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Literature summary for 7.2.2.9 extracted from

  • Leonhardt, K.; Gebhardt, R.; Moessner, J.; Lutsenko, S.; Huster, D.
    Functional interactions of Cu-ATPase ATP7B with cisplatin and the role of ATP7B in the resistance of cells to the drug (2009), J. Biol. Chem., 284, 7793-7802.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
cis-diamminedichloroplatinum DDP, stimulates catalytic phosphorylation of ATP7B Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
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 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information mutations of the first five N-terminal copper-binding sites of ATP7B do not inhibit the cisplatin-induced phosphorylation of ATP7B. In contrast, the deletion of the first four copper-binding sites abolishes the effect of cisplatin on the ATP7B activity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information in hepatocytes, ATP7B-mediated efflux does not play a major role in determining cell sensitivity to cis-diamminedichloroplatinum Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane ATP7B is a transmembrane protein Homo sapiens 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Cu+ Cu+ stimulates catalytic activity of ATP7B, inducing the hydrolysis of ATP via formation of an acyl-phosphate intermediate, a step necessary for subsequent transport of copper across membranes. Neither Cu2+ nor other divalent metals such as Zn2+ or Cd2+ stimulate the formation of phospho-intermediate Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O + Cu2+/in Homo sapiens ATP7B is a P1-type-ATPase with high selectivity to Cu+ ADP + phosphate + Cu2+/out
-
?
additional information Homo sapiens functional interactions between chemotherapeutic agent cisplatin and ATP7B, cisplatin binding to ATP7B and/or general changes in cellular copper homeostasis are likely contributors to the increased resistance to the drug ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein cisplatin, i.e. cis-diamminedichloroplatinum or DDP, stimulates catalytic phosphorylation of ATP7B Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant ATP7B from Spodoptera frugiperda Sf9 cell membranes Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
Hep-G2 cell trafficking of ATP7B in Hep-G2 cells is not regulated by cis-diamminedichloroplatinum, DDP, while Huh7 cells show a biphasic response with a sharp 50% decrease in cell survival Homo sapiens
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hepatocyte primary, ATP7B is highly expressed in hepatocytes Homo sapiens
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Huh-7 cell
-
Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O + Cu2+/in ATP7B is a P1-type-ATPase with high selectivity to Cu+ Homo sapiens ADP + phosphate + Cu2+/out
-
?
ATP + H2O + Cu2+/in Cu+ stimulates catalytic activity of ATP7B, inducing the hydrolysis of ATP via formation of an acyl-phosphate intermediate, a step necessary for subsequent transport of copper across membranes. Neither Cu2+ nor other divalent metals such as Zn2+ or Cd2+ stimulate the formation of phospho-intermediate Homo sapiens ADP + phosphate + Cu2+/out
-
?
additional information functional interactions between chemotherapeutic agent cisplatin and ATP7B, cisplatin binding to ATP7B and/or general changes in cellular copper homeostasis are likely contributors to the increased resistance to the drug Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
ATP7B
-
Homo sapiens
Cu-ATPase
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Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens