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Information on EC 7.2.2.8 - P-type Cu+ transporter
for references in articles please use BRENDA:EC7.2.2.8
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EC Tree 7 Translocases
7.2 Catalysing the translocation of inorganic cations
7.2.2 Linked to the hydrolysis of a nucleoside triphosphate
7.2.2.8 P-type Cu+ transporter
IUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme transports Cu+ or Ag+, and cannot transport the divalent ions, contrary to EC 7.2.2.9, P-type Cu2+ transporter, which mainly transports the divalent copper ion.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
showSynonyms
slc31a1, copt1, ctra2, cu(+)-atpase, copa1, copa2, copper-transporting atpase 2, ctra3, cu atpase, copper export atpase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AFLA_051390
ATP7A
ATP7B
CopA
CopB
copper ATPase
copper transporter
copper(I) transporting P-type ATPase
copper-exporting P-type ATPase
copper-transporting ATPase
copper-transporting P-type ATPase
COPT1
CtpB
Cu(I)-detoxifying P-type ATPase
Cu(I)-transporting ATPase
Cu(I)-transporting P-type ATPase
Cu+ transport ATPase
Cu+-ATPase
Cu+-exporting ATPase
-
-
-
-
CuTP
EC 3.6.3.54
-
-
formerly
-
LpCopA
Wilson disease protein
ATP7A
-
ATP7B
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Cu+[side 1] = ADP + phosphate + Cu+[side 2]
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, Cu+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme transports Cu+ or Ag+, and cannot transport the divalent ions, contrary to EC 7.2.2.9, P-type Cu2+ transporter, which mainly transports the divalent copper ion.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-nitrophenyl phosphate + H2O + Cu+[side 1]
4-nitrophenol + phosphate + Cu+[side 2]
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
Substrates: Ag+-ATPase activity is measured as the difference between the activity in the medium with Ag+ and that measured in the same medium without Ag+
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
Substrates: although the enzyme binds Cu+ with 15 times higher apparent affinity, Ag+ drives a faster turnover because the enzyme(Ag) form undergoes a faster dephosphorylation than the enzyme(Cu) form
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
Substrates: the enzyme is activated by Ag+ and to a lesser extent by Cu+. Maximum Cu+-ATPase activity is 25% of that measured in the presence of Ag+. However, Cu+interacts with the enzyme with higher apparent affinity. The activation by Ag+ or Cu+is dependent on the presence of millimolar amounts of cysteine. In the presence of ATP, these metals drive the formation of an acid-stable phosphoenzyme with apparent affinities similar to those observed in the ATPase activity determinations. Comparable levels of phosphoenzyme are reached in the presence of both cations. The stimulation of phosphorylation by the cations suggests that CopA drives the outward movement of the metal
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
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ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the Cu+ chaperone CopZ interacts with and delivers the metal to the Cu+-ATPase metal-binding site
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
Substrates: Tyr682, Asn683, Met711 and Ser715 are identified as required for Cu+ binding
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: although the enzyme binds Cu+ with 15 times higher apparent affinity, Ag+ drives a faster turnover because theenzyme(Ag) form undergoes a faster dephosphorylation than the enzyme(Cu) form
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the enzyme is activated by Ag+ and to a lesser extent by Cu+. Maximum Cu+-ATPase activity is 25% of that measured in the presence of Ag+.However, Cu+interacts with the enzyme with higher apparent affinity. The activation by Ag+ or Cu+is dependent on the presence of millimolar amounts of cysteine. In the presence of ATP, these metals drive the formation of an acid-stable phosphoenzyme with apparent affinities similar to those observed in the ATPase activity determinations. Comparable levels of phosphoenzyme are reached in the presence of both cations. The stimulation of phosphorylation by the cations suggests that CopA drives the outward movement of the metal
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the enzyme drives the efflux of Cu+ from the cell cytoplasm
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: mechanism of Cu+ transfer
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: catalytic proficiency of CopA is slightly higher toward its natural substrate ATP than toward 4-nitrophenyl phosphate
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: CopA forms a phosphorylated intermediate
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: in the presence of ATP, all Cu+ is released from the ATPase, dependence of metal transfer on ATP hydrolysis
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: ATP hydrolysis supplies energy for copper transport
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: metal ion binding to the N-terminal copper-sensing domain of ATP7B
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the enzyme binds Cu(II) ions that are present in the blood. It reduces the Cu(II) ions to Cu(I) and it subsequently transfers Cu(I) to the cytoplasmic domain, where the ion is delivered to various cellular pathways. H5 and H6 directly coordinate to Cu(II), whereas M7, M9, and M12 are involved in Cu(I) binding
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: Cu+-ATPase activity dependence on [Cu+] and [ATP] can both be described by a sum of two hyperbolic functions. A minimal reaction scheme for the catalytic mechanism is proposed that shares the basic reaction steps of the Albers-Post model for P-type ATPases. The reaction scheme postulated contemplates two different binding affinities for a single ATP and binding of at least 2 Cu+ with different affinities as well
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: Cu+-ATPase activity dependence on [Cu+] and [ATP] can both be described by a sum of two hyperbolic functions. A minimal reaction scheme for the catalytic mechanism is proposed that shares the basic reaction steps of the Albers-Post model for P-type ATPases. The reaction scheme postulated contemplates two different binding affinities for a single ATP and binding of at least 2 Cu+ with different affinities as well
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: Cu+ ATPase activity of CtpB in the plasma membrane shows features of high affinity/slow turnover ATPases similar to Cu+ transporting ATPases involved in protein metalation
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: metal preference for Cu+. When the concentrations of Mg2+ and ATP are constant, CtpB catalyzes ATP hydrolysis in a Cu+ concentration dependent manner
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: metal preference for Cu+. When the concentrations of Mg2+ and ATP are constant, CtpB catalyzes ATP hydrolysis in a Cu+ concentration dependent manner
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Saccharolobus solfataricus PBL2025
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
Substrates: the enzyme shows metal-stimulated ATPase activity in response to Cu+, but not Cu2+
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: cryoelectron microscopy structure of ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues lines the cytoplasmic copper entrance that is presumably gated by a conserved basic residue sitting at the center. Within the membrane, a network of copper-coordinating ligands delineates a stepwise copper transport pathway
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additional information
?
-
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Substrates: experimental evidence supports a model where the Cu+-loaded chaperone interacts with an electropositive platform formed by a kink in the second transmembrane helix of the ATPase. Subsequently, three invariant ATPase residues participate in the ligand exchange that mobilizes Cu+ from the chaperone to the transmembrane helices-metal-binding sites
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additional information
?
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Substrates: experimental evidence supports a model where the Cu+-loaded chaperone interacts with an electropositive platform formed by a kink in the second transmembrane helix of the ATPase. Subsequently, three invariant ATPase residues participate in the ligand exchange that mobilizes Cu+ from the chaperone to the transmembrane helices-metal-binding sites
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additional information
?
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Substrates: in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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?
additional information
?
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Substrates: in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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additional information
?
-
Substrates: the soluble domain of BsCopA has the same beta-alpha-beta-beta-alpha-beta structure as all proteins involved in the copper transport characterized so far
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additional information
?
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Substrates: the soluble domain of BsCopA has the same beta-alpha-beta-beta-alpha-beta structure as all proteins involved in the copper transport characterized so far
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additional information
?
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Substrates: intramolecular copper transfer within CopA metal-binding domains, quantitative analysis via analytical gel filtration, overview
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additional information
?
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Substrates: intramolecular copper transfer within CopA metal-binding domains, quantitative analysis via analytical gel filtration, overview
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additional information
?
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Substrates: in giant unilamellar vesicles, no Cu leakage or passive diffusion is found. The observed Cu uptake relies completely on active transportation
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additional information
?
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Substrates: ATP7A/B ATPase utilizes ATP through formation of a phosphoenzyme intermediate whereby phosphorylation potential affects affinity and orientation of bound cation
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additional information
?
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Substrates: detection of a positive charge displacement within a single catalytic cycle of ATP7B upon addition of ATP and formation of phosphoenzyme intermediate, C983A/C985A and C575A/C578A mutants demonstrate that ATP7B activation requires a copper binding site in the N-terminus extension
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additional information
?
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Substrates: the enzyme also shows Ag+-dependent ATPase activity
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additional information
?
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Substrates: the enzyme also shows Ag+-dependent ATPase activity
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the Cu+ chaperone CopZ interacts with and delivers the metal to the Cu+-ATPase metal-binding site
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the enzyme drives the efflux of Cu+ from the cell cytoplasm
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: CopA forms a phosphorylated intermediate
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: ATP hydrolysis supplies energy for copper transport
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: the enzyme binds Cu(II) ions that are present in the blood. It reduces the Cu(II) ions to Cu(I) and it subsequently transfers Cu(I) to the cytoplasmic domain, where the ion is delivered to various cellular pathways. H5 and H6 directly coordinate to Cu(II), whereas M7, M9, and M12 are involved in Cu(I) binding
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Saccharolobus solfataricus PBL2025
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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Substrates: -
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
Substrates: -
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additional information
?
-
-
Substrates: in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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additional information
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Substrates: in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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additional information
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Substrates: the enzyme also shows Ag+-dependent ATPase activity
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additional information
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Substrates: the enzyme also shows Ag+-dependent ATPase activity
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ag+
copper
Cu+
Cu2+
Mg2+
additional information
Ag+
-
isoform CtrA2 and CtrA3 are activated by Ag+ (with Ag+ being twice as effective as Cu+ in case of isoform CtrA2)
Ag+
full-length CopA has submicromolar affinity for Ag+, but is inhibited by concentrations above 0.001 mM. Deletion of both metal-binding domains has no effect on affinity but results in loss of this inhibition. Individual deletions implicate the N-terminal metal-binding domains in causing the inhibition at concentrations above 0.001 mM
copper
the four most N-terminal metal-binding domains in ATP7B, upon stoichiometric copper addition, adopt a more compact arrangement with higher thermal stability than in the absence of copper. No stable complex was found in solution between the metal-binding domains and the nucleotide-binding domain of ATP7B
copper
-
CopB exhibits metal-stimulated ATPase activity in response to Cu+, but not Cu2+. Cu+ is coordinated by four sulfur ligands, likely derived from conserved cysteine and methionine residues. The enzyme does bind Cu2+, the binding site is not the prototypical P1B-ATPase transmembrane site and does not involve sulfur coordination
Cu+
the enzyme contains 2.2 Cu+ and 3.1 ions Cu+ per molecule in the absence and presence of 2.5 mM ADP-Mg2+, respectively
Cu+
full-length CopA has submicromolar affinity for Cu+, but is inhibited by concentrations above 0.001 mM. Deletion of both metal-binding domains has no effect on affinity but results in loss of this inhibition. Individual deletions implicate the N-terminal metal-binding domains in causing the inhibition at concentrations above 0.001 mM
Cu+
-
Cu+ binding to the N-metal binding domain is required to produce an active conformation of the enzyme, whereby additional Cu+ bound to an alternate (transmembrane transport) site initiates faster cycles
Cu2+
copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
Cu2+
copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein expressed in rat intestinal epithelial cells. Copper has a direct influence on Atp7a protein expression independent of changes in mRNA levels
Mg2+
essential activator for the hydrolysis of 4-nitrophenylphosphate
additional information
high salt concentration stimulate the ATPase, reaching a plateau at 400500 mM. This effect appears independent of the cation, since NaCl or KCl yields similar Ag-ATPase stimulation. Experiments using N-methylglucamine to increase ionic strength in the medium could not confirm this point. Although the amine at low concentration (under 10 mM) stimulats the ATPase as NaCl or KCl, it leads to a sharp inactivation at higher concentrations
additional information
-
high salt concentration stimulate the ATPase, reaching a plateau at 400500 mM. This effect appears independent of the cation, since NaCl or KCl yields similar Ag-ATPase stimulation. Experiments using N-methylglucamine to increase ionic strength in the medium could not confirm this point. Although the amine at low concentration (under 10 mM) stimulats the ATPase as NaCl or KCl, it leads to a sharp inactivation at higher concentrations
additional information
no effect on the reaction with 4-nitrophenylphosphate: Mn2+, Co2+, Sr2+, Ba2+
additional information
-
no effect on the reaction with 4-nitrophenylphosphate: Mn2+, Co2+, Sr2+, Ba2+
additional information
-
divalent cations Cu(II), Zn(II), or Co(II) could not substitute Cu(I) or Ag(I)
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Bathocuproine disulfonate
-
i.e. BCS, Cu(I) chelator, reduces enzyme activity
cisplatin
comparison of different metal-binding domains of ATPases based on their reactivity towards cisplatin. The rate of platination is generally greater for holo-metal-binding domains than for apo-metal-binding domains. The platinum binding weakens the CuI coordination, but does not expel the copper ion from metal-binding domains; comparison of different metal-binding domains of ATPases based on their reactivity towards cisplatin. The rate of platination is generally greater for holo-metal-binding domains than for apo-metal-binding domains. The platinum binding weakens the CuI coordination, but does not expel the copper ion from metal-binding domains
Cu2+
-
binding of approximately eight Cu2+ or Zn2+ ions inhibits basal ATPase activity
glucagon
physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. The opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases PKA and PKB/Akt
glyoxal-bis(N-4,4-pyrolidine-3-thiosemicarbazonato)copper(II)
treatment of SKOV-3 cells with micromolar concentrations leads to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane
-
glyoxal-bis(N-4-methyl-3-thiosemicarbazonato)copper(II)
treatment of SKOV-3 cells with micromolar concentrations leads to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane
-
xenon
inhibition of activity of CopB copper ATPase in a soluble state or reconstituted into proteoliposomes; inhibits CopB copper ATPase both when reconstituted into proteoliposomes and in a solubilized state
Zn2+
-
binding of approximately eight Cu2+ or Zn2+ ions inhibits basal ATPase activity
vanadate
-
0.2 mM, complete inhibition. Vanadate binds irreversibly to the P-domain phosphorylation site
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition; the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition; the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
additional information
ATPase activity os almost completely suppressed by incubating CopA (1 mg/ml or 0.00633 mM) for 1 h in a solution containing 1 mM MgCl2, 0.1 mM AlCl3, 2 mM potassium fluoride in the presence of either 0.02 mM Cu+,1 mM ADP, and 0.02mM Cu+, or 0.5 mM bathocuproine disulfonate
-
additional information
-
ATPase activity os almost completely suppressed by incubating CopA (1 mg/ml or 0.00633 mM) for 1 h in a solution containing 1 mM MgCl2, 0.1 mM AlCl3, 2 mM potassium fluoride in the presence of either 0.02 mM Cu+,1 mM ADP, and 0.02mM Cu+, or 0.5 mM bathocuproine disulfonate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
asolectin
optimal activity is achieved at an asolectin molar fraction of 0.15 and an amphiphile-protein ratio of about 30000
-
cardiolipin
the hydrolytic activity of CopA is stimulated by phosphoholipid cardiolipin and to some extent by phosphatidylglycerol. The amphipathic platform helix MBC of CopA shows a significant preference for interaction with cardiolipin
Cys
millimolar concentration of Cys increase the activity about 800fold. Cys is a non-essential activator of the enzyme, interacting with the cytoplasmic side of the enzyme. K1/2 of 4 mM
Insulin
insulin reverses the effect of copper and stimulates retrograde trafficking of ATP7B from the canalicular membranes, consistent with the enhanced ability of ATP7B to sequester copper away from the cytosol. Physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. The opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases PKA and PKB/Akt
-
L-cysteine
-
isoform CtrA2 shows highest activity at 20 mM L-cysteine, isoform CtrA3 shows highest activity at 15 mM L-cysteine
phosphatidylglycerol
the hydrolytic activity of CopA is stimulated by phosphoholipid cardiolipin and to some extent by phosphatidylglycerol
cysteine
the enzyme displays a concentration-dependent Cu+ ATPase activity when the enzymatic reaction is supplemented with Cys at concentrations below 0.5 mM
Phospholipid
addition of phospholipids leads to a significant increase in CopA phosphomonoesterase turnover
Phospholipid
phospholipids enhance LpCopA Cu+-ATPase activity in a non-essential mode
additional information
-
isoform CtrA2 is activated without added lipid, whereas the activity of isoform CtrA3 depended on the addition of extraneous lipid. Escherichia coli polar lipids, soybean phosphatidyl choline, synthetic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and a total extract of Aquifex aeolicus lipids all have roughly the same effect
-
additional information
dithiothreitol is necessary in the medium to maintain the metal in its Cu(I) redox state
-
additional information
-
dithiothreitol is necessary in the medium to maintain the metal in its Cu(I) redox state
-
additional information
metal-binding domain copper-loaded MBD1 serves CopA in a chaperone-like fashion, copper-loaded metal-binding domain MBD2 shows negligible stimulation
-
additional information
-
metal-binding domain copper-loaded MBD1 serves CopA in a chaperone-like fashion, copper-loaded metal-binding domain MBD2 shows negligible stimulation
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Breast Neoplasms
Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.
