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Literature summary for 7.2.2.9 extracted from
- Mammalian copper-transporting P-type ATPases, ATP7A and ATP7B: emerging roles (2010), Int. J. Biochem. Cell Biol., 42, 206-209.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| 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 | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| Golgi membrane | ATP7A is found in the trans-Golgi network | Homo sapiens | 139 | - |
| melanosome | ATP7A | Homo sapiens | 42470 | - |
| secretory granule | ATP7A | Homo sapiens | 30141 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 165000 | - |
x * 180000, ATP7A, SDS-PAGE, x * 165000, ATP7B, SDS-PAGE | Homo sapiens |
| 180000 | - |
x * 180000, ATP7A, SDS-PAGE, x * 165000, ATP7B, SDS-PAGE | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + Cu2+/in | Mus musculus | - |
ADP + phosphate + Cu2+/out | - |
? |  |
| ATP + H2O + Cu2+/in | Homo sapiens | during the catalytic cycle of ATP7A/7B, cytosolic Cu is bound to an intramembrane CPC motif. The -phosphate of ATP is transferred to the invariant aspartate residue of the conserved DKTG motif, with formation of a transient acylphosphate intermediate. Cu is released on the other side of the membrane with concomitant dephosphorylation of aspartate, and the Cu-ATPase returns to its initial state | ADP + phosphate + Cu2+/out | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
genes ATP7A and ATP7B | - |
| Mus musculus | - |
genes ATP7A and ATP7B | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | ATP7A is widely expressed throughout the CNS | Homo sapiens | - |
| cerebellum | ATP7A and ATP7B | Mus musculus | - |
| hepatocyte | - |
Homo sapiens | - |
| intestine | ATP7A and ATP7B | Homo sapiens | - |
| kidney | ATP7A and ATP7B are co-expressed in proximal and distal epithelial cells | Homo sapiens | - |
| liver | ATP7A | Homo sapiens | - |
| retinal pigment epithelium | both Cu-ATPases ATP7A and ATP7B are expressed within retinal pigment epithelium | Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + Cu2+/in | - |
Mus musculus | ADP + phosphate + Cu2+/out | - |
? | |
| ATP + H2O + Cu2+/in | - |
Homo sapiens | ADP + phosphate + Cu2+/out | - |
? | |
| ATP + H2O + Cu2+/in | during the catalytic cycle of ATP7A/7B, cytosolic Cu is bound to an intramembrane CPC motif. The -phosphate of ATP is transferred to the invariant aspartate residue of the conserved DKTG motif, with formation of a transient acylphosphate intermediate. Cu is released on the other side of the membrane with concomitant dephosphorylation of aspartate, and the Cu-ATPase returns to its initial state | Homo sapiens | ADP + phosphate + Cu2+/out | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 180000, ATP7A, SDS-PAGE, x * 165000, ATP7B, SDS-PAGE | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ATP7A | - |
Mus musculus |
| ATP7A | - |
Homo sapiens |
| ATP7B | - |
Mus musculus |
| ATP7B | - |
Homo sapiens |
| copper-transporting P-type ATPase | - |
Mus musculus |
| copper-transporting P-type ATPase | - |
Homo sapiens |
| Cu-transporting P-type ATPase | - |
Mus musculus |
| Cu-transporting P-type ATPase | - |
Homo sapiens |
| More | ATP7A and ATP7B are members of the P1B-subfamily of the P-type ATPases | Mus musculus |
| More | ATP7A and ATP7B are members of the P1B-subfamily of the P-type ATPases | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | the catalytic cycle of ATP7A/7B is coupled to their intracellular trafficking, and these activities endow them with the biosynthetic and homeostatic functions that underlie the diverse range of physiological processes that depend upon their activities | Homo sapiens |
| additional information | mutations of ATP7A and ATP7B lead to the inherited disorders of Cu metabolism, Menkes and Wilson diseases. Disruption of ATP7B-mediated Cu export from liver hepatocytes into bile, and consequently liver and brain Cu accumulation. Elevation of Cu in vascular endothelial cells of the brains of MD patients indicates a role for this ATPase in Cu transport across the blood-brain barrier. ATP7A and ATP7B mediate resistance to anticancer drugs such as cis-diaminedichloroplatinum (II), i.e. cisplatin, by sequestration within intracellular compartments and potentially within the MBDs. Increased ATP7A/7B expression in a variety of clinical cancers and poorer survival rates following cisplatin-based chemotherapy, and between ATP7A upregulation and cancer metastasis | Homo sapiens |
| physiological function | ATP7A and ATP7B are two key proteins that regulate the Cu status of the body. They transport Cu across cellular membranes for biosynthetic and protective functions, enabling Cu to fulfill its role as a catalytic and structural cofactor for many essential enzymes, and to prevent a toxic build-up of Cu inside cells. A variety of regulatory mechanisms operate at transcriptional and post-translational levels to ensure adequate Cu supplies for both physiological and pathophysiological processes. ATP7B transports Cu across the apical surface implicating it as the major means of Cu secretion into milk during lactation. Both Cu-ATPases are expressed in the intestine and kidney and appear to have distinct but complementary functional roles. ATP7A is essential for dietary Cu absorption and mediates Cu transfer across the basolateral membrane of intestinal enterocytes into the portal circulation. ATP7B mayfine-tune intestinal Cu absorption, either via Cu excretion from the apical surface of enterocytes, and/or through vesicular sequestration of excess Cu in enterocytes that are regularly lost by shedding. In the kidney, ATP7A mediates Cu transport across the basolateral membrane for reabsorption into the blood and protection against Cu overload. Hence, ATP7A has a house-keeping role maintaining renal Cu homeostasis. ATP7B, which did not redistribute in response to Cu, more likely has a role in fine-tuning intracellular Cu balance through Cu storage in intracellular compartments | Homo sapiens |
| physiological function | ATP7A and ATP7B are two key proteins that regulate the Cu status of the body. They transport Cu across cellular membranes for biosynthetic and protective functions, enabling Cu to fulfill its role as a catalytic and structural cofactor for many essential enzymes, and to prevent a toxic build-up of Cu inside cells. A variety of regulatory mechanisms operate at transcriptional and post-translational levels to ensure adequate Cu supplies for both physiological and pathophysiological processes. In the cerebellum, Atp7a may have a homeostatic role maintaining intracellular Cu levels, while Atp7b has a biosynthetic role delivering Cu to enzymes such as ceruloplasmin. In retinal pigment epithelium ATP7A and ATP7B may control Cu transport to the outer retina, as well as Cu delivery to tyrosinase for melanogenesis within the retinal pigment epithelium, and to ceruloplasmin and hephaestin to maintain iron homeostasis | Mus musculus |
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Release 2023.1 (January 2023)
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