toward the basolateral membrane, ATP7A plays a major role in exporting copper via basolateral membranes and protects renal tissue against copper overload
additional information
connection between copper homeostasis and NMDA receptor activity, ATP7A required for copper-dependent effects
additional information
copper concentration in the mammary gland reduced in transgenic mice, immunofluorescence analysis of mammary gland tissue, tissue copper concentration, mRNA levels of endogenous ATP7A and ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice, ATP7A plays a role in removing excess copper from mammary epithelial cells rather than supplying copper to milk
additional information
copper concentration in the mammary gland reduced in transgenic mice, immunofluorescence analysis of mammary gland tissue, tissue copper concentration, mRNA levels of endogenous ATP7A and ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice, ATP7A plays a role in removing excess copper from mammary epithelial cells rather than supplying copper to milk
additional information
-
copper concentration in the mammary gland reduced in transgenic mice, immunofluorescence analysis of mammary gland tissue, tissue copper concentration, mRNA levels of endogenous ATP7A and ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice, ATP7A plays a role in removing excess copper from mammary epithelial cells rather than supplying copper to milk
additional information
immunodetection studies to analyze specific roles for ATP7A and ATP7B, partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates
additional information
immunodetection studies to analyze specific roles for ATP7A and ATP7B, partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates
additional information
-
immunodetection studies to analyze specific roles for ATP7A and ATP7B, partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates
additional information
mRNA levels of endogenous ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice
additional information
mRNA levels of endogenous ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice
additional information
-
mRNA levels of endogenous ATP7B and of ATP7B protein unaltered in mammary gland of transgenic mice
additional information
partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates, specific role of ATP7B in tissues, in which it is co-expressed with ATP7A, may involve delivery of copper to ceruloplasmin, apical copper export and/or fine tuning of intracellular copper by sequestration of copper in the vesicles
additional information
partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates, specific role of ATP7B in tissues, in which it is co-expressed with ATP7A, may involve delivery of copper to ceruloplasmin, apical copper export and/or fine tuning of intracellular copper by sequestration of copper in the vesicles
additional information
-
partial overlap in the intracellular localization of ATP7A and ATP7B due to different sorting and trafficking fates, specific role of ATP7B in tissues, in which it is co-expressed with ATP7A, may involve delivery of copper to ceruloplasmin, apical copper export and/or fine tuning of intracellular copper by sequestration of copper in the vesicles
additional information
renal copper homeostasis requires functional ATP7B, coexpression with ATP7A, kidneys of ATP7b(-/-) mice reveals metabolic alterations manifested by the appearance of highly fluorescent deposits, lack of notable copper accumulation in the Atp7b(-/-) kidney due to compensatory export of copper by ATP7A
additional information
renal copper homeostasis requires functional ATP7B, coexpression with ATP7A, kidneys of ATP7b(-/-) mice reveals metabolic alterations manifested by the appearance of highly fluorescent deposits, lack of notable copper accumulation in the Atp7b(-/-) kidney due to compensatory export of copper by ATP7A
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ATP7B; 2 weeks old and 20 weeks old, wild-type and deficient in copper-transporting ATPase ATP7B (-/-)
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
airway, cell type-specific expression of ATP7A and ATP7B in airway epithelial cells
ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum
presence of ATP7A in the axons of postnatal, but not adult, optic nerve
ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum. In the developing and adult brain, ATP7A levels are greatest in the choroid plexus/ependymal cells of the lateral and third ventricles. ATP7A expression decreases in most neuronal subpopulations from birth to adulthood. ATP7A expression increases in CA2 hippocampal pyramidal and cerebellar Purkinje neurons
ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum
ATP7A protein 10fold to 20fold higher in transgenic than in control mice
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both Cu-ATPases ATP7A and ATP7B are expressed within retinal pigment epithelium
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
COMM-domain-containing 1 maintains the amount of Atp7b and facilitates recruitment of the enzyme from cytoplasmic vesicles to the trans-Golgi network membrane
COMM-domain-containing 1 maintains the amount of Atp7b and facilitates recruitment of the enzyme from cytoplasmic vesicles to the trans-Golgi network membrane
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perinuclear location of ATP7A. IFN-gamma activation of macrophages is associated with partial redistribution of ATP7A to the phagolysosomal compartment, IFN-gamma triggers the trafficking of ATP7A
additional information
-