Carcinoma
Effects of SLC31A1 and ATP7B polymorphisms on platinum resistance in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiotherapy.
Carcinoma, Ovarian Epithelial
ZNF711 down-regulation promotes CISPLATIN resistance in epithelial ovarian cancer via interacting with JHDM2A and suppressing SLC31A1 expression.
Cardiomyopathies
Copper deficiency and heart disease: molecular basis, recent advances and current concepts.
Cleft Lip
Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).
Colorectal Neoplasms
Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1,SCO1, and COX11 in colorectal cancer.
Esophageal Neoplasms
Association between ABCC2 polymorphism and hematological toxicity in patients with esophageal cancer receiving platinum plus 5-fluorouracil therapy.
Esophageal Squamous Cell Carcinoma
Effects of SLC31A1 and ATP7B polymorphisms on platinum resistance in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiotherapy.
Glioma
Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression.
Infections
The bacterial pathogen Xanthomonas oryzae overcomes rice defenses by regulating host copper redistribution.
Iron Deficiencies
Copper and ectopic expression of the Arabidopsis transport protein COPT1 alter iron homeostasis in rice (Oryza sativa L.).
Liver Neoplasms
Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation.
Lung Neoplasms
A pharmacogenetics study of platinum-based chemotherapy in lung cancer: ABCG2 polymorphism and its genetic interaction with SLC31A1 are associated with response and survival.
Lung Neoplasms
Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation.
Lysosomal Storage Diseases
Accounting for Protein Subcellular Localization: A Compartmental Map of the Rat Liver Proteome.
Neoplasms
Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen.
Neuroblastoma
Carnosine modulates the Sp1-Slc31a1/Ctr1 copper-sensing system and influences copper homeostasis in murine CNS-derived cells.
Osteosarcoma
PTBP1 modulates osteosarcoma chemoresistance to cisplatin by regulating the expression of the copper transporter SLC31A1.
Ototoxicity
Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity.
Squamous Cell Carcinoma of Head and Neck
Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.
Starvation
Cu-sensing transcription factor Mac1 coordinates with the Ctr transporter family to regulate Cu acquisition and virulence in Aspergillus fumigatus.
Starvation
Molecular Characteristics of the Conserved Aspergillus nidulans Transcription Factor Mac1 and Its Functions in Response to Copper Starvation.
Starvation
Molecular characterization of a putative Arabidopsis thaliana copper transporter and its yeast homologue.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00045
Cu+
-
apparent Km-value of C14A/C17A/C110A/C113A mutant protein, pH 6.8, 20°C
additional information
additional information
-
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type, and mutants M158A, M158C, E205A, E205C, D336A, D336C and S139A/G140A
-
additional information
additional information
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type, and mutants M158A, M158C, E205A, E205C, D336A, D336C and S139A/G140A
-
additional information
additional information
kinetic parameters for phosphorylation and dephosphorylation of CopA
-
additional information
additional information
-
Cu+-ATPase activity kinetic parameters and binding stoichiometry of recombinant wild-type and mutant enzymes, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
free Cu+/ATPase activity kinetic parameters and binding stoichiometry pf wild type, and mutants M158A, M158C, E205A, E205C, D336A, D336C and S139A/G140A
-
additional information
additional information
free Cu+/ATPase activity kinetic parameters and binding stoichiometry pf wild type, and mutants M158A, M158C, E205A, E205C, D336A, D336C and S139A/G140A
-
additional information
additional information
kinetic parameters for phosphorylation and dephosphorylation of CopA
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.012
Cu+ ATPase activity obtained for CtpB recombinant membranes, pH 7.4, 37°C
0.266
solubilized enzyme, presence of phospholipids and xenon, pH 6.5, 37°C
additional information
additional information
ATPase hydrolysis rates of purified and reconstituted wild-type CopA and enzyme truncation mutants
additional information
-
ATPase hydrolysis rates of purified and reconstituted wild-type CopA and enzyme truncation mutants
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.1
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 9
pH 5.5: about 20% of maximal activity, pH 9.0: about 45% of maximal activity
6 - 7
pH 6.0: about 30% of maximal activity, pH 7.0: about 30% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
60
75
60
Cu+-ATPase activity reaches the maximum at 60°C and is 4.4% of the maximum at 30°C
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 37
4°C: about 15% of maximal activity, 37°C: maximal activity
60 - 80
60°C: about 55% of maximal activity, 80°C: about 75% of maximal activity
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Saccharolobus solfataricus PBL2025
-
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
brenda
-
differentiation, interzone and early fixation zones of nodule
brenda
Cu levels regulate the reversible trafficking of endogenous ATP7B in polarized WIF-B cells
brenda
-
hepatocate cell line. Expressions of zatp7b exceeds expression of zatp7a by 15-fold
brenda
additional information
select areas of the brain, including the developing central nervous system
brenda
low activity in adipocytes, medium activity in glandular cells and myoepithelial cells
brenda
not detected in adipocytes, medium activity in glandular cells and myoepithelial cells
brenda
COPT1 is more expressed in roots than in stems and leaves
brenda
COPT2 and COPT3 are similarly expressed in roots and stems, but lower in leaves. In the case of COPT4, the highest expression is detected in the leaves and very low levels are observed in roots
brenda
Cu2+ directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
brenda
enzyme ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon. Addition of high Cu2+ concentrations cause loss of somatodendritic polarity of ATP7B. High Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
brenda
dopamine-beta-hydroxylase-containing neurons express ATP7B
brenda
dopamine-beta-hydroxylase-containing neurons express both ATP7A and ATP7B
brenda
not detected in follicle cells, low activity in ovarian stroma cells
brenda
high activity in follicle cells, not detected in ovarian stroma cells
brenda
high activity in trophoblastic cells, no detected in decidual cells
brenda
medium activity in trophoblastic cells, low activity in decidual cells
brenda
COPT1 is more expressed in roots than in stems and leaves
brenda
COPT2 and COPT3 are similarly expressed in roots and stems, but lower in leaves. In the case of COPT4, the highest expression is detected in the leaves and very low levels are observed in roots
brenda
COPT1 is more expressed in roots than in stems and leaves
brenda
COPT2 and COPT3 are similarly expressed in roots and stems, but lower in leaves
brenda
medium activity in glandular cells, not detected in squamous epithelial cells
brenda
medium activity in glandular cells and in squamous epithelial cells
brenda
high activity in squamous epithelial cells, low activity in cells in endometrial stroma
brenda
low activity in squamous epithelial cells, not detected in cells in endometrial stroma
brenda
additional information
Cu-directed trafficking of both endogenous and exogenous ATP7B
brenda
additional information
Cu-directed trafficking of both endogenous and exogenous ATP7B
brenda
additional information
-
CuTP is expressed in all Plasmodium life cycle stages, including intracellular asexual and sexual blood stages, and extracellular ookinetes and salivary gland sporozoites, and localizes to vesicle-like structures
brenda
additional information
-
CuTP is expressed in all Plasmodium life cycle stages, including intracellular asexual and sexual blood stages, and extracellular ookinetes and salivary gland sporozoites, and localizes to vesicle-like structures
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
luminal acidification is required for the cell to redirect ATP7B to the apical domain and maintain it there under conditions of high Cu. Deacidification prevents Cu-directed delivery to apical domain
brenda
in noradrenergic neurons ATP7B is vesicular and distributed throughout the cytosol
brenda
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
brenda
in noradrenergic neurons ATP7A is perinuclear and clustered at the side of the nucleus
brenda
additional information
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
brenda
Cu2+ directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
brenda
at basal copper levels in the cells, the enzyme is located in the trans-Golgi network. As the intracellular copper increases, the protein translocates to the cytoplasmic vesicles in proximity of basolateral (ATP7A) or apical (ATP7B) membranes, subsequently the vesicles fuse with the plasma membrane releasing copper ions out of the cells
brenda
a second di-leucine motif in the carboxy tail of ATP7A (1459LL) is essential for steady-state localization in the trans-Golgi network by functioning in endosome-to-trans-Golgi network trafficking. Multiple di-leucine signals are required for recycling ATP7A from the plasma membrane to the trans-Golgi network
brenda
-
TgCuTP localizes to intraparasitic structures juxtaposed to the acidocalcisomes and/or plant-like vacuole
brenda
integral membrane protein
brenda
-
integral membrane protein
-
brenda
an integral membrane protein of cytoplasmic membranes
brenda
under basal Cu2+ conditions, ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon
brenda
enzyme localization at high copper concentration
brenda
enzyme localization at high copper concentration. Deacidification prevents Cu-directed delivery to apical domain
brenda
upon copper elevation, ATP7B moves from the trans-Golgi network to specialized vesicles, following copper depletion, ATP7B returns from vesicles to the trans-Golgi network
brenda
Cu2+-regulated, dileucine-dependent localization of ATP7B to the neuronal trans-Golgi network. Under basal Cu2+ conditions, ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon. Addition of high Cu2+ concentrations cause loss of trans-Golgi network localization and somatodendritic polarity of ATP7B. ATP7B co-localizes with sigma1B, as well as with the endogenous gamma subunit at the trans-Golgi network
brenda
enzyme localization at low copper concentration
brenda
the dimeric structure is retained during ATP7B trafficking between the intracellular compartments
brenda
upon copper elevation, ATP7B moves from the trans-Golgi network to specialized vesicles, following copper depletion, ATP7B returns from vesicles to the trans-Golgi network
brenda
ATP7B incorporation into AP-1-containing clathrin-coated vesicles. Addition of high Cu2+ concentrations reduce ATP7B incorporation into AP-1-containing clathrin-coated vesicle
brenda
Cu induces an increase in the number of ATP7B vesicles, which traverse large basolateral endosomes en route to the apical domain
brenda
-
enzyme CuTP is predominantly located in vesicular bodies of the parasite
brenda
-
enzyme CuTP is predominantly located in vesicular bodies of the parasite
-
brenda
additional information
copper regulates the intracellular localization of copper transporter ATP7B, transient interactions between the N-terminal metal-binding domains and modulated intracellular localization of ATP7B, molecular mechanism
-
brenda
additional information
-
TgCuTP localizes in close proximity of the acidocalcisomes and/or plant-like vacuole in Toxoplasma gondii
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
physiological function
additional information
drug target
ATP7A and ATP7B are therapeutic targets for regulating both tumor growth in ovarian cancer and the efficacy of platinum-based medicine treatment. Correlation between overexpression of ATP7A or ATP7B, resistance to platinum-based medicine treatments, and cross-resistance to Cu
drug target
silencing of ATP7A is able to inhibit LOX activity and, as a result, to suppress LOX-dependent mechanisms of tumor progression. ATP7A-deficient tumor cells exhibit a reduced ability to generate metastasis due to poor activation of FAK1 and low cell motility
evolution
the enzyme belongs to the PIB-ATPase family, phylogenetic analysis and tree
evolution
-
an evolutionarily highly conserved, copper-transporting P-type ATPase in the murine malaria model parasite Plasmodium berghei
evolution
the enzme belongs to the superfamily of P-type ATPases, which are capable of exporting transition metal ions at the expense of ATP hydrolysis. P1BATPases share a conserved structure of three cytoplasmic domains linked by a transmembrane domain. In addition, they possess a unique class of domains located at the N-terminus. P1B-ATPases show general functional divergence of tandem metal-binding domains, which is governed by the length of the inter-domain linker
evolution
-
an evolutionarily highly conserved, copper-transporting P-type ATPase in the murine malaria model parasite Plasmodium berghei
-
evolution
Saccharolobus solfataricus PBL2025
-
the enzyme belongs to the PIB-ATPase family, phylogenetic analysis and tree
-
malfunction
-
the copA mutant loses more than half of wild-type levels of copper resistance along with the ability to retain viability during cultivation on chalcopyrite
malfunction
-
mutation of isoform CopA2 has no effect on Cu toxicity nor intracellular Cu levels but it leads to higher H2O2 sensitivity and reduced cytochrome oxidase activity
malfunction
-
mutation of CopA extracellular loops or the electropositive surface of CusF leads to a decrease in Cu+ transfer efficiency, while mutation of Met and Glu residues proposed to be part of the metal exit site in the ATPase yields enzymes with lower turnover rates, although Cu+ transfer is minimally affected
malfunction
-
