InterPro domain: IPR005782

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 entry represent the P-type ATPase responsible for translocating calcium ions across the endoplasmic reticulum membrane of eukaryotes [ 8 ], and is of particular importance in the sarcoplasmic reticulum of skeletal and cardiac muscle in vertebrates [ 9 ]. These pumps transfer Ca2+ from the cytoplasm to the lumen of the endoplasmic reticulum. In humans and mice, at least, there are multiple isoforms of the SERCA pump with overlapping but not redundant functions. Defects in SERCA isoforms are associated with diseases in humans [ 10 ]. The calcium P-type ATPases have been characterised as Type IIA based on a phylogenetic analysis which distinguishes this group from the Type IIB PMCA calcium pump [ 11 ] described in IPR006408 . A separate analysis divides Type IIA into sub-types, SERCA and PMR1 [ 11 ] the latter of which is described in IPR006413 .

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. Sarco(endo)plasmic reticulum calcium pumps: recent advances in our understanding of structure/function and biology (review). Mol. Membr. Biol. 17, 189-200
9. SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility. J. Mol. Cell. Cardiol. 33, 1053-63
10. Ca2+ signalling and muscle disease. Eur. J. Biochem. 267, 5291-7
11. Two additional type IIA Ca(2+)-ATPases are expressed in Arabidopsis thaliana: evidence that type IIA sub-groups exist. Gene 236, 137-47