Information on EC 3.6.3.4 - Cu2+-exporting ATPase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY hide
3.6.3.4
-
RECOMMENDED NAME
GeneOntology No.
Cu2+-exporting ATPase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + Cu2+[side 1] = ADP + phosphate + Cu2+[side 2]
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
transmembrane transport
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (Cu2+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. The enzyme from the termophilic bacterium Archaeoglobus fulgidus is involved in copper extrusion from the cell [1,2].
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
strain HITO7711, gene CCC2
-
-
Manually annotated by BRENDA team
strain HITO7711, gene CCC2
-
-
Manually annotated by BRENDA team
gene BcCcc2, BC1G_10836
-
-
Manually annotated by BRENDA team
gene BcCcc2, BC1G_10836
-
-
Manually annotated by BRENDA team
gene ctpA or ccoI
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene ATP7A
-
-
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene pcpA
UniProt
Manually annotated by BRENDA team
gene pcpA
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain 3D7
-
-
Manually annotated by BRENDA team
gene ctpA or ccoI
-
-
Manually annotated by BRENDA team
PCC7942
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + H2O + cisplatin/in
ADP + phosphate + cisplatin/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + Cu+/in
ADP + phosphate + Cu+/out
show the reaction diagram
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
show the reaction diagram
ATP + H2O + Cu2+in
ADP + phosphate + Cu2+out
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cu+/in
ADP + phosphate + Cu+/out
show the reaction diagram
-
-
-
-
?
ATP + H2O + Cu2+/in
ADP + phosphate + Cu2+/out
show the reaction diagram
ATP + H2O + Cu2+in
ADP + phosphate + Cu2+out
show the reaction diagram
-
CopB drives the efflux of Cu2+ from the cell
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
activity slightly above background as measured in the absence of any such ion; activity slightly above background as measured in the absence of any such ion
copper
-
the enzyme contains two Cu(I)-binding sites. Copper binding within the His-Met-loop stabilizes Cu(I) and protects it from oxidation, which may further aid the transfer of copper from ATP7A to acceptor proteins
Iron
-
used instead of copper also stimulates ATPase and phosphorylation
KCl
-
ATPase activity increases with increasing salt concentration
NaCl
-
ATPase activity increases with increasing salt concentration
NaSCN
-
activates
Ni2+
activity slightly above background as measured in the absence of any such ion; activity slightly above background as measured in the absence of any such ion
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Bathocuproine disulfonate
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a copper chelator, reduced ATP7B activity
cisplatin
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DDP, shown to inhibit the transport of copper, pH 4.6
Cu2+
-
shown to inhibit the transport of cisplatin
ebselen
-
-
NaBr
-
240 mM, reduces activity
NaNO3
-
240 mM, reduces activity
PCMB
-
-
thiol
activity of CtrA3 decreased at concentrations of 20 mM and above
vanadate
additional information
-
in hepatocytes, ATP7B-mediated efflux does not play a major role in determining cell sensitivity to cis-diamminedichloroplatinum
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Atx1
-
the metallo-chaperone Atx1 interacts with the N-terminus of Ccc2 essentially required for the copper delivery to the trans-Golgi network. Atx1 does not activate the Ccc2-derived ATPase lacking its N-terminus
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cis-diamminedichloroplatinum
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DDP, stimulates catalytic phosphorylation of ATP7B
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cysteine
stimulated by, optimum concentration of 15 mM for CtrA3; stimulated by, optimum concentration of 20 mM
dithioerythritol
-
GSH, dithiothreitol or dithioerythritol are required for activity
dithiothreitol
-
GSH, dithiothreitol or dithioerythritol are required for activity
glutaredoxin
-
is essential for ATPase function and catalysis either the reduction of intramolecular disulphide bonds or the deglutathionylation of the cysteine residues within the CxxC motifs to facilitate copper-binding for subsequent transport; is essential for ATPase function and catalysis either the reduction of intramolecular disulphide bonds or the deglutathionylation of the cysteine residues within the CxxC motifs to facilitate copper-binding for subsequent transport
glutaredoxin-1
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is essential in interaction with ATP7A and ATP7B via their N-termini for stabilizing their activities
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GSH