a loss-of-function mutant line shows no apparent defect in in vivo blood stage growth. But parasite transmission through the mosquito vector is severely affected, although not entirely abolished. Male and female gametocytes are abundant in cutp? parasites, but activation of male microgametes and exflagellation are strongly impaired. This specific defect can be mimicked by addition of the copper chelator neocuproine to wild-type gametocytes. Female fertility is also severely abrogated. Targeted deletion of CuTP does not affect asexual blood stage growth in mice
malfunction
role of extracellular superoxide dismutase SOD3 and ATP7A in endothelial dysfunction in type 1 diabetes mellitus. Type 1 diabetes mellitus-induced endothelial dysfunction and decrease of SOD3 activity are rescued in transgenic mice overexpressing the enzyme ATP7A, a copper transporter. Copper transporter ATP7A protein expression is significantly reduced in blood vessels from type 1 diabetes mellitus mice in part due to the insulin deficiency but not high glucose. Transgenic mice overexpressing ATP7A restore type 1 diabetes mellitus-induced impaired SOD3 activity and endothelial function by reducing superoxide levels
malfunction
the loss of ATP7B activity is associated with Wilson disease, a severe hepato-neurological disorder
malfunction
addition of high Cu2+ concentrations reduce ATP7B incorporation into AP-1-containing clathrin-coated vesicles and cause loss of trans-Golgi network localization and somatodendritic polarity of ATP7B
malfunction
Menkes disease results from loss-of-function mutations in ATP7A
malfunction
Wilson's disease results from loss-of-function mutations in ATP7B. Loss of ATP7B function leads to excess Cu accumulation in the brain, kidney and particularly in the liver, owing to defective biliary Cu excretion across the apical surface of hepatocytes. Wilson's disease mutation affects the intracellular trafficking of ATP7B, while having little effect on ATPase activity itself, indicating that a mislocalization of ATP7B is sufficient to cause the disease
malfunction
copper deficiency causes Menkes disease in pediatric subjects with a phenotype underlying a X-linked recessive disorder of growth retardation, neurodegeneration, and peculiar hair. Mutations in the gene encoding the enzyme are implicated in at least two other distinctive phenotypes: occipital horn syndrome and ATP7A-related isolated distal motor neuropathy. Disorders caused by impaired ATP7A function and clinical phenotypes associated with disturbed copper metabolism involving hypotonia, seizures, developmental delay, brain atrophy, and coarse, lightly pigmented hair that rubs off easily, jowly facies, lax skin and joints, decreased bone density, bladder diverticula, gastric polyps, venous aneurysms, cardiac defects, vascular tortuousity, and blue irides, overview. The MEDNIK syndrome is caused by mutations in the s1A subunit of adaptor protein complex 1 (AP-1), which leads to detrimental effects on ATP7A trafficking
malfunction
enzyme missense mutations are involved in Menkes disease
malfunction
enzyme missense mutations are involved in Wilson's disease
malfunction
inactivation of ATP7A causes Menkes disease, a the severe neurological disorder
malfunction
disruption of ctpB in Mycobacterium tuberculosis cells do not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper
malfunction
mutations in gene encoding ATP7A causes a genetic disorder of Cu homeostasis, Menkes disease
malfunction
mutation in ATP7B gene causes Wilson disease that is characterized by severe hepatic and neurological symptoms
malfunction
yellow pigment accumulation in Aspergillus flavus mutant results from a defect in AFLA_051390
malfunction
mutation in ATP7B gene might disturb the structural conformation and catalytic function of the ATP7B protein may be inducing Wilson disease
malfunction
deletion of crpA or crpB alone did not alter high Cu tolerance, suggesting they are redundant. Deletion of both genes resulted in extreme Cu sensitivity that was greater than that following deletion of the regulatory transcription factor aceA. The DELTAcrpADELTAcrpB strains are also sensitive to ROI stress. Compared to wild type, these mutants are impaired in the ability to colonize maize seed treated with Cu fungicide but show no difference in virulence on non-treated seed
malfunction
mutations in gene encoding ATP7B causes a genetic disorder of Cu homeostasis, Wilson disease
malfunction
inactivation of ATP7B causes Wilson disease, a severe neurological disorder
malfunction
the disruption of ctpB in Mycobacterium tuberculosis cells does not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper
malfunction
-
role of extracellular superoxide dismutase SOD3 and ATP7A in endothelial dysfunction in type 1 diabetes mellitus. Type 1 diabetes mellitus-induced endothelial dysfunction and decrease of SOD3 activity are rescued in transgenic mice overexpressing the enzyme ATP7A, a copper transporter. Copper transporter ATP7A protein expression is significantly reduced in blood vessels from type 1 diabetes mellitus mice in part due to the insulin deficiency but not high glucose. Transgenic mice overexpressing ATP7A restore type 1 diabetes mellitus-induced impaired SOD3 activity and endothelial function by reducing superoxide levels
-
malfunction
-
a loss-of-function mutant line shows no apparent defect in in vivo blood stage growth. But parasite transmission through the mosquito vector is severely affected, although not entirely abolished. Male and female gametocytes are abundant in cutp? parasites, but activation of male microgametes and exflagellation are strongly impaired. This specific defect can be mimicked by addition of the copper chelator neocuproine to wild-type gametocytes. Female fertility is also severely abrogated. Targeted deletion of CuTP does not affect asexual blood stage growth in mice
-
malfunction
-
yellow pigment accumulation in Aspergillus flavus mutant results from a defect in AFLA_051390
-
malfunction
-
the disruption of ctpB in Mycobacterium tuberculosis cells does not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper
-
physiological function
couple the energy of ATP hydrolysis to heavy metal ion translocation across membranes
physiological function
-
Escherichia coli CopA is a copper ion-translocating P-type ATPase that confers copper resistance
physiological function
the constitutive expression of copTA probably provides a constant and low level supply of the protein CopT and the Cu+-exporting ATPase CopA that maintain homeostasis, allowing the cell to adjust to small fluctuations in copper levels under normal condition
physiological function
-
the Metallosphaera sedula copRTA locus conferrs copper resistance when expressed in Sulfolobus solfataricus. The level produced is more than 8fold less than the resistance level of wild-type Metallosphaera sedula (76 mM)
physiological function
-
ATP7B is a copper dependent P-type ATPase, required for copper homeostasis
physiological function
the enzyme is involved in transporting Cu+ throughout biological membranes
physiological function
the enzyme couples the hydrolysis of ATP to the efflux of cytoplasmic Cu+
physiological function
-
Isoforms CopA1 and CopA2 catalyse cytoplasmic Cu+ efflux into the periplasm. Isoforms CopA1 and CopA2 are essential for virulence. Isoform CopA1 maintains the cellular Cu quota and provides tolerance to this metal
physiological function
-
isoform CtrA2 presumably transports reduced Cu+, while isoform CtrA3 presumably transports the oxidized Cu+
physiological function
the P-type ATPase CopA plays a major role in the resistance of the cell to copper. The N-terminal domains of Cu(I)-transporting P-type ATPases interact with other domains of the transporter, thereby regulating transport activity
physiological function
-
mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones, specific transfer occurs after protein-protein recognition and interaction, requirement of multiple homologous transporters and chaperones for specificity in Cu+ delivery to alternative protein targets. Cellular copper homeostasis requires transmembrane transport and compartmental trafficking while maintaining the cell essentially free of uncomplexed Cu2+/+. In bacteria, soluble cytoplasmic and periplasmic chaperones bind and deliver Cu+ to target transporters or metalloenzymes. Transmembrane Cu+-ATPases couple the hydrolysis of ATP to the efflux of cytoplasmic Cu+. Cytosolic Cu+ chaperones (CopZ) interact with a structural platform in Cu+-ATPases (CopA) and deliver copper into the ion permeation path. CusF is a periplasmic Cu+ chaperone that supplies Cu+ to the CusCBA system for efflux to the extracellular milieu. Direct Cu+ transfer from the ATPase CopA to the periplasmic chaperone CusF requiring the specific interaction of the Cu+-bound form of CopA with apo-CusF for subsequent metal transfer upon ATP hydrolysis, the reverse Cu transfer from CusF to CopA is not observed
physiological function
CopA is an effective copper pump at low and high copper concentrations. The enzyme is not a strict prerequisite to the biosynthesis of the copper protein cytochrome oxidase. CopA and CopB act as resistance factors to copper ions at overlapping concentrations, both ATPases are involved in resistance to silver
physiological function
CopB is a low-affinity copper export ATPase, which is only relevant if the media copper concentration is exceedingly high. The enzyme is not a strict prerequisite to the biosynthesis of the copper protein cytochrome oxidase. CopA and CopB act as resistance factors to copper ions at overlapping concentrations, both ATPases are involved in resistance to silver
physiological function
-
the enzyme is involved in homeostasis of the trace element copper, that is essential to all eukaryotic life. Copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. A healthy copper homeostasis is critical to malaria parasite fertility of both genders of gametocyte and to transmission to the mosquito vector, Anopheles stephensi
physiological function
P1B-ATPases are among the most common resistance factors to metal-induced stress, they are capable of exporting transition metal ions at the expense of ATP hydrolysis. Copper binding to metal-binding domains appears non-essential, because no loss of function is observed when the ligand CxxC motifs are omitted
physiological function
the enzyme ATP7A plays a critical role in delivering cofactor copper to extracellular superoxide dismutase SOD3 for its full activation
physiological function
human Cu(I)-transporting ATPase ATP7B plays an essential role in maintaining cellular copper homeostasis. The enzyme transports copper to metalloenzymes undergoing functional maturation in this compartment. ATP hydrolysis supplies energy for copper transport. Upon copper elevation, enzyme ATP7B moves from the trans-Golgi network to specialized vesicles. In the vesicles, ATP7B sequesters excess copper for further export, which occurs via vesicle fusion at the plasma membrane. Following copper depletion, ATP7B returns from vesicles to the trans-Golgi network to resume its function in the biosynthesis of cuproenzymes. Role for domain dynamics in ATP7B trafficking
physiological function
the enzyme binds to the gamma-subunit of AP-1, an effector of polarized sorting in neurons, via dileucine-dependent binding of the C-terminal tail of ATP7B. Interaction with AP-1 is critical for somatodendritic polarity of ATP7B. Altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the sigma1A subunit isoform of AP-1
physiological function
cellular Cu homeostasis is highly regulated and is achieved in part by two intracellular Cu-transporting P-type ATPases, ATP7A and ATP7B. When Cu is low, the enzymes pump cytosolic Cu into the luminal spaces in the secretory pathway to supply Cu to newly synthesized cuproenzymes. When Cu is high, Cu ATPases exit the trans-Golgi network in vesicles and move near the plasma membrane, where they extrude Cu from the cell
physiological function
cellular Cu homeostasis is highly regulated and is achieved in part by two intracellular Cu-transporting P-type ATPases, ATP7A and ATP7B. When Cu is low, the enzymes pump cytosolic Cu into the luminal spaces in the secretory pathway to supply Cu to newly synthesized cuproenzymes. When Cu is high, Cu ATPases exit the trans-Golgi network in vesicles and move near the plasma membrane, where they extrude Cu from the cell. Cu induces an increase in the number of ATP7B vesicles, which traverse large basolateral endosomes en route to the apical domain
physiological function
enzyme ATP7A is a highly conserved ion-motive ATPase and a critical copper transport protein with multiple important cellular functions, e.g. role of ATP7A at the blood-brain and the blood-CSF barriers and the specific functions of the copper transporter in glutamatergic, acetylcholinergic, and other neurons
physiological function
transporter ATP7B maintains a Cu gradient along the duodenal crypt-villus axis and buffers Cu levels in the cytosol of enterocytes, mediated by rapid Cu-dependent enlargement of ATP7B-containing vesicles and increased levels of ATP7B. Intestines of Atp7b-/- mice show reduced Cu storage pools in intestine, Cu depletion, accumulation of triglyceride-filled vesicles in enterocytes, mislocalization of apolipoprotein B, and loss of chylomicrons
physiological function
in mice, in which the Atp7a gene is specifically deleted in cells of the myeloid lineage, including macrophages, primary macrophages isolated exhibit decreased copper transport into phagosomal compartments and a reduced ability to kill Salmonella enterica serovar Typhimurium compared to wild-type mice. The mutant mice are also more susceptible to systemic infection by Salmonella typhimurium than wild-type mice. Deletion of the Salmonella typhimurium copper exporters, CopA and GolT decreases infection in wild-type mice but not in the mutant mice
physiological function
deletion of the copper exporters, CopA and GolT decreases infection in wild-type mice but not in mice, in which the Atp7a transporter gen is specifically deleted in cells of the myeloid lineage
physiological function
