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Information on EC 7.2.2.8 - P-type Cu+ transporter and Organism(s) Homo sapiens and UniProt Accession Q04656
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7.2.2.8 P-type Cu+ transporterIUBMB Comments
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme transports Cu+ or Ag+, and cannot transport the divalent ions, contrary to EC 7.2.2.9, P-type Cu2+ transporter, which mainly transports the divalent copper ion.
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
slc31a1, copt1, ctra2, cu(+)-atpase, copa1, copa2, copper-transporting atpase 2, ctra3, cu atpase, copper export atpase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP7B
Cu+-exporting ATPase
-
-
-
-
Wilson disease protein
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (P-type, Cu+-exporting)
A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme transports Cu+ or Ag+, and cannot transport the divalent ions, contrary to EC 7.2.2.9, P-type Cu2+ transporter, which mainly transports the divalent copper ion.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
ATP hydrolysis supplies energy for copper transport
-
-
?
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
metal ion binding to the N-terminal copper-sensing domain of ATP7B
-
-
?
additional information
?
-
-
ATP7A/B ATPase utilizes ATP through formation of a phosphoenzyme intermediate whereby phosphorylation potential affects affinity and orientation of bound cation
-
-
?
additional information
?
-
-
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + Cu+[side 1]
ADP + phosphate + Cu+[side 2]
ATP hydrolysis supplies energy for copper transport
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cu2+
copper
Cu2+
copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
Cu2+
copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
Cu2+
copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein expressed in rat intestinal epithelial cells. Copper has a direct influence on Atp7a protein expression independent of changes in mRNA levels
copper
the four most N-terminal metal-binding domains in ATP7B, upon stoichiometric copper addition, adopt a more compact arrangement with higher thermal stability than in the absence of copper. No stable complex was found in solution between the metal-binding domains and the nucleotide-binding domain of ATP7B
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cisplatin
comparison of different metal-binding domains of ATPases based on their reactivity towards cisplatin. The rate of platination is generally greater for holo-metal-binding domains than for apo-metal-binding domains. The platinum binding weakens the CuI coordination, but does not expel the copper ion from metal-binding domains
glyoxal-bis(N-4,4-pyrolidine-3-thiosemicarbazonato)copper(II)
treatment of SKOV-3 cells with micromolar concentrations leads to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane
-
glyoxal-bis(N-4-methyl-3-thiosemicarbazonato)copper(II)
treatment of SKOV-3 cells with micromolar concentrations leads to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane
-
cisplatin
comparison of different metal-binding domains of ATPases based on their reactivity towards cisplatin. The rate of platination is generally greater for holo-metal-binding domains than for apo-metal-binding domains. The platinum binding weakens the CuI coordination, but does not expel the copper ion from metal-binding domains
glucagon
physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. The opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases PKA and PKB/Akt
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
additional information
the enzyme's heavy-metal binding domains may interact with the core of the proteins to achieve autoinhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Insulin
insulin reverses the effect of copper and stimulates retrograde trafficking of ATP7B from the canalicular membranes, consistent with the enhanced ability of ATP7B to sequester copper away from the cytosol. Physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. The opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases PKA and PKB/Akt
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
select areas of the brain, including the developing central nervous system
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
enzyme ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon. Addition of high Cu2+ concentrations cause loss of somatodendritic polarity of ATP7B. High Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
Cu levels regulate the reversible trafficking of endogenous ATP7B in polarized WIF-B cells
additional information
Cu2+ directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
additional information
Cu-directed trafficking of both endogenous and exogenous ATP7B
additional information
Cu-directed trafficking of both endogenous and exogenous ATP7B