-
GSH, dithiothreitol or dithioerythritol are required for activity
Insulin
-
increase of mRNA and protein levels of ATP7A
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NaCl
activity stimulated by, plateau at 400 mM; CtrA2 and CtrA3, stimulated by, plateau at 400 mM
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0009 - 2.02
ATP
additional information
additional information
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Km-value for copper varies insignificantly between different mutants and wild-type enzyme
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.081
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partially purifed recombinant ATP7B in microsomes, copper-dependent, steady-state ATPase, 37°C, pH 6.0, in presence of copper and copper chelator
0.112
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partially purifed recombinant ATP7B in microsomes, copper-dependent, steady-state ATPase, 37°C, pH 6.0 in presence of copper
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
assay at
6.9
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transport assay at
7
activity of CtrA3 stimulated by Cu2+; CtrA2 protein stimulated by Ag+
7.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.6 - 6.9
-
ability of wild-type ATP7B to transport copper when exposed to 2 microM copper shown to be greater at pH 4.6 than at pH 6.9, ATP-dependent accumulation of cisplatin shown at 4.6
5 - 9
ATPase activities stimulated by Ag+; ATPase activities stimulated by Cu2+ measured at different pH values
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
75
thermophilic protein, activity maximum at; thermophilic protein, activity maximum at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 90
maximum at 75°C, decreased to between 50% and 70% of this value at 90°C, significantly active down to 50°C; maximum at 75°C, shown to be decreased to between 50% and 70% of this value at 90°C, shown to be completely inactive at 50°C or below
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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cellular distribution of ATP7B, stable ATP7B pool localized to the tight junctions that seal the bile canaliculi shown
Manually annotated by BRENDA team
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ATP7B is expressed in bile duct epithelial cells, where it may mediate copper secretion into bile fluid
Manually annotated by BRENDA team
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expression is greater in lactating tissue than in nonlactating tissue, detected in luminal epithelial cells of the alveoli and ducts but not in myoepithelial cells
Manually annotated by BRENDA team
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copper-resistant CHO cells which overexpress the enzyme
Manually annotated by BRENDA team
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ATP7A shown to be expressed in 23.5% of clinical colon cancer specimens but not in the adjacent normal epithelium
Manually annotated by BRENDA team
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Menkes disease protein, i.e. ATP7A
Manually annotated by BRENDA team
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ATP7A is present on apical domains of duodenal enterocytes in control rats and on brush-border and basolateral membrane domains in iron-deprived rats
Manually annotated by BRENDA team
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airway, cell type-specific expression of ATP7A and ATP7B in airway epithelial cells
Manually annotated by BRENDA team
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ATP7A and ATP7B
Manually annotated by BRENDA team
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the overexpression of ATP7B in hepatocellular carcinoma might be associated with unfavorable clinical outcome in patients treated with cisplantin-based chemotherapy
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
ATP7A expressed in
Manually annotated by BRENDA team
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larval stage, copper-inducible
Manually annotated by BRENDA team
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ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum
Manually annotated by BRENDA team
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heterologous expression into Xenopus laevis
Manually annotated by BRENDA team
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presence of ATP7A in the axons of postnatal, but not adult, optic nerve
Manually annotated by BRENDA team
Menkes protein could be involved in copper secretion from acinar cells into saliva
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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inner membrane of the chloroplast envelope
Manually annotated by BRENDA team
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within ARPE-19 cell the Wilson disease protein shows a perinuclear and cytoplasmic distribution