deletion of isoform ATP7A in H-RAS transformed tumorigenic mouse embryonic markedly suppresses tumorigenesis relative to wild type parental cells, associated with hyperaccumulation of copper and sensitivity to reactive oxygen species and hypoxia. Tumor grafts lacking ATP7A are markedly more sensitive to cisplatin chemotherapy compared to ATP7A-expressing control tumors
physiological function
the CopA chaperone is expressed in Escherichia coli from the same gene that encodes the transporter. Some ribosomes translating CopA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 aa-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations. High efficiency of frameshifting is achieved by the combined stimulatory action of a slippery sequence, an mRNA pseudoknot, and the CopA nascent chain
physiological function
ATP7A interacts with IQGAP1, a Rac1 and receptor tyrosine kinase binding scaffolding protein. In cultured rat aortic smooth muscle cells, PDGF stimulation rapidly promotes ATP7A association with IQGAP1 and Rac1 and their translocation to the lipid rafts and leading edge. ATP7A directly binds to NH2-terminal domain of IQGAP1. Both ATP7A or IQGAP1 depletion using siRNA significantly inhibits PDGF-induced vascular smooth muscle cell migration without additive effects
physiological function
RNAi knockdown of the high-affinity copper importer CTR1 results in significant viral growth defects of the influenza A virus (7.3fold reduced titer at 24 hours post-infection). Knockdown of CTR1 or the trans-Golgi copper transporter ATP7A significantly reduces polymerase activity in a minigenome assay. Both copper transporters are required for authentic viral RNA synthesis and nucleoprotein and matrix (M1) protein accumulation in the infected cell
physiological function
conserved oligomeric Golgi (COG) null cells possess altered content and subcellular localization of ATP7A and CTR1 (SLC31A1), the transporter required for copper uptake, as well as decreased total cellular copper, and impaired copper-dependent metabolic responses
physiological function
ATP7A interacts with hundreds of proteins present in different compartments within cells
physiological function
-
changes in the expression of ATP7A and conserved oligomeric Golgi subunits in Drosophila melanogaster neurons alter synapse development in larvae and copper-induced mortality of adult flies
physiological function
the N-terminus of CTR1 may serve as intermediate binding site during Cu(II) transfer from blood copper carriers to the transporter. Human N-terminal sequence Met-Asp-His, MDH-amide, but not MNH-amide forms a low abundance complex with non-amino terminal Cu(II)- and Ni(II)-binding site coordination involving the Met amine, His imidazole and Asp carboxylate. This species might assist Cu(II) relay down the peptide chain or its reduction to Cu(I), both necessary for the CTR1 function
physiological function
-
loss of COPT1 function results in a Cu-mitigated reduction of biomass production when the plant obtains its nitrogen exclusively from symbiotic nitrogen fixation. Mutation of COPT1 results in diminished nitrogenase activity in nodules. Expression of COPT1 in Saccharomyces cerevisiae complements the lack of yeast CTR1 gene
physiological function
Fe uptake and efflux are impaired by Atp7a silencing. Expression of the iron importer Dmt1, apical membrane ferrireductase Dcytb and iron exporter Fpn1 are decreased in Atp7a knockdown cells. Cell-surface ferrireductase activity increases about 5fold in Atp7a knockdown cells despite decreased Dcytb mRNA expression. Increased expression of iron oxidase hephaestin is associated with increased ferroxidase activity in knockdown cells
physiological function
Fe uptake and efflux are impaired by Atp7a silencing
physiological function
ATP7A protein is markedly downregulated in vessels isolated from high-fat diet-induced or db/db type 2 diabetes mellitus mice. Downregulation of ATP7A in type 2 diabetes mellitus mice vessels is restored by constitutive active Akt or in protein-tyrosine phosphatase 1B-deficient type 2 diabetes mellitus mice. Insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at residues Ser1424/1463/1466. Superoxide dismutase SOD3 activity is reduced in Akt2-/- vessels or vascular smooth muscle cells, which is rescued by ATP7A overexpression
physiological function
the enzyme is essential for the normal function of the mammalian central nervous system. It is involved in Cu delivery to Cu-dependent enzymes within the secretory pathway and maintenance of Cu homeostasis in tissues
physiological function
the enzyme is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification
physiological function
the copper efflux transporters ATP7A and ATP7B play an important role in platinum resistance
physiological function
the enzyme is able to transport Cu from the cytosol across membranes using ATP hydrolysis
physiological function
ATP7A plays a key role in the activation of LOX proteins whose activities promote tumor progression and metastasis. Higher levels of ATP7A correlate with a reduced survival rate of patients with breast cancer
physiological function
the enzyme transports copper to copper-dependent enzymes and traffics in apically targeted vesicles upon intracellular copper elevation
physiological function
the enzyme plays a crucial role in cellular copper homeostasis
physiological function
the enzyme is crucial for maintaining Cu homeostasis. The efficient hepatobiliary excretion of CuS nanoparticles is attributed to the participation of Cu-transporting ATPase ATP7B. Due to slow release of Cu ions from the endocytosed CuS nanoparticles, ATP7B traverses the endolysosomal compartment to chelate intravesicular Cu, regulating both ionic and particulate Cu excretion into bile canaliculi
physiological function
the enzyme is involved in biosynthesis of Aspergillus flavus conidial pigment
physiological function
the enzyme plays an important role in platinum drug resistance and cancer progression
physiological function
dopamine is converted to norepinephrine by dopamine-beta-hydroxylase, which acquires its essential Cu cofactor from ATP7A. Down-regulation of ATP7A, overexpression of ATP7B, and pharmacological Cu depletion increase dopamine-beta-hydroxylase retention in cells. ATP7B inactivation elevates extracellular DBH
physiological function
two copies of the Cu exporter P1-type ATPase in Aspergillus flavus, lead to a greater tolerance of Cu in this species than other Aspergilli. Both crpA and crpB are transcriptionally regulated by the Cu-fist TF AceA and both need to be deleted to detect sensitivity to Cu or ROI species
physiological function
the Lotus COPT proteins function in copper uptake. The fact that environmental conditions affect the expression of certain COPT genes supports their involvement in adaptive mechanisms
physiological function
the enzyme binds Cu(II) ions that are present in the blood. It reduces the Cu(II) ions to Cu(I) and it subsequently transfers Cu(I) to the cytoplasmic domain, where the ion is delivered to various cellular pathways
physiological function
accumulation of Pt in membrane vesicles requires ATP7B and its ATPase activity
physiological function
-
zAtp7b, but not zAtp7a, is responsible for Cu export in ZFL cells
physiological function
the enzyme is essential for the normal function of the mammalian central nervous system. Dopamine-beta-hydroxylase (DBH) acquires its essential Cu cofactor from ATP7A. It is involved in Cu delivery to Cu-dependent enzymes within the secretory pathway and maintenance of Cu homeostasis in tissues
physiological function
the enzyme induces mycobacterial tolerance to toxic concentrations of Cu2+
physiological function
-
the enzyme plays a key role in cellular copper homeostasis and acts as a Cu+ transporter
physiological function
the enzyme supports the detoxification of Ag and Cu, which is, besides efficient transport, the prerequisite for (hyper)accumulation
physiological function
the enzyme is involved in the delivery of physiological Cu into organelles of endomembrane system for the biosynthesis of Cu-dependent proteins
physiological function
-
the P-type ATPase CopA plays a major role in the resistance of the cell to copper. The N-terminal domains of Cu(I)-transporting P-type ATPases interact with other domains of the transporter, thereby regulating transport activity
-
physiological function
-
the enzyme ATP7A plays a critical role in delivering cofactor copper to extracellular superoxide dismutase SOD3 for its full activation
-
physiological function
-
the enzyme is involved in homeostasis of the trace element copper, that is essential to all eukaryotic life. Copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. A healthy copper homeostasis is critical to malaria parasite fertility of both genders of gametocyte and to transmission to the mosquito vector, Anopheles stephensi
-
physiological function
-
deletion of the copper exporters, CopA and GolT decreases infection in wild-type mice but not in mice, in which the Atp7a transporter gen is specifically deleted in cells of the myeloid lineage
-
physiological function
-
the constitutive expression of copTA probably provides a constant and low level supply of the protein CopT and the Cu+-exporting ATPase CopA that maintain homeostasis, allowing the cell to adjust to small fluctuations in copper levels under normal condition
-
physiological function
Saccharolobus solfataricus PBL2025
-
CopA is an effective copper pump at low and high copper concentrations. The enzyme is not a strict prerequisite to the biosynthesis of the copper protein cytochrome oxidase. CopA and CopB act as resistance factors to copper ions at overlapping concentrations, both ATPases are involved in resistance to silver
-
physiological function
Saccharolobus solfataricus PBL2025
-
CopB is a low-affinity copper export ATPase, which is only relevant if the media copper concentration is exceedingly high. The enzyme is not a strict prerequisite to the biosynthesis of the copper protein cytochrome oxidase. CopA and CopB act as resistance factors to copper ions at overlapping concentrations, both ATPases are involved in resistance to silver
-
physiological function
-
the enzyme is involved in biosynthesis of Aspergillus flavus conidial pigment
-
physiological function
-
the enzyme induces mycobacterial tolerance to toxic concentrations of Cu2+
-
additional information
the enzyme CopA contains two N-terminal soluble domains, CopAa and CopAb, connected by a short linker, both domains are able to bind Cu(I) extremely tightly. Isolated N-terminal soluble domains CopAa and CopAb bind Cu(I) with an extremely high affinity and remain as a monomers up to a level of 1 Cu(I) per protein. Above this level, they undergo dimerization. The Cu(I)-binding properties of CopAb are very similar to those of the two-domain protein CopAab, indicating that this domain plays a dominant role in determining the binding properties of CopAab. The MTCAAC Cu(I)-binding motif of each domain is located at opposite ends of the protein molecule, ruling out the possibility of intra protein, inter-domain Cu(I)-binding, proposed model of Cu(I)-binding to CopAb and the resulting association state changes, overview. CopAb in isolation does not undergo Cu(I)-mediated unfolding, the unfolding of CopAab at high levels of Cu(I) is due to the instability of the CopAa domain and the remaining secondary structure observed at high Cu(I) levels in CopAab is due to the stable CopAb domain
additional information
-
the enzyme CopA contains two N-terminal soluble domains, CopAa and CopAb, connected by a short linker, both domains are able to bind Cu(I) extremely tightly. Isolated N-terminal soluble domains CopAa and CopAb bind Cu(I) with an extremely high affinity and remain as a monomers up to a level of 1 Cu(I) per protein. Above this level, they undergo dimerization. The Cu(I)-binding properties of CopAb are very similar to those of the two-domain protein CopAab, indicating that this domain plays a dominant role in determining the binding properties of CopAab. The MTCAAC Cu(I)-binding motif of each domain is located at opposite ends of the protein molecule, ruling out the possibility of intra protein, inter-domain Cu(I)-binding, proposed model of Cu(I)-binding to CopAb and the resulting association state changes, overview. CopAb in isolation does not undergo Cu(I)-mediated unfolding, the unfolding of CopAab at high levels of Cu(I) is due to the instability of the CopAa domain and the remaining secondary structure observed at high Cu(I) levels in CopAab is due to the stable CopAb domain
additional information
-
homology modeling of EcCopA, docking of the apo-EcCusF, PDB ID 1ZEQ, or the holo-EcCusF, PDB ID 2VB2, structures with the extracellular periplasmic loops of the ATPase
additional information
roles of the two adjacent metal-binding domains of CopA: the distal N-terminal metal-binding domain possesses a function analogous to the metallochaperones of related prokaryotic copper resistance systems, that is its involvement in the copper transfer to the membrane integral ion-binding sites of CopA. In contrast, the proximal domain metal-binding domain has a regulatory role by suppressing the catalytic activity of CopA in absence of copper
additional information
-
roles of the two adjacent metal-binding domains of CopA: the distal N-terminal metal-binding domain possesses a function analogous to the metallochaperones of related prokaryotic copper resistance systems, that is its involvement in the copper transfer to the membrane integral ion-binding sites of CopA. In contrast, the proximal domain metal-binding domain has a regulatory role by suppressing the catalytic activity of CopA in absence of copper
additional information
identification of spatial organization of N-terminal enzyme domain of ATP7B and transient functionally relevant interactions between metal-binding domains 1-3, modulation of these interactions by nanobodies in cells enhances relocalization of the endogenous enzyme toward the plasma membrane linking molecular and cellular dynamics of the transporter. Stimulation of enzyme trafficking by nanobodies in the absence of elevated copper provides direct evidence for the important role of the N-terminal enzyme domains structural dynamics in regulation of enzyme localization in a cell