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme localization at high copper concentration
enzyme localization at low copper concentration
luminal acidification is required for the cell to redirect ATP7B to the apical domain and maintain it there under conditions of high Cu. Deacidification prevents Cu-directed delivery to apical domain
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
additional information
copper regulates the intracellular localization of copper transporter ATP7B, transient interactions between the N-terminal metal-binding domains and modulated intracellular localization of ATP7B, molecular mechanism
-
Cu2+ directs ATP7B to the apical domain of hepatic cells via basolateral endosomes
high Cu2+ concentration redistributes ATP7B to late endosomes or lysosomes that move along the axon in live hippocampal neurons
enzyme localization at high copper concentration. Deacidification prevents Cu-directed delivery to apical domain
under basal Cu2+ conditions, ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon
Cu2+-regulated, dileucine-dependent localization of ATP7B to the neuronal trans-Golgi network. Under basal Cu2+ conditions, ATP7B is localized to the trans-Golgi network and the plasma membrane of the soma and dendrites but not the axon. Addition of high Cu2+ concentrations cause loss of trans-Golgi network localization and somatodendritic polarity of ATP7B. ATP7B co-localizes with sigma1B, as well as with the endogenous gamma subunit at the trans-Golgi network
enzyme localization at low copper concentration
upon copper elevation, ATP7B moves from the trans-Golgi network to specialized vesicles, following copper depletion, ATP7B returns from vesicles to the trans-Golgi network
the dimeric structure is retained during ATP7B trafficking between the intracellular compartments
ATP7B incorporation into AP-1-containing clathrin-coated vesicles. Addition of high Cu2+ concentrations reduce ATP7B incorporation into AP-1-containing clathrin-coated vesicle
Cu induces an increase in the number of ATP7B vesicles, which traverse large basolateral endosomes en route to the apical domain
upon copper elevation, ATP7B moves from the trans-Golgi network to specialized vesicles, following copper depletion, ATP7B returns from vesicles to the trans-Golgi network
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
physiological function
additional information
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
Menkes disease results from loss-of-function mutations in ATP7A
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
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
ATP7A interacts with hundreds of proteins present in different compartments within cells
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
Fe uptake and efflux are impaired by Atp7a silencing
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
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
enzyme missense mutations are involved in Wilson's disease
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
physiological function
-
ATP7B is a copper dependent P-type ATPase, required for copper homeostasis
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
human Cu(I)-transporting ATPase ATP7B plays an essential role in maintaining cellular copper homeostasis. The enzyme transports copper to metalloenzymes undergoing functional maturation in this compartment. ATP hydrolysis supplies energy for copper transport. Upon copper elevation, enzyme ATP7B moves from the trans-Golgi network to specialized vesicles. In the vesicles, ATP7B sequesters excess copper for further export, which occurs via vesicle fusion at the plasma membrane. Following copper depletion, ATP7B returns from vesicles to the trans-Golgi network to resume its function in the biosynthesis of cuproenzymes. Role for domain dynamics in ATP7B trafficking
physiological function
the enzyme binds to the gamma-subunit of AP-1, an effector of polarized sorting in neurons, via dileucine-dependent binding of the C-terminal tail of ATP7B. Interaction with AP-1 is critical for somatodendritic polarity of ATP7B. Altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the sigma1A subunit isoform of AP-1
physiological function
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
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
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
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
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ATP7A_HUMAN
1500
7
163373
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
240000
and 480000, PAGE and gel filtration, streptavidin-tagged recombinant protein
480000
and 240000, PAGE and gel filtration, streptavidin-tagged recombinant protein
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
and monomer, 2 * 230000, streptavidin-tagged recombinant protein, calculated from sequence
