Cloned (Comment) | Organism |
---|---|
rescue and correction of the Cu accumulation defect by expression of wild type MNK in non-polarized BHK cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | apical/subapical MNK distribution of the MNK L1487-1488A mutant | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | - |
Homo sapiens | 16020 | - |
membrane | - |
Saccharomyces cerevisiae | 16020 | - |
additional information | mechanisms for copper-ATPase trafficking, detailed overview | Homo sapiens | - |
- |
additional information | mechanisms for copper-ATPase trafficking, detailed overview | Saccharomyces cerevisiae | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O + Cu2+/in | Saccharomyces cerevisiae | - |
ADP + phosphate + Cu2+/out | - |
? | |
ATP + H2O + Cu2+/in | Homo sapiens | the copper-translocating Menkes, ATP7A or MNK protein, and Wilson, ATP7B or WND protein, P-type ATPases are pivotal for copper homeostasis, functioning in the biosynthetic incorporation of Cu into copper-dependent enzymes of the secretory pathway, Cu detoxification via Cu efflux, and specialized roles such as MNK in systemic Cu absorption and WND in Cu excretion. MNK and WND Cu-ATPases translocate Cu across biological membranes, MNK participates in vectorial Cu transport across the basolateral membrane and into the bloodstream. Phosphorylation events play a central role in Cu homeostasis, promoting multi-layered regulation and cross-talk between cuproenzymes and Cu-independent mechanisms, overview. MNK is responsible for direct Cu export in response to lactation, where hormonal induction by estrogen, progesterone, insulin and prolactin stimulate the expression and basolateral localization of MNK and the Cu uptake protein Ctr1 to perform a homeostatic function in the mothers tissue | ADP + phosphate + Cu2+/out | - |
? | |
additional information | Homo sapiens | both Menkes and Wilson Disease are severe inherited human diseases involving dysfunctional Cu homeostasis, caused by mutations in the ATP7A and ATP7B genes, respectively. MNK function is linked to activation of the N-methyl-D-aspartic, NMDA, receptor by glycine-glutamate stimulating synaptic release of intracellular Cu, where upon NMDA activation MNK undergoes rapid, reversible relocalization from the TGN to post-Golgi neuronal processes for Cu release. Role for WND in apical Cu excretion and storage in Cu-loaded vesicles, whereas Cu-stimulated MNK trafficking from internal secretory compartments to the basolateral membrane aids Cu re-absorption | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Saccharomyces cerevisiae | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | both MNK and WND are phosphorylated on serine residues, indicating a key role for one or more serine/threonine kinases for regulation of their trafficking and possibly function | Homo sapiens |
phosphoprotein | Ccc2 N-terminal phosphorylation may be coupled to the ATPase domain catalytic cycle. Protein kinase A phosphorylation site at Ser258 is located between MBD6 and the first transmembrane domain, Cu is predicted to promote Ser258 phosphorylation by increasing solvent accessibility of the region as a consequence of Cu-MBD interactions | Saccharomyces cerevisiae |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
enterocyte | - |
Homo sapiens | - |
fibroblast | - |
Homo sapiens | - |
hippocampus | - |
Homo sapiens | - |
mammary gland | - |
Homo sapiens | - |
neuron | hippocampal, neuronal MNK trafficking may occur independently of its catalytic cycle | Homo sapiens | - |
placenta | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + H2O + Cu2+/in | - |
Homo sapiens | ADP + phosphate + Cu2+/out | - |
? | |
ATP + H2O + Cu2+/in | - |
Saccharomyces cerevisiae | ADP + phosphate + Cu2+/out | - |
? | |
ATP + H2O + Cu2+/in | the copper-translocating Menkes, ATP7A or MNK protein, and Wilson, ATP7B or WND protein, P-type ATPases are pivotal for copper homeostasis, functioning in the biosynthetic incorporation of Cu into copper-dependent enzymes of the secretory pathway, Cu detoxification via Cu efflux, and specialized roles such as MNK in systemic Cu absorption and WND in Cu excretion. MNK and WND Cu-ATPases translocate Cu across biological membranes, MNK participates in vectorial Cu transport across the basolateral membrane and into the bloodstream. Phosphorylation events play a central role in Cu homeostasis, promoting multi-layered regulation and cross-talk between cuproenzymes and Cu-independent mechanisms, overview. MNK is responsible for direct Cu export in response to lactation, where hormonal induction by estrogen, progesterone, insulin and prolactin stimulate the expression and basolateral localization of MNK and the Cu uptake protein Ctr1 to perform a homeostatic function in the mothers tissue | Homo sapiens | ADP + phosphate + Cu2+/out | - |
? | |
ATP + H2O + Cu2+/in | Ccc2 N-terminal phosphorylation may be coupled to the ATPase domain catalytic cycle | Saccharomyces cerevisiae | ADP + phosphate + Cu2+/out | - |
? | |
additional information | both Menkes and Wilson Disease are severe inherited human diseases involving dysfunctional Cu homeostasis, caused by mutations in the ATP7A and ATP7B genes, respectively. MNK function is linked to activation of the N-methyl-D-aspartic, NMDA, receptor by glycine-glutamate stimulating synaptic release of intracellular Cu, where upon NMDA activation MNK undergoes rapid, reversible relocalization from the TGN to post-Golgi neuronal processes for Cu release. Role for WND in apical Cu excretion and storage in Cu-loaded vesicles, whereas Cu-stimulated MNK trafficking from internal secretory compartments to the basolateral membrane aids Cu re-absorption | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ATP7A | - |
Homo sapiens |
ATP7B | - |
Homo sapiens |
Ccc2 | - |
Saccharomyces cerevisiae |
copper translocating P-type ATPase | - |
Homo sapiens |
copper-ATPase | - |
Saccharomyces cerevisiae |
copper-translocating Menkes P-type ATPase | - |
Homo sapiens |
copper-translocating Wilson P-type ATPase | - |
Homo sapiens |
Cu-ATPase | - |
Saccharomyces cerevisiae |
MNK | - |
Homo sapiens |
MNK Cu-ATPase | - |
Homo sapiens |
WND | - |
Homo sapiens |
WND Cu-ATPase | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens | |
ATP | - |
Saccharomyces cerevisiae |