additional information
Cu-directed trans-Golgi network-to-apical trafficking occurs via a basolateral compartment in hepatocytes in vivo
additional information
Cu-directed trans-Golgi network-to-apical trafficking occurs via a basolateral compartment in hepatocytes in vivo
additional information
the enzyme shows six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices, the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, the heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition. Homology structure modeling based on the existing structure of the soluble domain and the structure of the homologous LpCopA from the bacterium Legionella pneumophila. The domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved
additional information
the enzyme shows six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices, the heavy-metal binding domains, HMBD5 and HMBD6 are the most crucial for function, the heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition. Homology structure modeling based on the existing structure of the soluble domain and the structure of the homologous LpCopA from the bacterium Legionella pneumophila. The domains and residues involved in the catalytic phosphorylation events and copper transfer are highly conserved
additional information
-
the enzyme CopA contains two N-terminal soluble domains, CopAa and CopAb, connected by a short linker, both domains are able to bind Cu(I) extremely tightly. Isolated N-terminal soluble domains CopAa and CopAb bind Cu(I) with an extremely high affinity and remain as a monomers up to a level of 1 Cu(I) per protein. Above this level, they undergo dimerization. The Cu(I)-binding properties of CopAb are very similar to those of the two-domain protein CopAab, indicating that this domain plays a dominant role in determining the binding properties of CopAab. The MTCAAC Cu(I)-binding motif of each domain is located at opposite ends of the protein molecule, ruling out the possibility of intra protein, inter-domain Cu(I)-binding, proposed model of Cu(I)-binding to CopAb and the resulting association state changes, overview. CopAb in isolation does not undergo Cu(I)-mediated unfolding, the unfolding of CopAab at high levels of Cu(I) is due to the instability of the CopAa domain and the remaining secondary structure observed at high Cu(I) levels in CopAab is due to the stable CopAb domain
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
240000
and 480000, PAGE and gel filtration, streptavidin-tagged recombinant protein
480000
and 240000, PAGE and gel filtration, streptavidin-tagged recombinant protein
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
and monomer, 2 * 230000, streptavidin-tagged recombinant protein, calculated from sequence
monomer
and dimer, 1 * 230000, streptavidin-tagged recombinant protein, calculated from sequence
?
x * 8256.44, recombinant N-terminal domain CopAb, mass spectrometry, x * 8258.17, N-terminal domain CopAb, sequence calculation
?
-
x * 8256.44, recombinant N-terminal domain CopAb, mass spectrometry, x * 8258.17, N-terminal domain CopAb, sequence calculation
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop method, crystal structure of the apo, oxidized C-terminal-metal binding domain to 2.0 A resolution. In the structure, two C-terminal-metal binding domain monomers form a domain-swapped dimer
wild-type and selenomethionine CopA-ATP binding domain, hanging drop vapor diffusion method, using 100 mM sodium acetate, pH 4.6, 58% polyethylene glycol 4000, and 1020% glycerol
with bound adenosine 5'-[beta, gamma-methylene]triphosphate or ADP and Mg2+, vapor diffusion method, using 5% (w/v) PEG 6000, 1.25-1.5M NaCl and 100 mM MES, pH 5.5-5.75, at 10°C
structure determination of the 73-147 domain in the 1-151 construct, in the apo state through 1H, 15N and 13C NMR spectroscopies, the structure of the Cu(I)-loaded 73-147 domain has been also determined in the construct 73-151
NMR structure of metal-binding domain MBD1, shows the characteristic beta,alpha,beta,beta,alpha,beta ferredoxin fold. The copper binding motif CxxC appears to experience complex dynamics
structural model of a deletion mutant lacking the four N-terminal metal-binding domains
structural modeling. The ion-entry path involves one transient Met148-Cys382 ion-binding site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The protein anchors predominantly in the cytoplasmic leaflet with exposed positive charges on the putative MB docking platform
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D555A
AsCCC2D555A cells show full growth on the YPEG medium supplemented with 1 mM Cu2+
C27A/C30A
replacement of Cys in the N-terminal metal binding domain, mutation leads to about 40% reduction in Ag+ activated ATPase activity and about 60% reduction in Cu+-activated ATPase activity. The mutant enzyme binds Cu+, Ag+, and ATP with the same high apparent affinities as the wild-type enzyme. Evidence that the N-terminal metal binding domain disruption has no effect on the E1-E2 equilibrium is provided by the normal interaction of ATP acting with low affinity and the unaffected IC50 for vanadate inhibition observed in the C27A/C30A-substituted enzyme
C27A/C30A/C751A/C754A
mutation leads to about 40% reduction in Ag+ activated ATPase activity and about 60% reduction in Cu+-activated ATPase activity
C380A/C382A
the mutant enzyme binds ATP, indicating its correct folding and suggesting that enzyme turnover is prevented by the lack of metal binding to the transmembrane site
C751A/C754A
the mutant enzyme has no significant effect on ATPase activity, enzyme phosphorylation, apparent binding affinities of ligands, or E1-E2 equilibrium
D336A
D336C
E205A
E205C
H462Q
the mutation reduces the affinity for adenosine 5'-[beta, gamma-methylene]triphosphate about 20fold
I685E
-
Cu+/ATPase activity is about 50% of the activity of the wild-type enzyme
I685T
-
Cu+/ATPase activity is about 25% of the activity of the wild-type enzyme
K145A/S149A/R152A/R153A/R154A
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
L686A
-
Cu+/ATPase activity is about 80% of the activity of the wild-type enzyme
M158A
M158C
M711A
P688A
-
Cu+/ATPase activity is about 70% of the activity of the wild-type enzyme
P704A
-
Cu+/ATPase activity is about 75% of the activity of the wild-type enzyme
S139A/G140A
S714A
-
Cu+/ATPase activity is about 30% of the activity of the wild-type enzyme
S714R
-
Cu+/ATPase activity is about 65% of the activity of the wild-type enzyme
S715A
Y682A
Y682S
-
Cu+/ATPase activity is about 10% of the activity of the wild-type enzyme
C14S/C17S
site-directed mutagenesis, a dysfunctional non-copper-binding mutant
A874V
partial targeting of the mutant enzyme to trans-Golgi Network and post-Golgi vesicles and slightly lower copper transport activity than wild-type enzyme
C575A/C578A
-
mutation in the 6th copper site of the NMBD, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
C983A/C985A
G591D
mutant shows subapical localization and trans-Golgi Network localization
G85V
G875R
retention of mutant enzyme in the endoplasmic reticulum, no copper transport activity
H1069Q
mutation causes a milder form of Wilson disease. The mutant enzyme displays impaired targeting
L1373P
mutant enzyme is arrested at endoplasmic reticulum, no copper transport activity
L1373R
mutant enzyme is arrested at endoplasmic reticulum, no copper transport activity
L168P
mutant shows subapical localization and trans-Golgi Network localization
L492S
mislocalization of the mutant at the basolateral region and lower copper transport activity than wild-type enzyme
L795F
partial targeting of the mutant enzyme to trans-Golgi Network and post-Golgi vesicles
R778L
mutation causes early onset and aggressive form of Wilson disease. The mutant enzyme resides in endoplasmic reticulum and trans-Golgi Network
R969Q
the mutant enzyme is exclusively localized in the endoplasmic reticulum, no copper transport activity
S1423N
mutant enzyme shows trans-Golgi Network localization and lower copper transport activity than wild-type enzyme
T994I
-
mutation is located in the sixth transmembrane domain of ATP7A, and is associated with the an adult-onset isolated distal motor neuropathy, and with an abnormal interaction with p97/valosin-containing protein. T994I substitution results in conformational exposure of the UBX domain in the third lumenal loop of ATP7A, which then binds the N-terminal domain of p97/VCP. This abnormal interaction occurs at or near the cell plasma membrane
K135E/R136E
almost complete loss of activity
K135S/K142S
almost complete loss of activity
H479Q
-
the mutant is unable to utilize ATP, whereas phosphorylation by phosphate is retained
additional information
D336A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
D336A
the mutant shows increased Vmax value compared to the wild type enzyme
D336A
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
D336C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
D336C
the mutant shows increased Vmax value compared to the wild type enzyme
D336C
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
E205A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
E205A
the mutant shows increased Vmax value compared to the wild type enzyme
E205A
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
E205C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
E205C
the mutant shows increased Vmax value compared to the wild type enzyme
E205C
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
M158A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
M158A
the mutant shows reduced Vmax value compared to the wild type enzyme
M158A
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
M158C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
M158C
the mutant shows increased Vmax value compared to the wild type enzyme
M158C
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
S139A/G140A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant enzyme
S139A/G140A
the mutant shows increased Vmax value compared to the wild type enzyme
S139A/G140A
mutation does not affect the ATPase activity when stimulated by free Cu+ in the assay media, nor does the mutation impair Cu+ binding to transmembrane metal-binding site
C983A/C985A
-
mutation in the transmembrane copper binding site, TMBS, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
G85V
mutation involved in Wilson disease. Mutation causes disruption of the structure of metal-binding domain MBD1
G85V
mutant shows subapical localization and trans-Golgi Network localization and slightly lower copper transport activity than wild-type enzyme
additional information
-
Tyr682, Asn683, Met711 and Ser715 are identified as required for Cu+ binding. Replacement of these residues abolishes enzyme activity. These mutant proteins do not undergo Cu+-dependent phosphorylation by ATP but are phosphorylated by inorganic phosphate in the absence of Cu+
additional information
-
interaction analysis of recombinant wild-type and mutant enzymes CopA and chaperones CusF, overview
additional information
construction of several truncation mutants of the metal-binding domains of CopA enzyme. Complementation of copA-deficient Escherichia coli strain DC194 by homologous expression of the wild-type and mutant enzymes to different extents and growth monitoring in copper-supplemented media, overview
additional information
-
construction of several truncation mutants of the metal-binding domains of CopA enzyme. Complementation of copA-deficient Escherichia coli strain DC194 by homologous expression of the wild-type and mutant enzymes to different extents and growth monitoring in copper-supplemented media, overview
additional information
deletion of the four N-terminal metal-binding domains does not disrupt dimerization. Unlike the full-length ATP7B, the truncated protein is targeted primarily to vesicles
additional information
the presence of the most N-terminal metal-binding domain increases overall ATP7B-mediated Cu transport activity, whereas presence of the third metal-binding domain decreases the activity. Upon removal of all metal-binding domains in ATP7B, the ability to transport Cu disappears
additional information
-
generation of a Plasmodium berghei loss-of-function mutant line, phenotype, detailed overview
additional information
-
generation of a Plasmodium berghei loss-of-function mutant line, phenotype, detailed overview
-
additional information
-
disruption of gene copA via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
additional information
disruption of gene copA via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
additional information
-
disruption of gene copB via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
additional information
disruption of gene copB via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
additional information
Saccharolobus solfataricus PBL2025
-
disruption of gene copA via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
-
additional information
Saccharolobus solfataricus PBL2025
-
disruption of gene copB via allelic replacement does not affect the sensitivity of Sulfolobus solfataricus to reactive oxygen species
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
66 - 85
incubation of CopA in the absence of substrates at temperatures in the 6685°C range leads to an irreversible exponential decrease in enzyme activity suggesting a two-state process involving fully-active and inactive molecules. Although CopA inactivated much slower than mesophilic proteins, the activation energy is similar to that observed for mesophilic P-type ATPases. The inactivation process is found to be associated with the irreversible partial unfolding of the polypeptide chain. However, the inactive thermally denatured protein still conserves large hydrophobic regions and considerable secondary structure
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
guanidine-HCl