monomer
and dimer, 1 * 230000, streptavidin-tagged recombinant protein, calculated from sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
NMR structure of metal-binding domain MBD1, shows the characteristic beta,alpha,beta,beta,alpha,beta ferredoxin fold. The copper binding motif CxxC appears to experience complex dynamics
structural model of a deletion mutant lacking the four N-terminal metal-binding domains
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C575A/C578A
-
mutation in the 6th copper site of the NMBD, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
C983A/C985A
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
additional information
C983A/C985A
-
mutation in the transmembrane copper binding site, TMBS, catalytically inactive, no phosphoenzyme intermediate formed upon addition of ATP
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in eukaryotic cells, human ATP7B forms dimers that can be purified following solubilization
recombinant His-tagged MBP-fusion enzyme from Escherichia coli by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression in rat intestinal epithelial IEC-6 cells, Atp7a protein expression is induced more strongly than mRNA in the duodenum of iron-deprived rats, real-time quantitative RT-PCR enzyme expression analysis
microsomes derived from COS-1 cells infected with adenovirus vector and expressing recombinant ATP7A/B
-
Recombinant adenovirus vector, rAdATP7Bmyc, containing CMV promoter driven WT human ATP7B cDNA, fused with 30 cmyc tag, expression in COS-1 cells
-
recombinant expression of His-tagged MBP-fusion enzyme in Escherichia coli, overexpression of GFP-tagged ATP7B in Rattus norvegicus hippocampal neurons, co-expression with myc-tagged wild-type or V98S-mutant sigma1A, with HA-tagged wild-type or V98S-mutant sigma1B, and with HA-tagged wild-type or V98S-mutant sigma1C
recombinant expression of the N-terminal domain of human ATP7B (N-ATP7B) fused to maltose-binding protein, and FLAG-tagged enzyme in HEK293T-Rex cells, co-expression of GFP-tagged nanoparticle in HEK-293T cells, the nanobodies bind to the distinct regions of N-ATP7B, binding sites of 2R50 and 2R51 are located within metal binding domains MBD1-4, revealing transient inter-domain interactions in N-ATP7B
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Atp7a expression is upregulated by iron chelation and copper loading. Recombinant Atp7a protein expression is induced more strongly than mRNA in the duodenum of iron-deprived rats, Atp7a expression is upregulated by iron chelation and copper loading, iron chelation increases Atp7a mRNA expression by 1.6fold, but has little effect on protein levels
copper has a direct influence on Atp7a protein expression independent of changes in mRNA levels
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
ATP7A protein is markedly downregulated in vessels isolated from type 2 diabetes mellitus patients. Akt2 (protein kinase B beta) activated by insulin promotes ATP7A stabilization via preventing ubiquitination/degradation as well as translocation to plasma membrane in vascular smooth muscle cells
analysis
method to probe Cu flow through human Atox1 and copper chaperone ATP7B proteins when expressed in yeast.
medicine
medicine
-
cisplatin-resistant cell sublines show cross-resistance to carboplatin and oxaliplatin. ATP7A expression in cisplatin-resistant cell sublines is much higher than in cisplatin-sensitive cell lines at both mRNA and protein levels. ATP7A-targeted siRNA in cisplatin-resistant cancer cells partially reverses cisplatin-resistance. It also increases cell apoptosis at different cisplatin concentrations
medicine
-
mutation T994I is located in the sixth transmembrane domain of ATP7A, and is associated with the an adult-onset isolated distal motor neuropathy, and with an abnormal interaction with p97/valosin-containing protein. T994I substitution results in conformational exposure of the UBX domain in the third lumenal loop of ATP7A, which then binds the N-terminal domain of p97/VCP. This abnormal interaction occurs at or near the cell plasma membrane
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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)
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)
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)
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)
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)
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)
EXTERNAL LINKS (specific for EC-Number 7.2.2.8)
Transporter Classification Database (TCDB): 3.A.3.5.19, 3.A.3.5.11, 3.A.3.5.32, 3.A.3.5.6, 3.A.3.5.3, 3.A.3.5.2, 3.A.3.5.5, 3.A.3.5.1, 3.A.3.5.29, 3.A.3.5.17, 3.A.3.5.7, 3.A.3.5.18, 3.A.3.5.41, 3.A.3.5.15, 3.A.3.5.37
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Release 2023.1 (January 2023)
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