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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]
ATP + H2O + Cu+
ADP + phosphate + Cu+
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-
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
additional information
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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 + Ag+[side 1]
ADP + phosphate + Ag+[side 2]
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]
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]
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]
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-
-
-
?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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]
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]
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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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]
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]
mechanism of Cu+ transfer
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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]
-
-
-
?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
-
-
?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
-
-
-
?
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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CopA forms a phosphorylated intermediate
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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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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-
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?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
ATP hydrolysis supplies energy for copper transport
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ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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]
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-
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?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
-
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-
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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]
-
-
-
?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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-
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?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
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additional information
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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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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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in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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additional information
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in absence of other ligands, CopZ transfers Cu+ to the wild type enzyme CopA
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additional information
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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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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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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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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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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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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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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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the enzyme also shows Ag+-dependent ATPase activity
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additional information
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the enzyme also shows Ag+-dependent ATPase activity
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evolution
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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
the enzyme belongs to the P-type ATPases
evolution
the enzyme belongs to the PIB-ATPase family, phylogenetic analysis and tree
evolution
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an evolutionarily highly conserved, copper-transporting P-type ATPase in the murine malaria model parasite Plasmodium berghei
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evolution
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the enzyme belongs to the PIB-ATPase family, phylogenetic analysis and tree
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malfunction
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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
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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
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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
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
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
Menkes disease results from loss-of-function mutations in ATP7A
malfunction
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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
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
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
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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
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malfunction
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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
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physiological function
couple the energy of ATP hydrolysis to heavy metal ion translocation across membranes
physiological function
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ATP7B is a copper dependent P-type ATPase, required for copper homeostasis
physiological function
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Escherichia coli CopA is a copper ion-translocating P-type ATPase that confers copper resistance
physiological function
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isoform CtrA2 presumably transports reduced Cu+, while isoform CtrA3 presumably transports the oxidized Cu+
physiological function
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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
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 enzyme couples the hydrolysis of ATP to the efflux of cytoplasmic Cu+
physiological function
the enzyme is involved in transporting Cu+ throughout biological membranes
physiological function
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the enzyme is required for copper homeostasis
physiological function
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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
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
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
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
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
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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
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
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
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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
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
ATP7A interacts with hundreds of proteins present in different compartments within cells
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
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
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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
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
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
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
enzyme specifically transports Cu(I) , but Ctr1 peptides bind Cu(II) at an amino terminal high-affinity Cu(II), Ni(II) (ATCUN) site. Ascorbate-dependent reduction of the Cu(II)-high-affinity Cu(II), Ni(II) (ATCUN) site is possible by virtue of an adjacent bis-His motif. Changes in the sequence proximity of the high-affinity site and bis-His motif lead to significant differences in coordination structure and chemical behavior
physiological function
Fe uptake and efflux are impaired by Atp7a silencing
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
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
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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
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
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
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
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
-
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
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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
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physiological function
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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
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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
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physiological function
-
the enzyme ATP7A plays a critical role in delivering cofactor copper to extracellular superoxide dismutase SOD3 for its full activation
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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
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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
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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
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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
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
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
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
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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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
C382A
the mutant exhibits reduced copper binding activity
C751A/C754A
the mutant enzyme has no significant effect on ATPase activity, enzyme phosphorylation, apparent binding affinities of ligands, or E1-E2 equilibrium
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
M711C
-
no Cu+/ATPase activity
N683A
-
no Cu+/ATPase activity
N683Q
-
no Cu+/ATPase activity
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
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
S715R
-
no Cu+/ATPase activity
Y682S
-
Cu+/ATPase activity is about 10% of the activity of the wild-type enzyme
C14A/C17A/C110A/C113A
-
increase in affinity for Cu(II)
C14S/C17S
site-directed mutagenesis, a dysfunctional non-copper-binding mutant
C479A
-
mutation results in lost of resistance to copper
C481A
-
mutation results in lost of resistance to copper
C481H
-
mutation results in lost of resistance to copper
D207A/N208A/M209A/M210A
-
site-directed mutagenesis
E287A
-
site-directed mutagenesis
E287C
-
site-directed mutagenesis
K23A/K30A/K31A/H35A/R50A
-
site-directed mutagenesis
M204A
-
site-directed mutagenesis
M204C
-
site-directed mutagenesis
M279A/E280A/H283A
-
site-directed mutagenesis
T212A/D214A/N215A/S217A
-
site-directed mutagenesis
W273A/W276A/F277A
-
site-directed mutagenesis
W797A/T800A/T802A
-
site-directed mutagenesis
C575A/C578A
-
mutation in the 6th copper site of the NMBD, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
D1027N
-
the mutant is less phosphorylated than the wild type enzyme
G85V
mutation involved in Wilson disease. Mutation causes disruption of the structure of metal-binding domain MBD1
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
significant reduction of activity
K135S/K142S
almost complete loss of activity
K142S
significant reduction of activity
R136S
significant reduction of activity
K135E/R136E
-
almost complete loss of activity
-
K135S
-
significant reduction of activity
-
K142S
-
significant reduction of activity
-
R136S
-
significant reduction of activity
-
H479Q
-
the mutant is unable to utilize ATP, whereas phosphorylation by phosphate is retained
D336A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
D336A
the mutant shows increased Vmax value compared to the wild type enzyme
D336C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
D336C
the mutant shows increased Vmax value compared to the wild type enzyme
E205A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
E205A
the mutant shows increased Vmax value compared to the wild type enzyme
E205C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
E205C
the mutant shows increased Vmax value compared to the wild type enzyme
M158A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
M158A
the mutant shows reduced Vmax value compared to the wild type enzyme
M158C
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
M158C
the mutant shows increased Vmax value compared to the wild type enzyme
M711A
-
no Cu+/ATPase activity
M711A
the mutant exhibits reduced copper binding activity
S139A/G140A
free Cu+/ATPase activity kinetic parameters and binding stoichiometry of wild type and mutant 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
S139A/G140A
the mutant shows increased Vmax value compared to the wild type enzyme
S715A
-
no Cu+/ATPase activity
S715A
the mutant exhibits reduced copper binding activity
Y682A
-
no Cu+/ATPase activity
Y682A
the mutant exhibits reduced copper binding activity
C983A/C985A
-
mutation in the transmembrane copper binding site, TMBS, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
C983A/C985A
-
the mutant is less phosphorylated than the 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
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
-
interaction analysis of recombinant wild-type and mutant enzymes CopA and chaperones CusF, 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
-
disruption of gene copB 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
-
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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
J. Mol. Biol.
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, Saccharolobus solfataricus PBL2025 (B2CQV8)
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
Drosophila melanogaster, Homo sapiens (Q04656)
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
Salmonella enterica subsp. enterica serovar Typhimurium (A0A0H3NA56), Mus musculus (Q64430), 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
Schwab, S.; Shearer, J.; Conklin, S.E.; Alies, B.; Haas, K.L.
Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2
J. Inorg. Biochem.
158
70-76
2016
Homo sapiens (O15431)
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 (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