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== Introduction ==

All living organisms depend on P-type ATPase to pump cation across the membrane. They play a fundamental role in their metabolism and physiology. Ca2+ ATPase, a P-type ATPase, transports calcium ions across the membrane against a concentration gradient. These pumps clear cytoplasm of the second messenger, the calcium. It's very important to keep a low concentration of calcium in the cell for a good cell signaling.

We can found the PMCA (Plasma Membrane Ca2+ ATPase) which remove the calcium from the cell and the SERCA (Sarcoplasmic Endoplasmic Reticulum Ca2+ ATPase) which pumps calcium into the endoplasmic reticulum.

The hydrolysis of one adenosine triphosphate (ATP) is essential for the functioning of the pump and the transport of one calcium ion.

== Structural Highlights ==

== Ligand and Interaction ==

The architecture of calcium ATPase (determined by X-Ray crystallography) allow to understand mechanisms by which the energy of ATP is coupled to the calcium transport across a membrane.

To sum up, calcium pumps have two conformations, E1 and E2. These two conformations are characterized by different specificity for ion binding. When the pump is in the E1 state, it has high calcium affinity and interacts with calcium at one side of the membrane. In the E2 state, the enzyme has a lower calcium affinity and that leads to the release of the ion at the opposite side. E1 has the calcium binding site oriented toward the cytoplasm. E2 has the calcium binding site oriented toward the lumen of the endoplasmic reticulum or toward the extracellular background.  

== Biological Function and Localisation ==

Calcium is involved in many physiological processes such as programmed cell death, fertilization, gene transcription, secretion (including neurotransmitter secretion) etc. For example, the SERCA pump is mainly found in skeletal muscle cells and cardiac cells. It is involved in the relaxation of skeletal muscle cells. Those cells contain a special endoplasmic reticulum called the sarcoplasmic reticulum which is the place of calcium storage. After contraction, calcium ions are transported from the cytoplasm into the sarcoplasmic reticulum through the SERCA pump. This causes the relaxation of the muscle cells because the cytosolic concentration of calcium decreases. The SERCA pump works together with the PMCA pump to export calcium ions from the cytosol and to set the resting level of the cytosolic calcium concentration.  

== Regulations ==

There are different kind of calcium ATPase regulations. For example, the phospholamban (PLN or PLB) is a  membrane protein that regulates the calcium pump in cardiac muscle and skeletal muscle cells. This small phosphoprotein is a pentamer. The phospholamban can be phosphorylated at three distinct sites by various protein kinases (PKA, PKC, CamK...). The phosphorylation state is mediatedthrough beta-adrenergic stimulation. In unphosphorylate state, the phospholamban inhibits the activity of calcium pump in cardiac and skeletal muscle cells by decreasing the apparent affinity of the ATPase for calcium. The phosphorylation of the protein results in the dissociation of the protein from the ATPase. The phosphoprotein binds just downstream of the active ATPase site (asp351).

The activity of the calcium pump is also regulated by by calmodulin, acidic phospholipids and phosphorylation by kinases A and C. Most of the activation mechanisms implicate the C-terminal region of the pump containing the high affinity calmodulin binding domain, which is involved in the autoinhibition of the pump.

== Dysfunctions and Diseases ==