P-type ATPases

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Phosphorylation-type ATPases (EC 3.6.3.-) are associated with membranes and the transport of ions or phospholipids. Characteristics of the family are the transient phosphorylation of the transporters at an aspartate residue and the interconversion between E1 and E2 conformations in the activity cycle of the transporters, taken to represent ‘half-channels’ facing the cytoplasm and extracellular/luminal side of the membrane, respectively.

Sequence analysis across multiple species allows the definition of five subfamilies, P1-P5. The P1 subfamily includes heavy metal pumps, such as the copper ATPases. The P2 subfamily includes calcium, sodium/potassium and proton/potassium pumps. The P4 and P5 subfamilies include putative phospholipid flippases.

Na+/K+-ATPases

Overview

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The cell-surface Na+/K+-ATPase is an integral membrane protein which regulates the membrane potential of the cell by maintaining gradients of Na+ and K+ ions across the plasma membrane, also making a small, direct contribution to membrane potential, particularly in cardiac cells. For every molecule of ATP hydrolysed, the Na+/K+-ATPase extrudes three Na+ ions and imports two K+ ions. The active transporter is a heteromultimer with incompletely defined stoichiometry, possibly as tetramers of heterodimers, each consisting of one of four large, ten TM domain catalytic α subunits and one of three smaller, single TM domain glycoprotein β-subunits (see table). Additional protein partners known as FXYD proteins (e.g. FXYD2, P54710) appear to associate with and regulate the activity of the pump.

Transporters

α1 subunit Show summary » More detailed page

α2 subunit Show summary »

α3 subunit Show summary »

α4 subunit Show summary »

β1 subunit Show summary »

β2 subunit Show summary »

β3 subunit Show summary »

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Ca2+-ATPases

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The sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) is an intracellular membrane-associated pump for sequestering calcium from the cytosol into intracellular organelles, usually associated with the recovery phase following excitation of muscle and nerves.

The plasma membrane Ca2+-ATPase (PMCA) is a cell-surface pump for extruding calcium from the cytosol, usually associated with the recovery phase following excitation of cells. The active pump is a homodimer, each subunit of which is made up of ten TM segments, with cytosolic C- and N-termini and two large intracellular loops.

Secretory pathway Ca2+-ATPases (SPCA) allow accumulation of calcium and manganese in the Golgi apparatus.

Transporters

SERCA1 Show summary »

SERCA2 Show summary »

SERCA3 Show summary »

PMCA1 Show summary »

PMCA2 Show summary »

PMCA3 Show summary »

PMCA4 Show summary »

SPCA1 Show summary »

SPCA2 Show summary »

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H+/K+-ATPases

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The H+/K+ ATPase is a heterodimeric protein, made up of α and β subunits. The α subunit has 10 TM domains and exhibits catalytic and pore functions, while the β subunit has a single TM domain, which appears to be required for intracellular trafficking and stabilising the α subunit. The ATP4A and ATP4B subunits are expressed together, while the ATP12A subunit is suggested to be expressed with the β1 (ATP1B1) subunit of the Na+/K+-ATPase [8].

Transporters

ATP4A Show summary » More detailed page

ATP12A Show summary »

ATP4B Show summary »

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Cu+-ATPases

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Copper-transporting ATPases convey copper ions across cell-surface and intracellular membranes. They consist of eight TM domains and associate with multiple copper chaperone proteins (e.g. ATOX1, O00244).

Transporters

ATP7A Show summary »

ATP7B Show summary »

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Phospholipid-transporting ATPases

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These transporters are thought to translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from one side of the phospholipid bilayer to the other to generate asymmetric membranes. They are also proposed to be involved in the generation of vesicles from intracellular and cell-surface membranes.

Transporters

ATP8A1 Show summary »

ATP8A2 Show summary »

ATP8B1 Show summary »

ATP8B2 Show summary »

ATP8B3 Show summary »

ATP8B4 Show summary »

ATP9A Show summary »

ATP9B Show summary »

ATP10A Show summary »

ATP10B Show summary »

ATP10D Show summary »

ATP11A Show summary »

ATP11B Show summary »

ATP11C Show summary »

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References

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