InterPro domain: IPR008250

P-ATPases (also known as E1-E2 ATPases) ([intenz:3.6.3.-]) are found in bacteria and in a number of eukaryotic plasma membranes and organelles [ 1 ]. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H ⁺ , Na ⁺ , K ⁺ , Mg ²⁺ , Ca ²⁺ , Ag ⁺ and Ag ²⁺ , Zn ²⁺ , Co ²⁺ , Pb ²⁺ , Ni ²⁺ , Cd ²⁺ , Cu ⁺ and Cu ²⁺ . P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [ 2 , 3 ]. The different types include:

• F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
• V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [ 4 ]. They are also found in bacteria [ 5 ].
• A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [ 6 , 7 ].
• P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
• E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.

This superfamily represents the actuator (A) domain, and some transmembrane helices found in P-type ATPases [ 8 ]. It contains the TGES-loop which is essential for the metal ion binding which results in tight association between the A and P (phosphorylation) domains [ 9 ]. It does not contain the phosphorylation site. It is thought that the large movement of the actuator domain, which is transmitted to the transmembrane helices, is essential to the long distance coupling between formation/decomposition of the acyl phosphate in the cytoplasmic P-domain and the changes in the ion-binding sites buried deep in the membranous region [ 10 ]. This domain has a modulatory effect on the phosphoenzyme processing steps through its nucleotide binding [ 11 ],[ 12 ].

1. Evolution of substrate specificities in the P-type ATPase superfamily. J. Mol. Evol. 46, 84-101
2. The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in function and changes in the H+/ATP coupling ratio. FEBS Lett. 576, 1-4
3. Mechanisms of ATPases--a multi-disciplinary approach. Curr. Protein Pept. Sci. 5, 89-105
4. Regulation and isoform function of the V-ATPases. Biochemistry 49, 4715-23
5. F-and V-ATPases in the genus Thermus and related species. Syst. Appl. Microbiol. 21, 12-22
6. New insights into structure-function relationships between archeal ATP synthase (A1A0) and vacuolar type ATPase (V1V0). Bioessays 30, 1096-109
7. F-type or V-type? The chimeric nature of the archaebacterial ATP synthase. Biochim. Biophys. Acta 1101, 232-5
8. Membrane topology of a P-type ATPase. The MgtB magnesium transport protein of Salmonella typhimurium. J. Biol. Chem. 268, 22469-79
9. Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues. Nature 432, 361-8
10. Critical interaction of actuator domain residues arginine 174, isoleucine 188, and lysine 205 with modulatory nucleotide in sarcoplasmic reticulum Ca2+-ATPase. J. Biol. Chem. 283, 35703-14
11. The structural basis of calcium transport by the calcium pump. Nature 450, 1036-42
12. Modulatory and catalytic modes of ATP binding by the calcium pump. EMBO J. 25, 2305-14