the incubation of the enzyme reconstituted in phospholipid/detergent mixed micelles with high concentrations of guanidinium hydrochloride at 25°C induces a reversible decrease in fluorescence quantum yield, far-UV ellipticity, and loss of ATPase and phosphatase activities. Refolding of the enzyme from this unfolded state leads to recovery of full biological activity and all the structural features of the native enzyme. The unfolding shows typical characteristics of a two-state process. Most of the secondary and tertiary structures are disrupted. The fraction of Trp fluorescence accessible to soluble quenchers shifts from 0.52 in the native state to 0.96 in the unfolded state, with a significant spectral redshift. Hydrophobic patches in the enzyme, mainly located in the transmembrane region, are disrupted as indicated by 1-anilino-naphtalene-8-sulfonate fluorescence. Nevertheless, the unfolded state has a small but detectable amount of residual structure, which might play a key role in both CopA folding and adaptation for working at high temperatures
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Co2+ metal affinity resin column chromatography, and gel filtration
CopA purified from dodecylmaltoside-solubilized membranes by metal chelate affinity chromatography, presence of a small amount of copper during solubilization and purification found to result in a more active and stable CopA
-
Enterococcus hirae mutant Yl lacks the CopY repressor and overexpresses the cop operon of about 50-fold is used for CopB purification
full-length StCopB (WT-StCopB,residues 1-785) and StCopB lacking the N-terminal region (DELTAMBD-StCopB, residues 114-785)
-
gene copAab, recombinant full-length enzyme and N-terminal domains CopAa and CopAb from Escherichia coli strain BL21(DE3) by anion exchange chromatography, ultrafiltration, and gel filtration
in eukaryotic cells, human ATP7B forms dimers that can be purified following solubilization
Ni Sepharose 6 column chromatography and Superdex 75 gel filtration
recombinant His-tagged MBP-fusion enzyme from Escherichia coli by nickel affinity chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
CopA cDNA lacking the N-terminal metal binding domain and the C-terminal metal-binding domain coding regions is ligated into pEXP-NT vector, which adds an N terminus His6 tag sequence is used as a template to introduce the mutations coding for the single substitutions M158A, M158C, E205A, E205C, D336A, and D336C, and the multiple replacements S139A/G140A and K145A/S149A/R152A/R153A/R154A
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
expression in Escherichia coli. The use of DNA synthesis to generate silent mutations across the majority of both mouse and human ATP7A open reading frames is sufficient to stabilize the genes in high-copy plasmids
expression in Saccharomyces cerevisiae
gene copA lacking the N-metal-binding-domain-coding regions, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)lambda
-
gene copA, phylogenetic analysis and sequence comparisons, recombinant expression of Sulfolobus solfataricus CopA in Escherichia coli strain DC194, deficient in the PIB-type copper export ATPase copA, yielding poor or partial complementation
gene copAab, expression of full-length enzyme and N-terminal domains CopAa and CopAb in Escherichia coli strain BL21(DE3)
gene copB, phylogenetic analysis and sequence comparisons, recombinant expression of Sulfolobus solfataricus CopB in Escherichia coli strain DC194, deficient in the PIB-type copper export ATPase copA, yielding poor or partial complementation
gene Tgcutp or TGGT1_020170, recombinant expression of the Myc2-tagged enzyme in Toxoplasma gondii
-
heterologous functional complementation assay of the Saccharomyces cerevisiae ctr1DELTActr3DELTA strain, which lacks the corresponding yeast copper transporters, with the putative Lotus COPT proteins shows a partial rescue of the yeast phenotypes in restrictive media
microsomes derived from COS-1 cells infected with adenovirus vector and expressing recombinant ATP7A/B
-
Recombinant adenovirus vector, rAdATP7Bmyc, containing CMV promoter driven WT human ATP7B cDNA, fused with 30 cmyc tag, expression in COS-1 cells
-
recombinant expression in rat intestinal epithelial IEC-6 cells, Atp7a protein expression is induced more strongly than mRNA in the duodenum of iron-deprived rats, real-time quantitative RT-PCR enzyme expression analysis
recombinant expression of His-tagged MBP-fusion enzyme in Escherichia coli, overexpression of GFP-tagged ATP7B in Rattus norvegicus hippocampal neurons, co-expression with myc-tagged wild-type or V98S-mutant sigma1A, with HA-tagged wild-type or V98S-mutant sigma1B, and with HA-tagged wild-type or V98S-mutant sigma1C
recombinant expression of the N-terminal domain of human ATP7B (N-ATP7B) fused to maltose-binding protein, and FLAG-tagged enzyme in HEK293T-Rex cells, co-expression of GFP-tagged nanoparticle in HEK-293T cells, the nanobodies bind to the distinct regions of N-ATP7B, binding sites of 2R50 and 2R51 are located within metal binding domains MBD1-4, revealing transient inter-domain interactions in N-ATP7B
the N-terminal region of BsCopA contains two domains constituted by amino acid residues 1 to 72 and 73 to 147, which are expressed both separately and together, in both cases only the 73-147 domain is folded and is stable both in the copper(I)-free and in the copper(I)-bound forms
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
an increase in the external copper concentration induces the enzyme
Atp7a expression is upregulated by iron chelation and copper loading. Recombinant Atp7a protein expression is induced more strongly than mRNA in the duodenum of iron-deprived rats, Atp7a expression is upregulated by iron chelation and copper loading, iron chelation increases Atp7a mRNA expression by 1.6fold, but has little effect on protein levels
copper has a direct influence on Atp7a protein expression independent of changes in mRNA levels
copper transporter ATP7A protein expression is significantly reduced in blood vessels from type 1 diabetes mellitus mice
COPT1 gene expression is up-regulated 6 times by partial submergence treatment
COPT3 gene expression is up-regulated 3 times by partial submergence treatment
ctpB gene transcription is activated in cells under culture conditions that mimick the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper
expression of zatp7a is induced by Cu at 4 h and returns to the basal level by 24 h. Expression of zatp7a is induced by Zn at 4 h
-
expressions of zatp7b is induced by Cu at 4 h and returns to the basal level by 24 h
-
insulin treatment, but not high glucose, increases enzyme ATP7A expression in vascular smooth muscles cells
Sulfolobus responds to exposure to a sublethal copper excess by the transient active transcription of the copA gene. The copA transcript reaches a peak 1 h after treatment, corresponding to approximately 35fold the uninduced level. Thereafter, the transcript level decreases until a steady-state level of 2-3fold induction is reached in the following 16 h. In cells cultured for several generations in the presence of 0.75 mM copper, the amount of copA transcript is maintained at 2-3fold the uninduced level, indicating that its rate of expression is maintained constant during longterm exposures, provided the concentration of copper do not change
the copA gene is expressed at basal levels in untreated cells of both strain PBL2025 and strain PBL2050. After copper stress, the level of copA transcript increases approximately 30fold. The gene Sso2652 (copR) of the Sulfolobus solfataricus genome encodes a transcriptional activator of the copper-transporting ATPase CopA gene. The CopR protein is a copper-responsive regulators
the ctpB gene is transcriptionally activated under culture conditions that mimick the stress conditions similar to the intraphagosomal environment, but not under high doses of copper
transcriptionally induced by increasing Cu concentrations via activity of the Cu-fist DNA binding protein AceA
an increase in the external copper concentration induces the enzyme
an increase in the external copper concentration induces the enzyme
Saccharolobus solfataricus PBL2025
-
-
copper transporter ATP7A protein expression is significantly reduced in blood vessels from type 1 diabetes mellitus mice
copper transporter ATP7A protein expression is significantly reduced in blood vessels from type 1 diabetes mellitus mice
-
-
ctpB gene transcription is activated in cells under culture conditions that mimick the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper
ctpB gene transcription is activated in cells under culture conditions that mimick the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper
-
-
insulin treatment, but not high glucose, increases enzyme ATP7A expression in vascular smooth muscles cells
insulin treatment, but not high glucose, increases enzyme ATP7A expression in vascular smooth muscles cells
-
-
Sulfolobus responds to exposure to a sublethal copper excess by the transient active transcription of the copA gene. The copA transcript reaches a peak 1 h after treatment, corresponding to approximately 35fold the uninduced level. Thereafter, the transcript level decreases until a steady-state level of 2-3fold induction is reached in the following 16 h. In cells cultured for several generations in the presence of 0.75 mM copper, the amount of copA transcript is maintained at 2-3fold the uninduced level, indicating that its rate of expression is maintained constant during longterm exposures, provided the concentration of copper do not change
Sulfolobus responds to exposure to a sublethal copper excess by the transient active transcription of the copA gene. The copA transcript reaches a peak 1 h after treatment, corresponding to approximately 35fold the uninduced level. Thereafter, the transcript level decreases until a steady-state level of 2-3fold induction is reached in the following 16 h. In cells cultured for several generations in the presence of 0.75 mM copper, the amount of copA transcript is maintained at 2-3fold the uninduced level, indicating that its rate of expression is maintained constant during longterm exposures, provided the concentration of copper do not change
-
-
the copA gene is expressed at basal levels in untreated cells of both strain PBL2025 and strain PBL2050. After copper stress, the level of copA transcript increases approximately 30fold. The gene Sso2652 (copR) of the Sulfolobus solfataricus genome encodes a transcriptional activator of the copper-transporting ATPase CopA gene. The CopR protein is a copper-responsive regulators
the copA gene is expressed at basal levels in untreated cells of both strain PBL2025 and strain PBL2050. After copper stress, the level of copA transcript increases approximately 30fold. The gene Sso2652 (copR) of the Sulfolobus solfataricus genome encodes a transcriptional activator of the copper-transporting ATPase CopA gene. The CopR protein is a copper-responsive regulators
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
the fact that environmental conditions affect the expression of certain COPT genes supports their involvement in adaptive mechanisms and envisages putative biotechnological strategies to improve cattle copper nutrition
analysis
method to probe Cu flow through human Atox1 and copper chaperone ATP7B proteins when expressed in yeast.
diagnostics
the enzyme may be used as potential biomarker to predict the sensitivity of platinum-based chemotherapy in numerous malignancies
medicine
medicine
-
mutation T994I is located in the sixth transmembrane domain of ATP7A, and is associated with the an adult-onset isolated distal motor neuropathy, and with an abnormal interaction with p97/valosin-containing protein. T994I substitution results in conformational exposure of the UBX domain in the third lumenal loop of ATP7A, which then binds the N-terminal domain of p97/VCP. This abnormal interaction occurs at or near the cell plasma membrane
medicine
deletion of isoform ATP7A in H-RAS transformed tumorigenic mouse embryonic markedly suppresses tumorigenesis relative to wild type parental cells, associated with hyperaccumulation of copper and sensitivity to reactive oxygen species and hypoxia. Tumor grafts lacking ATP7A are markedly more sensitive to cisplatin chemotherapy compared to ATP7A-expressing control tumors
medicine
-
cisplatin-resistant cell sublines show cross-resistance to carboplatin and oxaliplatin. ATP7A expression in cisplatin-resistant cell sublines is much higher than in cisplatin-sensitive cell lines at both mRNA and protein levels. ATP7A-targeted siRNA in cisplatin-resistant cancer cells partially reverses cisplatin-resistance. It also increases cell apoptosis at different cisplatin concentrations
medicine
ATP7A protein is markedly downregulated in vessels isolated from type 2 diabetes mellitus patients. Akt2 (protein kinase B beta) activated by insulin promotes ATP7A stabilization via preventing ubiquitination/degradation as well as translocation to plasma membrane in vascular smooth muscle cells
medicine
ATP7A protein is markedly downregulated in vessels isolated from high-fat diet-induced or db/db type 2 diabetes mellitus mice. Downregulation of ATP7A in type 2 diabetes mellitus mice vessels is restored by constitutive active Akt or in protein-tyrosine phosphatase 1B-deficient type 2 diabetes mellitus mice. Insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at residues Ser1424/1463/1466. Superoxide dismutase SOD3 activity is reduced in Akt2-/- vessels or vascular smooth muscle cells, which is rescued by ATP7A overexpression
medicine
metallic gold nanoparticles have great potential for a wide variety of biomedical applications. Yet, slow clearance of Au nanoparticles significantly hinders their clinical translation. Copper sulfide facilitates hepatobiliary clearance of gold nanoparticles through the copper-transporting ATPase ATP7B. The CuS-Au conjugation approach provides a feasible strategy to enhance the hepatobiliary clearance of Au nanoparticles that may be applicable to various structures
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fan, B.; Rosen, B.P.
Biochemical characterization of CopA, the Escherichia coli Cu(I)-translocating P-type ATPase
J. Biol. Chem.
277
46987-46992
2002
Escherichia coli
brenda
Mandal, A.K.; Cheung, W.D.; Arguello, J.M.