Manually annotated by BRENDA team
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COMM-domain-containing 1 maintains the amount of Atp7b and facilitates recruitment of the enzyme from cytoplasmic vesicles to the trans-Golgi network membrane
Manually annotated by BRENDA team
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mainly localized in the late endosomes in both the steady and copper-loaded states. ATP7B translocates copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes
Manually annotated by BRENDA team
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in HepG2 cells, elevated copper levels stimulates trafficking of ATP7B to pericanalicular vesicles. Mutations of an endocytic retrieval signal in ATP7B cause the protein to constitutively localize to vesicles and not to plasma membrane. The vesicular compartment is the final trafficking destination for ATP7B
Manually annotated by BRENDA team
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within ARPE-19 cell the Wilson disease protein shows a perinuclear and cytoplasmic distribution
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Manually annotated by BRENDA team
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ATP7B interaction with p62 is a key component of the copper-induced trafficking pathway that delivers ATP7B to subapical vesicles of hepatocytes for the removal of excess copper into bile
-
Manually annotated by BRENDA team
heterogeneous distribution, small clusters
Manually annotated by BRENDA team
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the enzyme redistributes from Golgi apparatus into vesicles in high copper conditions
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
ORGANISM
UNIPROT
Archaeoglobus fulgidus (strain ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126)
Archaeoglobus fulgidus (strain ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126)
Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
75000
CtrA3 protein, SDS-PAGE
110000
x * 110000, SDS-PAGE
150000
-
x * 150000, SDS-PAGE
165000
180000
-
x * 180000, ATP7A, SDS-PAGE, x * 165000, ATP7B, SDS-PAGE
195000
-
x * 195000, GST-tagged enzyme, SDS-PAGE
298600
-
calculated from amino acid sequence
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
additional information
-
ATP7B in Hep-G2 and HEK-293 cells differ in size, but not in post-translational modifications
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
electron cryomicroscopy of two-dimensional crystals, projection map at 7 A resolution with density peaks
crystallization and structure determination of the the apo- and phosphate-bound ATP-binding domain, hanging drop vapour diffusion method
-
solution structures of ATP-free and ATP-bound N-MNK
crystallization trials are performed at 18 °C by vapor diffusion using the hanging-drop technique, crystal structure of the catalytic fragment of a Sulfolobus solfataricus P-type ATPase, CopB-B, is determined with a 2.6 A resolution.In CopB-B crystals, a bound sulfate anion is identified at the phosphate-binding location. In solution state bound phosphate can be readily displaced by orthovanadate at submillimolar concentration as well as by sulfate at millimolar concentration. It is possible to assign the structure of the sulfate-bound phosphorylation domain of CopB-B to a state related to an enzyme/phosphate intermediate state of the catalytic cycle
hangimg drop vapour diffusion method, 3D crystals of CopB-B, the 29 kDa catalytic ATP binding/phosphorylation domain are produced, which diffracted to a resolution of 2.2 A
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the C-terminus of ATP7B is necessary for protein stability
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
chitin resin column chromatography
-
enzyme is truncated by 5 of the six metal binding domains and endowed with an N-terminal histidine-tag for affinity purification, recombinantly expressed in Escherichia coli and reconstituted into proteoliposomes
-
fusion protein of glutathione-S-transferase and Wilson-disease protein expressed in Escherichia coli
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gel filtration; gel filtration
isolation of membrane vesicles from yeast expressing recombinant enzyme
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purification of fusion protein by chitin affinity chromatography
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purification of three different soluble domains of the protein (CopB-A), CopB-B (ATP binding/phosphorylation domain), and CopB-C (cation binding domain)
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recombinant ATP-binding domain
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recombinant ATP7B from Spodoptera frugiperda Sf9 cell membranes
