Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of an ATPase-coupled calcium transmembrane transporter activity. [GOC:BHF, GOC:rl, GOC:TermGenie, PMID:19708671]
Negative regulation of ATPase-coupled calcium transmembrane transporter activity encompasses the processes that diminish or inhibit the activity of transmembrane proteins responsible for transporting calcium ions across cellular membranes using the energy derived from ATP hydrolysis. These ATPase-coupled calcium transporters play a crucial role in maintaining calcium homeostasis within cells, influencing diverse cellular processes including muscle contraction, neurotransmitter release, and signal transduction.
The negative regulation of this activity can be achieved through various mechanisms:
1. **Phosphorylation:** Specific kinases can phosphorylate calcium transporter proteins, altering their conformation and reducing their affinity for calcium ions, thereby hindering their transport activity.
2. **Protein-Protein Interactions:** Regulatory proteins can bind to the calcium transporters, blocking their active sites or inhibiting their interaction with ATP, thus impeding their function.
3. **Calcium Binding Proteins:** Calcium-binding proteins like calmodulin can bind to the transporters and regulate their activity in a calcium-dependent manner. Increased intracellular calcium can trigger a feedback loop where these proteins bind to the transporters and reduce their activity, contributing to calcium homeostasis.
4. **Lipid Modifications:** Lipid modifications, such as palmitoylation, can alter the localization and function of calcium transporters within the cell membrane, potentially affecting their ability to transport calcium.
5. **Microenvironment Modulation:** Changes in the local pH or ionic composition surrounding the transporter can also influence its activity.
6. **Ubiquitination and Proteasomal Degradation:** Ubiquitination of the calcium transporters can target them for degradation by the proteasome, reducing their overall abundance and activity.
7. **Transcriptional Regulation:** The expression levels of genes encoding calcium transporters can be regulated by various transcription factors, affecting the overall number of these transporters in the cell.
These diverse mechanisms ensure a tightly regulated control over calcium transport activity, essential for maintaining cellular function and preventing imbalances that could lead to cellular dysfunction or disease.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Toll-like receptor 9 | A Toll-like receptor 9 that is encoded in the genome of human. [] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| hydroxychloroquine | hydroxychloroquine : An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions. Hydroxychloroquine: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) | aminoquinoline; organochlorine compound; primary alcohol; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; dermatologic drug |