Characterization of a thermophilic P-type Ag+/Cu+-ATPase from the extremophile Archaeoglobus fulgidus
J. Biol. Chem.
277
7201-7208
2002
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Sazinsky, M.H.; Mandal, A.K.; Argueello, J.M.; Rosenzweig, A.C.
Structure of the ATP binding domain from the Archaeoglobus fulgidus Cu+-ATPase
J. Biol. Chem.
281
11161-11166
2006
Archaeoglobus fulgidus (O29777)
brenda
Hatori, Y.; Majima, E.; Tsuda, T.; Toyoshima, C.
Domain organization and movements in heavy metal ion pumps: papain digestion of CopA, a Cu+-transporting ATPase
J. Biol. Chem.
282
25213-25221
2007
Thermotoga maritima (Q9WYF3), Thermotoga maritima
brenda
Chintalapati, S.; Al Kurdi, R.; van Scheltinga, A.C.; Kuehlbrandt, W.
Membrane structure of CtrA3, a copper-transporting P-type-ATPase from Aquifex aeolicus
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378
581-595
2008
Aquifex aeolicus
brenda
Hatori, Y.; Hirata, A.; Toyoshima, C.; Lewis, D.; Pilankatta, R.; Inesi, G.
Intermediate phosphorylation reactions in the mechanism of ATP utilization by the copper ATPase (CopA) of Thermotoga maritima
J. Biol. Chem.
283
22541-22549
2008
Thermotoga maritima
brenda
Tsuda, T.; Toyoshima, C.
Nucleotide recognition by CopA, a Cu+-transporting P-type ATPase
EMBO J.
28
1782-1791
2009
Archaeoglobus fulgidus (O29777)
brenda
Pilankatta, R.; Lewis, D.; Adams, C.M.; Inesi, G.
High yield heterologous expression of wild-type and mutant Cu+-ATPase (ATP7B, Wilson disease protein) for functional characterization of catalytic activity and serine residues undergoing copper-dependent phosphorylation
J. Biol. Chem.
284
21307-21316
2009
Homo sapiens
brenda
Vllmecke, C.; Drees, S.L.; Reimann, J.; Albers, S.V.; Lbben, M.
The ATPases CopA and CopB both contribute to copper resistance of the thermoacidophilic archaeon Sulfolobus solfataricus
Microbiology
158
1622-1633
2012
Saccharolobus solfataricus, Saccharolobus solfataricus (B2CQV8), Saccharolobus solfataricus PBL2025 (B2CQV8), Saccharolobus solfataricus PBL2025
brenda
Cattoni, D.I.; Gonzalez Flecha, F.L.; Argueello, J.M.
Thermal stability of CopA, a polytopic membrane protein from the hyperthermophile Archaeoglobus fulgidus
Arch. Biochem. Biophys.
471
198-206
2008
Archaeoglobus fulgidus (O29777)
brenda
Rice, W.J.; Kovalishin, A.; Stokes, D.L.
Role of metal-binding domains of the copper pump from Archaeoglobus fulgidus
Biochem. Biophys. Res. Commun.
348
124-131
2006
Archaeoglobus fulgidus (O29777)
brenda
Mandal, A.K.; Argueello, J.M.
Functional roles of metal binding domains of the Archaeoglobus fulgidus Cu(+)-ATPase CopA
Biochemistry
42
11040-11047
2003
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Yang, Y.; Mandal, A.K.; Bredeston, L.M.; Gonzalez-Flecha, F.L.; Argueello, J.M.
Activation of Archaeoglobus fulgidus Cu(+)-ATPase CopA by cysteine
Biochim. Biophys. Acta
1768
495-501
2007
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Mandal, A.K.; Yang, Y.; Kertesz, T.M.; Argueello, J.M.
Identification of the transmembrane metal binding site in Cu+-transporting PIB-type ATPases
J. Biol. Chem.
279
54802-54807
2004
Archaeoglobus fulgidus
brenda
Padilla-Benavides, T.; McCann, C.J.; Argello, J.M.
The mechanism of Cu+ transport ATPases: interaction with CU+ chaperones and the role of transient metal-binding sites
J. Biol. Chem.
288
69-78
2012
Archaeoglobus fulgidus, Archaeoglobus fulgidus (O29777)
brenda
Gonzalez-Guerrero, M.; Argueello, J.M.
Mechanism of Cu+-transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites
Proc. Natl. Acad. Sci. USA
105
5992-5997
2008
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Agarwal, S.; Hong, D.; Desai, N.; Sazinsky, M.; Argello, J.; Rosenzweig, A.
Structure and interactions of the C-terminal metal binding domain of Archaeoglobus fulgidus CopA
Proteins
78
2450-2458
2010
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Villafane, A.A.; Voskoboynik, Y.; Cuebas, M.; Ruhl, I.; Bini, E.
Response to excess copper in the hyperthermophile Sulfolobus solfataricus strain 98/2
Biochem. Biophys. Res. Commun.
385
67-71
2009
Saccharolobus solfataricus (B2CQV8), Saccharolobus solfataricus 98/2 (B2CQV8)
brenda
Tadini-Buoninsegni, F.; Bartolommei, G.; Moncelli, M.R.; Pilankatta, R.; Lewis, D.; Inesi, G.
ATP dependent charge movement in ATP7B Cu+-ATPase is demonstrated by pre-steady state electrical measurements
FEBS Lett.
584
4619-4622
2010
Homo sapiens
brenda
Maezato, Y.; Johnson, T.; McCarthy, S.; Dana, K.; Blum, P.
Metal resistance and lithoautotrophy in the extreme thermoacidophile Metallosphaera sedula
J. Bacteriol.
194
6856-6863
2012
Metallosphaera sedula
brenda
Gonzalez-Guerrero, M.; Hong, D.; Argueello, J.M.
Chaperone-mediated Cu+ delivery to Cu+ transport ATPases: requirement of nucleotide binding
J. Biol. Chem.
284
20804-20811
2009
Archaeoglobus fulgidus, Archaeoglobus fulgidus (O29777)
brenda
Lewis, D.; Pilankatta, R.; Inesi, G.; Bartolommei, G.; Moncelli, M.R.; Tadini-Buoninsegni, F.
Distinctive features of catalytic and transport mechanisms in mammalian sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases
J. Biol. Chem.
287
32717-32727
2012
Homo sapiens
brenda
Banci, L.; Bertini, I.; Ciofi-Baffoni, S.; D'Onofrio, M.; Gonnelli, L.; Marhuenda-Egea, F.C.; Ruiz-Duenas, F.J.
Solution structure of the N-terminal domain of a potential copper-translocating P-type ATPase from Bacillus subtilis in the apo and Cu(I) loaded states
J. Mol. Biol.
317
415-429
2002
Bacillus subtilis (O32220), Bacillus subtilis
brenda
Roman, E.A.; Argello, J.M.; Gonzalez Flecha, F.L.
Reversible unfolding of a thermophilic membrane protein in phospholipid/detergent mixed micelles
J. Mol. Biol.
397
550-559
2010
Archaeoglobus fulgidus (O29777)
brenda
Villafane, A.; Voskoboynik, Y.; Ruhl, I.; Sannino, D.; Maezato, Y.; Blum, P.; Bini, E.
CopR of Sulfolobus solfataricus represents a novel class of archaeal-specific copper-responsive activators of transcription
Microbiology
157
2808-2817
2011
Saccharolobus solfataricus (B2CQV8), Saccharolobus solfataricus 98/2 (B2CQV8)
brenda
Gonzalez-Guerrero, M.; Raimunda, D.; Cheng, X.; Argueello, J.M.
Distinct functional roles of homologous Cu+ efflux ATPases in Pseudomonas aeruginosa
Mol. Microbiol.
78
1246-1258
2010
Pseudomonas aeruginosa
brenda
Xie, L.; Collins, J.F.
Copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein expressed in rat intestinal epithelial cells
Am. J. Physiol. Cell Physiol.
304
C257-C262
2013
Homo sapiens (Q04656)
brenda
Kaler, S.G.
Translational research investigations on ATP7A: an important human copper ATPase
Ann. N. Y. Acad. Sci.
1314
64-68
2014
Homo sapiens (Q04656)
brenda
Gourdon, P.; Sitsel, O.; Lykkegaard Karlsen, J.; Birk M?ller, L.; Nissen, P.
Structural models of the human copper P-type ATPases ATP7A and ATP7B
Biol. Chem.
393
205-216
2012
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Zhou, L.; Singleton, C.; Le Brun, N.E.
CopAb, the second N-terminal soluble domain of Bacillus subtilis CopA, dominates the Cu(I)-binding properties of CopAab
Dalton Trans.
41
5939-5948
2012
Bacillus subtilis (O32220), Bacillus subtilis, Bacillus subtilis 168 (O32220)
brenda
Sudhahar, V.; Urao, N.; Oshikawa, J.; McKinney, R.D.; Llanos, R.M.; Mercer, J.F.; Ushio-Fukai, M.; Fukai, T.
Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase
Diabetes
62
3839-3850
2013
Mus musculus (Q64430), Mus musculus C57/BL6J (Q64430)
brenda
Padilla-Benavides, T.; George Thompson, A.M.; McEvoy, M.M.; Argueello, J.M.
Mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones: the interaction of Escherichia coli CopA and CusF
J. Biol. Chem.
289
20492-20501
2014
Escherichia coli
brenda
Huang, Y.; Nokhrin, S.; Hassanzadeh-Ghassabeh, G.; Yu, C.H.; Yang, H.; Barry, A.N.; Tonelli, M.; Markley, J.L.; Muyldermans, S.; Dmitriev, O.Y.; Lutsenko, S.
Interactions between metal-binding domains modulate intracellular targeting of Cu(I)-ATPase ATP7B, as revealed by nanobody binding
J. Biol. Chem.
289
32682-32693
2014
Homo sapiens (P35670)
brenda
Jain, S.; Farias, G.G.; Bonifacino, J.S.
Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
Mol. Biol. Cell
26
218-228
2015
Homo sapiens (P35670)
brenda
Kenthirapalan, S.; Waters, A.P.; Matuschewski, K.; Kooij, T.W.
Copper-transporting ATPase is important for malaria parasite fertility
Mol. Microbiol.
91
315-325
2014
Plasmodium berghei, Toxoplasma gondii, Plasmodium berghei ANKA
brenda
Drees, S.L.; Beyer, D.F.; Lenders-Lomscher, C.; Luebben, M.
Distinct functions of serial metal-binding domains in the Escherichia coli P1B-ATPase CopA
Mol. Microbiol.
97
423-438
2015
Escherichia coli (A0A061K6S9), Escherichia coli
brenda
Nyasae, L.K.; Schell, M.J.; Hubbard, A.L.
Copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
Traffic
15
1344-1365
2014
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Ashino, T.; Kohno, T.; Sudhahar, V.; Ash, D.; Ushio-Fukai, M.; Fukai, T.
Copper transporter ATP7A interacts with IQGAP1, a Rac1 binding scaffold protein role in PDGF-induced VSMC migration and vascular remodeling
Am. J. Physiol. Cell Physiol.
315
C850-C862
2018
Rattus norvegicus (P70705)
brenda
Sudhahar, V.; Okur, M.N.; Bagi, Z.; OBryan, J.P.; Hay, N.; Makino, A.; Patel, V.S.; Phillips, S.A.; Stepp, D.; Ushio-Fukai, M.; Fukai, T.
Akt2 (protein kinase B beta) stabilizes ATP7A, a copper transporter for extracellular superoxide dismutase, in vascular smooth muscle novel mechanism to limit endothelial dysfunction in type 2 diabetes mellitus
Arterioscler. Thromb. Vasc. Biol.
38
529-541
2018
Homo sapiens (Q04656), Mus musculus (Q64430)
brenda
Mondol, T.; Aden, J.; Wittung-Stafshede, P.
Copper binding triggers compaction in N-terminal tail of human copper pump ATP7B
Biochem. Biophys. Res. Commun.
470
663-669
2016
Homo sapiens (P35670)
brenda
Autzen, H.E.; Koldso, H.; Stansfeld, P.J.; Gourdon, P.; Sansom, M.S.P.; Nissen, P.
Interactions of a bacterial Cu(I)-ATPase with a complex lipid environment
Biochemistry
57
4063-4073
2018
Legionella pneumophila subsp. pneumophila (Q5ZWR1), Legionella pneumophila subsp. pneumophila DSM 7513 (Q5ZWR1)
brenda
Bredeston, L.M.; Gonzalez Flecha, F.L.
The promiscuous phosphomonoestearase activity of Archaeoglobus fulgidus CopA, a thermophilic Cu+ transport ATPase
Biochim. Biophys. Acta
1858
1471-1478
2016
Archaeoglobus fulgidus (O29777), Archaeoglobus fulgidus
brenda
Hilario-Souza, E.; Cuillel, M.; Mintz, E.; Charbonnier, P.; Vieyra, A.; Cassio, D.; Lowe, J.
Modulation of hepatic copper-ATPase activity by insulin and glucagon involves protein kinase A (PKA) signaling pathway
Biochim. Biophys. Acta
1862
2086-2097
2016
Homo sapiens (P35670)
brenda
Gronberg, C.; Sitsel, O.; Lindahl, E.; Gourdon, P.; Andersson, M.