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recombinant His-tagged ATP7A or MNK from Escherichia coli strain BL21(DE3)
recombinant myc-tagged ATP7B is isolated from the microsomal fraction of COS-1 cell homogenates
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recombinantly expressed domain 1, 3, 4, 5 and 6
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP7A and ATP7B genotyping
-
ATP7A is located on Xq13.2-13.3, spans about 150 kb and has 23 exons, ATP7B is located on chromosome 13, spans about 80 kb and contains 21 exons, ATP7A and ATP7B expression pattern analysis, overview
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ATP7B expression in Sf9 insect cells, epitope-tagged ATP7B-HA56 variant generated and expressed in oocytes of Xenopus laevis, N-terminal and C-terminal deletions included to analyze delivery of ATP7B-HA56 from the membrane, wild-type ATP7B used as a control
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CHO-K1 cells are transfected with wild-type human MNK cDNA
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cloning of the 5'-end of the Wilson disease gene ATP7B
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cloning of the DNA segment coding for the N-terminal copper-binding region into a GST pGEX-6P-2 vector
co-expression of Atx1 and Ccc2 mutants in an atx1Dccc2D yeast strain
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construction and expression of the fusion protein of glutathione-S-transferase and Wilson-disease protein and expression in Escherichia coli
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DNA sequence and genetic structure analysis of ATP7B from renal and hepatic tissue and comparison, recombinant ATP7B expressed in renal cells is similar to hepatic protein in size and trafficking, ATP7B lacking the exon 1 sequence shows cell-specific trafficking in polarized renal and hepatic cells, overview
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Drosophila transformation vector pW8 used, generation of transgenic lines and construction of a EYFP-DmATP7 fusion protein for localization studies described
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enzyme is expressed using pGEX-4T-2, subcloned into pGEX-6P-2 and expressed in Escherichia coli strain BL21
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expressed in Escherichia coli
expressed in HEK-293T cells; expressed in HEK-293T cells
expressed in Hepa 1-6 cells
-
expressed in Lactococcus lactis
-
expressed in Madin-Darby canine kidney cells
-
expressed in Saccharomyces cerevisiae copper-transporting ATPase Ccc2-deficient cells
-
expressed in Sf9 insect cells
expressed in SV40-transformed Menkes-null fibroblasts
-
expression in CHO-K1 cells
-
expression in Escherichia coli
-
expression in Escherichia coli as a GST fusion protein
-
expression in Escherichia coli of the metal binding domain
-
expression in Escherichia coli of the N-domain fused with a chitin-binding domain, several N-domain mutants cloned using the same procedure
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expression in Escherichia coli; expression in Escherichia coli
expression in Saccharomyces cerevisiae
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expression in Spodoptera frugiperda Sf-9 cells; infection of Sf9 cells with baculoviral constructs encoding wild-type ATP7B and a mutant variant unable to transport copper
-
expression of a chimeric metal bidnding sequence with the Menkes disease protein carrying the binding motif of bacterial Hg(II) binding protein MerP. This chimeric protein shows differences in structure and the dynamics of the binding site that may account for metal specificity
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expression of ATP7B in Spodoptera frugiperda Sf9 cell membranes via baculovirus transfection, overexpression of ATP7B in ovary cells causes increased cellular resistance to cisplatin, a chemotherapeutic agent
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expression of domain 1, 3, 4, 5 and 6 in Escherichia coli
expression of Menkes disease protein with an N-terminal Glu-Glu tag in Sf9 cells
-
expression of mutant enzymes in MDCK cells and in CHO cells
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expression of the ATP-binding domain in Escherichia coli
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expression of the DNA sequence encoding MNK3, corresponding to amino acids 275-352 of ATP7A in Escherichia coli strain BL21 (DE3)pLysS. Introduction of a C-terminal expression tag including His6 to ease purification
-
expression of the wild type and mutant proteins in Saccharomyces cerevisiae
-
expression of the wild type and truncated mutants in COS-7 cells
-
expression of three different soluble domains of the protein (CopB-A (phosphatase domain), CopB-B, and CopB-C) in Escherichia coli
-
expression of wild type and several mutants in Saccharomyces cerevisiae and CHO cells