IFN-gamma and lipopolysaccharides stimulate copper-dependent ATP7A trafficking to post-Golgi vesicles that overlap with the phagosome, overview
-
-
Menkes ATPase colocalizes with superoxide dismutase SOD3 in the trans-Golgi network of the secretory pathway
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2 week old mice, vicinity of the basolateral membrane
basolateral membrane of mammary epithelial cells in lactating mice
20 week old mice, predominantly in intracellular vesicles
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
additional information
-
Escherichia coli survival is dependent on ATP7A expression in murine RAW-264.7 macrophages. Baterial survival is significantly increased in ATP7A-depleted cells compared with control cells, and copper pretreatment of ATP7A-depleted cells restores bactericidal activity to control levels, overview. Copper enhances the bactericidal activity of macrophages
physiological function
-
ATP7A and ATP7B are two key proteins that regulate the Cu status of the body. They transport Cu across cellular membranes for biosynthetic and protective functions, enabling Cu to fulfill its role as a catalytic and structural cofactor for many essential enzymes, and to prevent a toxic build-up of Cu inside cells. A variety of regulatory mechanisms operate at transcriptional and post-translational levels to ensure adequate Cu supplies for both physiological and pathophysiological processes. In the cerebellum, Atp7a may have a homeostatic role maintaining intracellular Cu levels, while Atp7b has a biosynthetic role delivering Cu to enzymes such as ceruloplasmin. In retinal pigment epithelium ATP7A and ATP7B may control Cu transport to the outer retina, as well as Cu delivery to tyrosinase for melanogenesis within the retinal pigment epithelium, and to ceruloplasmin and hephaestin to maintain iron homeostasis
physiological function
-
ATP7A-dependent copper transport is required for bactericidal activity of RAW-264.7 macrophages
physiological function
-
expression of the copper transporter ATP7B in ciliated airway cells is required for detoxification of the methylated caffeine silver acetate compound, SCC1, in the airway epithelium. The cytotoxicity of SCC1-treated airway epithelial cell cultures derived from either wild type or ATP7B null mice littermates is compared, loss of total cells and ciliated cells is significantly greater in ATP7B-/- than in wild type airway epithelial cell
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). PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
ATP7A silencing by stable transfection of RAW-264.7 cells with ATP7A RNAi
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
COMM-domain-containing 1 knockdown reduces the expression of Atp7b, and abolishes the relocation of Atp7b back from the periphery to the trans-Golgi network membrane
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Takeda, K.; Ushimaru, M.; Fukushima, Y.; Kawamura, M.
Characterization of a P-type copper-stimulated ATPase from mouse liver
J. Membr. Biol.
170
13-16
1999
Mus musculus
Quian, Y.; Tiffany-Castiglioni, E.; Welsh, J.; Harris, E.D.
Copper efflux from murine microvascular cells requires expression of the Menkes disease Cu-ATPase
J. Nutr.
128
1276-1282
1998
Homo sapiens, Mus musculus
Qin, Z.; Itoh, S.; Jeney, V.; Ushio-Fukai, M.; Fukai, T.
Essential role for the Menkes ATPase in activation of extracellular superoxide dismutase: implication for vascular oxidative stress
FASEB J.
20
334-336
2006
Mus musculus
Krajacic, P.; Qian, Y.; Hahn, P.; Dentchev, T.; Lukinova, N.; Dunaief, J.L.
Retinal localization and copper-dependent relocalization of the Wilson and Menkes disease proteins
Invest. Ophthalmol. Vis. Sci.
47
3129-3134
2006
Homo sapiens (P35670), Homo sapiens, Mus musculus (Q64430), Mus musculus
Niciu, M.J.; Ma, X.; El Meskini, R.; Ronnett, G.V.; Mains, R.E.; Eipper, B.A.
Developmental changes in the expression of ATP7A during a critical period in postnatal neurodevelopment
Neuroscience
139
947-964
2006
Mus musculus (Q64430), Mus musculus
Linz, R.; Barnes, N.L.; Zimnicka, A.M.; Kaplan, J.H.; Eipper, B.; Lutsenko, S.
Intracellular targeting of copper-transporting ATPase ATP7A in a normal and ATP7b-/- kidney
Am. J. Physiol. Renal Physiol.
294
F53-F61
2008
Mus musculus (Q64430), Mus musculus (Q64446)
Llanos, R.M.; Michalczyk, A.A.; Freestone, D.J.; Currie, S.; Linder, M.C.; Ackland, M.L.; Mercer, J.F.
Copper transport during lactation in transgenic mice expressing the human ATP7A protein
Biochem. Biophys. Res. Commun.
372
613-617
2008
Mus musculus (Q64430), Mus musculus (Q64446), Mus musculus
Linz, R.; Lutsenko, S.
Copper-transporting ATPases ATP7A and ATP7B: cousins, not twins
J. Bioenerg. Biomembr.
39
403-407
2007
Mus musculus (Q64430), Mus musculus (Q64446), Mus musculus
Schlief, M.L.; West, T.; Craig, A.M.; Holtzman, D.M.; Gitlin, J.D.
Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity
Proc. Natl. Acad. Sci. USA
103
14919-14924
2006
Rattus norvegicus (P70705), Mus musculus (Q64430)
La Fontaine, S.; Ackland, M.L.; Mercer, J.F.
Mammalian copper-transporting P-type ATPases, ATP7A and ATP7B: emerging roles
Int. J. Biochem. Cell Biol.
42
206-209
2010
Homo sapiens, Mus musculus
White, C.; Lee, J.; Kambe, T.; Fritsche, K.; Petris, M.J.
A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity
J. Biol. Chem.
284
33949-33956
2009
Mus musculus
Ibricevic, A.; Brody, S.L.; Youngs, W.J.; Cannon, C.L.
ATP7B detoxifies silver in ciliated airway epithelial cells
Toxicol. Appl. Pharmacol.
243
315-322
2010
Mus musculus
EXTERNAL LINKS (specific for EC-Number 7.2.2.9)
Transporter Classification Database (TCDB): 3.A.3.5.12, 3.A.3.5.10
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