Membrane anchoring and ion-entry dynamics in P-type ATPase copper transport
Biophys. J.
111
2417-2429
2016
Legionella pneumophila subsp. pneumophila (Q5ZWR1), Legionella pneumophila subsp. pneumophila DSM 7513 (Q5ZWR1)
brenda
Fang, T.; Tian, Y.; Yuan, S.; Sheng, Y.; Arnesano, F.; Natile, G.; Liu, Y.
Differential reactivity of metal binding domains of copper ATPases towards cisplatin and colocalization of copper and platinum
Chemistry
24
8999-9003
2018
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Comstra, H.; McArthy, J.; Rudin-Rush, S.; Hartwig, C.; Gokhale, A.; Zlatic, S.; Blackburn, J.; Werner, E.; Petris, M.; D'Souza, P.; Panuwet, P.; Barr, D.; Lupashin, V.; Vrailas-Mortimer, A.; Faundez, V.
The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors
eLife
6
e24722
2017
Homo sapiens (Q04656), Drosophila melanogaster
brenda
Pierson, H.; Muchenditsi, A.; Kim, B.E.; Ralle, M.; Zachos, N.; Huster, D.; Lutsenko, S.
The function of ATPase copper transporter ATP7B in intestine
Gastroenterology
154
168-180.e5
2018
Mus musculus (Q64446)
brenda
Ladomersky, E.; Khan, A.; Shanbhag, V.; Cavet, J.; Chan, J.; Weisman, G.; Petris, M.
Host and pathogen copper-transporting P-type ATPases function antagonistically during Salmonella infection
Infect. Immun.
85
e00351-17
2017
Mus musculus (Q64430), Salmonella enterica subsp. enterica serovar Typhimurium (A0A0H3NA56), Salmonella enterica subsp. enterica serovar Typhimurium SL1344 (A0A0H3NA56)
brenda
Wijekoon, C.J.; Udagedara, S.R.; Knorr, R.L.; Dimova, R.; Wedd, A.G.; Xiao, Z.
Copper ATPase CopA from Escherichia coli quantitative correlation between ATPase activity and vectorial copper transport
J. Am. Chem. Soc.
139
4266-4269
2017
Escherichia coli
brenda
Jayakanthan, S.; Braiterman, L.T.; Hasan, N.M.; Unger, V.M.; Lutsenko, S.
Human copper transporter ATP7B (Wilson disease protein) forms stable dimers in vitro and in cells
J. Biol. Chem.
292
18760-18774
2017
Homo sapiens (P35670)
brenda
Yi, L.; Kaler, S.G.
Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration
J. Biol. Chem.
293
7606-7617
2018
Homo sapiens
brenda
Li, Z.H.; Zheng, R.; Chen, J.T.; Jia, J.; Qiu, M.
The role of copper transporter ATP7A in platinum-resistance of esophageal squamous cell cancer (ESCC)
J. Cancer
7
2085-2092
2016
Homo sapiens
brenda
Zhu, S.; Shanbhag, V.; Wang, Y.; Lee, J.; Petris, M.
A role for the ATP7A copper transporter in tumorigenesis and cisplatin resistance
J. Cancer
8
1952-1958
2017
Mus musculus (Q64430)
brenda
Bossak, K.; Drew, S.C.; Stefaniak, E.; Plonka, D.; Bonna, A.; Bal, W.
The Cu(II) affinity of the N-terminus of human copper transporter CTR1 Comparison of human and mouse sequences
J. Inorg. Biochem.
182
230-237
2018
Homo sapiens (O15431)
brenda
Acevedo, K.; Hayne, D.; McInnes, L.; Noor, A.; Duncan, C.; Moujalled, D.; Volitakis, I.; Rigopoulos, A.; Barnham, K.; Villemagne, V.; White, A.; Donnelly, P.
Effect of structural modifications to glyoxal-bis(thiosemicarbazonato)copper(II) complexes on cellular copper uptake, copper-mediated ATP7A trafficking, and P-glycoprotein mediated efflux
J. Med. Chem.
61
711-723
2018
Homo sapiens (Q04656)
brenda
Ha, J.H.; Doguer, C.; Collins, J.F.
Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells
Metallomics
8
963-972
2016
Rattus norvegicus (D1MCF1), Homo sapiens (Q04656)
brenda
Zhu, S.; Shanbhag, V.; Hodgkinson, V.L.; Petris, M.J.
Multiple di-leucines in the ATP7A copper transporter are required for retrograde trafficking to the trans-Golgi network
Metallomics
8
993-1001
2016
Mus musculus (Q64430)
brenda
Ponnandai Shanmugavel, K.; Petranovic, D.; Wittung-Stafshede, P.
Probing functional roles of Wilson disease protein (ATP7B) copper-binding domains in yeast
Metallomics
9
981-988
2017
Homo sapiens (P35670)
brenda
Meydan, S.; Klepacki, D.; Karthikeyan, S.; Margus, T.; Thomas, P.; Jones, J.E.; Khan, Y.; Briggs, J.; Dinman, J.D.; Vazquez-Laslop, N.; Mankin, A.S.
Programmed ribosomal frameshifting generates a copper transporter and a copper chaperone from the same gene
Mol. Cell
65
207-219
2017
Escherichia coli (Q59385)
brenda
Senovilla, M.; Castro-Rodriguez, R.; Abreu, I.; Escudero, V.; Kryvoruchko, I.; Udvardi, M.K.; Imperial, J.; Gonzalez-Guerrero, M.
Medicago truncatula copper transporter 1 (MtCOPT1) delivers copper for symbiotic nitrogen fixation
New Phytol.
218
696-709
2018
Medicago truncatula
brenda
Petrov, E.; Menon, G.; Rohde, P.; Battle, A.; Martinac, B.; Solioz, M.
Xenon-inhibition of the MscL mechanosensitive channel and the CopB copper ATPase under different conditions suggests direct effects on these proteins
PLoS ONE
13
e0198110
2018
Enterococcus hirae, Enterococcus hirae (P05425), Enterococcus hirae DSM 20160 (P05425)
brenda
Purohit, R.; Ross, M.O.; Batelu, S.; Kusowski, A.; Stemmler, T.L.; Hoffman, B.M.; Rosenzweig, A.C.
Cu+-specific CopB transporter Revising P1B-type ATPase classification
Proc. Natl. Acad. Sci. USA
115
2108-2113
2018
Sphaerobacter thermophilus
brenda
Yu, C.; Lee, W.; Nokhrin, S.; Dmitriev, O.
The Structure of metal binding domain 1 of the copper transporter ATP7B reveals mechanism of a singular Wilson disease mutation
Sci. Rep.
8
581
2018
Homo sapiens (P35670)
brenda
Rupp, J.; Locatelli, M.; Grieser, A.; Ramos, A.; Campbell, P.; Yi, H.; Steel, J.; Burkhead, J.; Bortz, E.
Host cell copper transporters CTR1 and ATP7A are important for influenza A virus replication
Virol. J.
14
1-12
2017
Homo sapiens (Q04656)
brenda
Wang, X.; Guo, L.; Zhang, S.; Chen, Y.; Chen, Y.T.; Zheng, B.; Sun, J.; Qian, Y.; Chen, Y.; Yan, B.; Lu, W.
Copper sulfide facilitates hepatobiliary clearance of gold nanoparticles through the copper-transporting ATPase ATP7B
ACS nano
13
5720-5730
2019
Mus musculus (Q64446)
brenda
Chang, P.K.; Scharfenstein, L.L.; Mack, B.; Wei, Q.; Gilbert, M.; Lebar, M.; Cary, J.W.
Identification of a copper-transporting ATPase involved in biosynthesis of A. flavus conidial pigment
Appl. Microbiol. Biotechnol.
103
4889-4897
2019
Aspergillus flavus (B8NSU6), Aspergillus flavus ATCC 200026 (B8NSU6)
brenda
Placenti, M.A.; Roman, E.A.; Gonzalez Flecha, F.L.; Gonzalez-Lebrero, R.M.
Functional characterization of Legionella pneumophila Cu+ transport ATPase. The activation by Cu+ and ATP
Biochim. Biophys. Acta Biomembr.
1864
183822
2022
Legionella pneumophila subsp. pneumophila (Q5ZWR1), Legionella pneumophila subsp. pneumophila ATCC 33152 (Q5ZWR1)
brenda
Leon-Torres, A.; Arango, E.; Castillo, E.; Soto, C.Y.
CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis
Biol. Res.
53
6
2020
Mycobacterium tuberculosis (P9WPT9), Mycobacterium tuberculosis (A5TYH7), Mycobacterium tuberculosis ATCC 25177 (A5TYH7)
brenda
Lukanovic, D.; Herzog, M.; Kobal, B.; Cerne, K.
The contribution of copper efflux transporters ATP7A and ATP7B to chemoresistance and personalized medicine in ovarian cancer
Biomed. Pharmacother.
129
110401
2020
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Petruzzelli, R.; Polishchuk, R.S.
Activity and trafficking of copper-transporting ATPases in tumor development and defense against platinum-based drugs
Cells
8
1080
2019
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Benes, V.; Leonhardt, T.; Sacky, J.; Kotrba, P.
Two P1B-1-ATPases of Amanita strobiliformis with distinct properties in Cu/Ag transport
Front. Microbiol.
9
747
2018
Amanita strobiliformis (A0A2S1JL61), Amanita strobiliformis (A0A2S1JL48)
brenda
Das, S.; Mohammed, A.; Mandal, T.; Maji, S.; Verma, J.; Ruturaj, J.; Gupta, A.
Polarized trafficking and copper transport activity of ATP7B A mutational approach to establish genotype-phenotype correlation in Wilson disease
Hum. Mutat.
43
1408-1429
2022
Homo sapiens (P35670)
brenda
Escaray, F.; Antonelli, C.; Copello, G.; Puig, S.; Penarrubia, L.; Ruiz, O.; Perea-Garcixada, A.
Characterization of the copper transporters from Lotus spp. and their involvement under flooding conditions
Int. J. Mol. Sci.
20
3136
2019
Lotus japonicus, Lotus japonicus (A0A514TTC0)
brenda
Li, Y.Q.; Yin, J.Y.; Liu, Z.Q.; Li, X.P.
Copper efflux transporters ATP7A and ATP7B Novel biomarkers for platinum drug resistance and targets for therapy
IUBMB Life
70
183-191
2018
Homo sapiens (P35670), Homo sapiens (Q04656)
brenda
Schmidt, K.; Ralle, M.; Schaffer, T.; Jayakanthan, S.; Bari, B.; Muchenditsi, A.; Lutsenko, S.
ATP7A and ATP7B copper transporters have distinct functions in the regulation of neuronal dopamine-beta-hydroxylase
J. Biol. Chem.
293
20085-20098
2018
Mus musculus (Q64430), Mus musculus (Q64446)
brenda
Agnihotry, S.; Dhusia, K.; Srivastav, A.K.; Upadhyay, J.; Verma, V.; Shukla, P.K.; Ramteke, P.W.; Gautam, B.
Biochemical regulation and structural analysis of copper-transporting ATPase in a human hepatoma cell line for Wilson disease
J. Cell. Biochem.
120
18826-18844
2019
Homo sapiens (P35670)
brenda
Shenberger, Y.; Marciano, O.; Gottlieb, H.; Ruthstein, S.
Insights into the N-terminal Cu(II) and Cu(I) binding sites of the human copper transporter CTR1
J. Coord. Chem.
71
1985-2002
2018
Homo sapiens (O15431)
-
brenda
Kwok, M.L.; Chan, K.M.
Functional characterization of copper transporters zCtr1, zAtox1, zAtp7a and zAtp7b in zebrafish liver cell line ZFL
Metallomics
11
1532-1546
2019
Danio rerio
brenda
Bitter, R.M.; Oh, S.; Deng, Z.; Rahman, S.; Hite, R.K.; Yuan, P.
Structure of the Wilson disease copper transporter ATP7B
Sci. Adv.
8
eabl5508
2022
Xenopus tropicalis (A0A6I8QA66)
brenda
Yang, K.; Shadkchan, Y.; Tannous, J.; Landero Figueroa, J.A.; Wiemann, P.; Osherov, N.; Wang, S.; Keller, N.P.
Contribution of ATPase copper transporters in animal but not plant virulence of the crossover pathogen Aspergillus flavus
Virulence
9
1273-1286
2018
Aspergillus flavus (A0A7U2QZR2), Aspergillus flavus (A0A7U2QY81)
brenda
EXTERNAL LINKS (specific for EC-Number 7.2.2.8)
Transporter Classification Database (TCDB): 3.A.3.5.19, 3.A.3.5.11, 3.A.3.5.32, 3.A.3.5.6, 3.A.3.5.3, 3.A.3.5.2, 3.A.3.5.5, 3.A.3.5.1, 3.A.3.5.29, 3.A.3.5.17, 3.A.3.5.7, 3.A.3.5.18, 3.A.3.5.41, 3.A.3.5.15, 3.A.3.5.37
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Release 2026.1 (March 2026)
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