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expression of wild-type and mutant ATP7B ATP binding loops in ccc2-deficient Saccharomyces cerevisiae strain
expression of wild-type and mutant myc-tagged ATP7Bs in COS1 cells using an adenoviral vector
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gene ATP7A, genetic mapping and expression analysis of splicing variants, overview
gene ATP7A, located on chromosome Xq13.1-q21, genotyping
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gene ATP7A, overexpression of His-tagged ATP7A or MNK in Escherichia coli strain BL21(DE3), overexpression of the soluble nucleotide-binding domain of MNK protein, comprising amino acids 1051-1231
gene ATP7B, expression in HEK-293 cells and in mesenchymal stem cells derived from bone marrow, viability of these cells is significantly enhanced after ATP7B transduction, expression analysis, overview
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gene BcCcc2, DNA and amino acid sequence determination and analysis, phylogenetic analysis
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gene CCC', DNA and amino acid sequence determination and analysis, phylogenetic analysis
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gene pcpA, cDNA and amino acid sequence determination and analysis, quantitative real-time PCR expression analysis and sequence comparison, overview
genetic architecture of Cu tolerance, overview
mutant variants of ATP7B expressed in protease-deficient Saccharomyces cerevisiae strain BJ2168 and in ccc2 and fet3 mutant strains lacking functional CCC2 and FET3 genes
-
overexpression of ATP7A and ATP7B in Me32a cells mediating resistance to bioavailable platinum analogue agents DDP and JM118, expression of ATP7A and ATP7B in the two-hydrid expression system for interaction analysis
-
rescue and correction of the Cu accumulation defect by expression of wild type MNK in non-polarized BHK cells
-
the catalytic fragment CopB-B is expressed in Escherichia coli
the enzyme is truncated by 5 of the six metal binding domains and endowed with an N-terminal histidine-tag for affinity purification. This construct is able to functionally complement a yeast strain defective in its native copper ATPase CCC2. Expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
COMM-domain-containing 1 knockdown reduces the expression of Atp7b, and abolishes the relocation of Atp7b back from the periphery to the trans-Golgi network membrane
-
iron deprivation induces all three splicing variants 5-7fold
isoform PAA2 protein abundance decreases significantly and specifically when Cu in the media is increased. Copper addition does not affect PAA2 transcript levels, but stability of the PAA2 protein is decreased in plants grown with elevated copper levels
-
PAA2 protein abundance is significantly increased in paa1 mutants, in which the copper content in the chloroplast is half of that of the wild-type, due to impaired copper import into the organelle. In a pc2 insertion mutant, which has strongly reduced plastocyanin expression, the PAA2 protein levels are low regardless of copper addition to the growth media
-
synthesized at low levels under standard growth conditions (i.e. under copper limitation), and the expression levels increases after addition of copper
-
-
synthesized at low levels under standard growth conditions (i.e. under copper limitation), and the expression levels increases after addition of copper; synthesized at low levels under standard growth conditions (i.e. under copper limitation), and the expression levels increases after addition of copper
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D598A
-
inactive
N923T
mutation in the Cvi allele in the tightly conserved domain N(x)6YN(x)4P, is a cause of dysfunction of the Cvi HMA5 allele
delM1-M54
-
a truncated CopB lacking the first 54 amino acids is constructed to characterize the N-terminal metal binding domain. This enzyme shows reduced ATPase activity (50% of wild type) but no changes in metal selectivity, ATP dependence, or phosphorylation levels
C1375S
-
the mutant exhibits trafficking behavior similar to that observed for the wild type enzyme
C983A/C985A
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site-directed mutagenesis of CXC copper binding motif in the transmembrane copper site TM6, absence of alkali labile phosphoenzyme formation
D1027A
-
inactivating mutation of catalytic Asp1027, surface targeting
D1027N
-
site-directed mutagenesis of the P domain, absence of alkali labile phosphoenzyme formation
D1230A
-
retains 21% of the activity compared to wild type
D1267V
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
D40A
-
site-directed mutagenesis, inactive mutant
DD1219/1220AA
-
retains 80% of the activity compared to wild type
E1064A
-
the mutation abolishes ATP binding to the N-domain. In the cell, neither the stability nor targeting of mutant E1064A to the trans-Golgi network differs significantly from the wild type enzyme
E1064K
-
located in the ATP-binding domain, marked impairment in copper transport function, identified as disease-causing mutation
E1173G
naturally occuring mutation in the ATP-binding loop of ATP7B, temperature-sensitive mutant, unable to complement the enzyme-deficient yeast mutant at 37°C, but complement the enzyme-deficient yeast mutant at 30°C
E45A
-
site-directed mutagenesis, inactive mutant
F37A
-
site-directed mutagenesis, the mutant is partially copper-responsive
F39A
-
site-directed mutagenesis, inactive mutant
F39W
-
site-directed mutagenesis, inactive mutant
G1000R
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
G1101R
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
G1176E
naturally occuring mutation in the ATP-binding loop of ATP7B, intermediate mutant, unable to grow at 37°C without addition of copper or iron
G1287S
naturally occuring mutation in the ATP-binding loop of ATP7B, intermediate mutant, unable to grow under iron limitation
G43A
-
site-directed mutagenesis, inactive mutant
G853R
the mutation occurring in the A-domain of ATP7A affects the network of communication with the other domains of the enzyme
G860V
the mutation occurring in the A-domain of ATP7A destabilizes the fold of the domain
H1069Q
-
thermolabile mutant with impaired ATP binding. The mutation greatly destabilizes protein both in vitro and in cells
H1086Q
-
retains 20% of the activity compared to wild type
I1102T
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
I1148T
naturally occuring mutation in the ATP-binding loop of ATP7B, mild mutation, unable to grow under iron limitation
K1097A
-
retains 91% of the activity compared to wild type
K1233M
-
retains 17% of the activity compared to wild type
L1043P
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
L1083F
-
partial complementation at 30°C, severe deficit at 37°C observed, marked impairment in copper transport function found, identified as disease-causing mutation
L1373P
-
the mutant exhibits abnormal trafficking behavior, the half-life of the mutant protein is significantly shorter than that of the wild type enzyme
L1373R
-
the mutant exhibits abnormal trafficking behavior, the half-life of the mutant protein is significantly shorter than that of the wild type enzyme
L873R
the mutation occurring in the A-domain of ATP7A affects the network of communication within the domain
M1169V
-
partial complementation at 30°C and 37°C observed, partial reduction in ATP7B function´´, identified as disease-causing mutation
M672G/M674A/H676A/H677G/H682A/H683G
-
the mutant shows decreased affinity for copper. The mutations within the His/Met-rich segment Met672-Pro707 (HM-loop) do not prevent the ability of the enzyme to form a phosphorylated intermediate during ATP hydrolysis but inhibit subsequent dephosphorylation, a step associated with copper release
M687A/M692A
-
the mutant shows decreased affinity for copper. The mutations within the His/Met-rich segment Met672-Pro707 (HM-loop) do not prevent the ability of the enzyme to form a phosphorylated intermediate during ATP hydrolysis but inhibit subsequent dephosphorylation, a step associated with copper release
N1366A
-
inactive
N41A
-
site-directed mutagenesis, the mutant is partially copper-responsive
N41S
-
site-directed mutagenesis, the mutant is partially copper-responsive
P1379
-
the mutant exhibits trafficking behavior similar to that observed for the wild type enzyme
P1386S
-
naturally occuring mutation, a transition mutation of c.4156C>T in exon 22
R1208G
-
retains the activity of the wild type
R1228T
naturally occuring mutation in the ATP-binding loop of ATP7B, the mutant behaves similar to the wild-type enzyme, complements the enzyme-deficient yeast mutant
S1432A
-
site-directed mutagenesis of a constitutively phosphorylated site, mutation leads to mislocation of the enzyme in presence of Cu2+
S1469A
-
site-directed mutagenesis of a copper-responsive phosphorylation site, mutation leads to mislocation of the enzyme in presence of Cu2+
T1434M
-
the mutant exhibits trafficking behavior similar to that observed for the wild type enzyme
T991M
naturally occuring mutation in the ATP-binding loop of ATP7B, mild mutation
T994I
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naturally occuring mutation, a transition mutation of c.2981C>T in exon 15
V1106D
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located in the ATP-binding domain, marked impairment in copper transport function, identified as disease-causing mutation
V1239G
naturally occuring mutation in the ATP-binding loop of ATP7B, deleterious mutation, unable to grow under iron limitation
V42A
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site-directed mutagenesis, inactive mutant