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128  structures 3559  species 9  interactions 13024  sequences 278  architectures

Family: Cation_ATPase_C (PF00689)

Summary: Cation transporting ATPase, C-terminus

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "P-type ATPase". More...

P-type ATPase Edit Wikipedia article

1wpg opm.png
Calcium ATPase, E2-Pi state
Symbol E1-E2_ATPase
Pfam PF00122
InterPro IPR008250
SCOP 1su4
TCDB 3.A.3
OPM superfamily 22
OPM protein 3b9b

The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases fall under the P-type ATPase (P-ATPase) Superfamily (TC# 3.A.3) which, as of early 2016, includes 20 different protein families. P-type ATPases are α-helical bundle primary transporters named based upon their ability to catalyze auto- (or self-) phosphorylation of a key conserved aspartate residue within the pump and their energy source, adenosine triphosphate (ATP). In addition, they all appear to interconvert between at least two different conformations, denoted by E1 and E2.

Most members of this transporter superfamily catalyze cation uptake and/or efflux, however one subfamily (TC# 3.A.3.8) is involved in flipping phospholipids to maintain the asymmetric nature of the biomembrane.

Prominent examples of P-type ATPases are the sodium-potassium pump (Na+/K+-ATPase), the plasma membrane proton pump (H+-ATPase), the proton-potassium pump (H+/K+-ATPase), and the calcium pump (Ca2+-ATPase).


The first P-type ATPase discovered was the Na+/K+-ATPase, which Nobel laureate Jens Christian Skou isolated in 1957.[1] The Na+/K+-ATPase was only the first member of a large and still-growing protein family (see Swiss-Prot Prosite motif PS00154).

Phylogenetic classification

The Transporter Classification Database provides a representative list of members of the P-ATPase superfamily, which as of early 2016 consisting of 20 families. Members of the P-ATPase superfamily are found in bacteria, archaea and eukaryotes. Clustering on the phylogenetic tree is usually in accordance with specificity for the transported ion(s).

In eukaryotes, they are present in the plasma membranes or endoplasmic reticular membranes. In prokaryotes, they are localized to the cytoplasmic membranes.

P-type ATPases from 26 eukaryotic species were analyzed later.[2] [3]

Chan et al., (2010) conducted an equivalent but more extensive analysis of the P-type ATPase Superfamily in Prokaryotes and compared them with those from Eukaryotes. While some families are represented in both types of organisms, others are found only in one of the other type. The primary functions of prokaryotic P-type ATPases appear to be protection from environmental stress conditions. Only about half of the P-type ATPase families are functionally characterized.[4]


A phylogenetic analysis of 159 sequences made in 1998 by Axelsen and Palmgren suggested that P-type ATPases can be divided into five subfamilies (types), based strictly on a conserved sequence kernel excluding the highly variable N and C terminal regions.[5] Chan et al. (2010) also analyzed P-type ATPases in all major prokaryotic phyla for which complete genome sequence data were available and compared the results with those for eukaryotic P-type ATPases.[6] The phylogenetic analysis grouped the proteins independent of the organism from which they are isolated and showed that the diversification of the P-type ATPase family occurred prior to the separation of eubacteria, archaea, and eucaryota. This underlines the significance of this protein family for cell survival under stress conditions.[5]

  • Type I consists of the transition/heavy metal ATPases. Topological type I (heavy metal) P-type ATPases predominate in prokaryotes (approx. tenfold).[2]
    • Type IA ATPases are involved in K+ import (TC# 3.A.3.7). They are atypical P-type ATPases because, unlike other P-type ATPases, they function as part of a heterotetrameric complex (called KdpFABC), where the actual K+ transport is mediated by another subcomponent of the complex.
    • Type IB ATPases are involved in transport of the soft Lewis acids: Cu+, Ag+, Cu2+, Zn2+, Cd2+, Pb2+ and Co2+ (TC#s 3.A.3.5 and 3.A.3.6). They are key elements for metal resistance and metal homeostasis in a wide range of organisms.
  • Type II ATPases are split into four groups. Topological type II ATPases (specific for Na+,K+, H+ Ca2+, Mg2+ and phospholipids) predominate in eukaryotes (approx. twofold).[2]
    • Type IIA transports Ca2+. SERCA1a is a type IIA pump. (TC# 3.A.3.2)
    • Type IIB transports Ca2+. (TC# 3.A.3.2)
    • Type IIC consists of the closely related Na+/K+ and H+/K+ ATPases from animal cells. (TC# 3.A.3.1)
    • Type IID contains a small number of fungal ATPases of unknown function. (Fungal K+ transporters; TC# 3.A.3.9)
  • Type III ATPases contains the plasma membrane H+-ATPases from plants and fungi (IIIA) and a small subdivision with Mg2+-ATPases from three bacterial species (IIIB). Fungal H+ transporters (TC# 3.A.3.3) and Mg2+ (TC# 3.A.3.4)
  • Type IV ATPases have been shown to be involved in the transport of phospholipids,[7] such as phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine.[8]
  • Type V ATPases have unknown specificity. This large group is found only in eukaryotes and is believed to be involved in cation transport in the endoplasmic reticulum.

In addition, several prokaryotic families of unknown function have been identified.[4]

Horizontal Gene Transfer

Many P-type ATPase families are found exclusively in prokaryotes (e.g. Kdp-type K+ uptake ATPases (type III) and all prokaryotic functionally uncharacterized P-type ATPase (FUPA) families), while others are restricted to eukaryotes (e.g. phospholipid flippases and all 13 eukaryotic FUPA families).[2] Horizontal gene transfer has occurred frequently among bacteria and archaea, which have similar distributions of these enzymes, but rarely between most eukaryotic kingdoms, and even more rarely between eukaryotes and prokaryotes. In some bacterial phyla (e.g. Bacteroidetes, Flavobacteria and Fusobacteria), ATPase gene gain and loss as well as horizontal transfer occurred seldom in contrast to most other bacterial phyla. Some families (i.e., Kdp-type ATPases) underwent far less horizontal gene transfer than other prokaryotic families, possibly due to their multisubunit characteristics. Functional motifs are better conserved across family lines than across organismal lines, and these motifs can be family specific, facilitating functional predictions. In some cases, gene fusion events created P-type ATPases covalently linked to regulatory catalytic enzymes. In one family (FUPA Family 24), a type I ATPase gene (N-terminal) is fused to a type II ATPase gene (C-terminal) with retention of function only for the latter. Genome minimalization led to preferential loss of P-type ATPase genes. Chan et al. (2010) suggested that in prokaryotes and some unicellular eukaryotes, the primary function of P-type ATPases is protection from extreme environmental stress conditions. The classification of P-type ATPases of unknown function into phylogenetic families provides guides for future molecular biological studies.[6]


Many of these protein complexes are multisubunit with a large subunit serving the primary ATPase and ion translocation functions. Many eukaryotic P-type ATPases are monomeric or homodimeric enzymes of the catalytic subunit that hydrolyzes ATP. They contain the aspartyl phosphorylation site and catalyzes ion transport. The Na+/K+-ATPases, the Ca2+-ATPases and the (fungal) H+-ATPases of higher organisms exhibit 10 transmembrane α helical spanners (TMSs), some of them highly tilted. Additional subunits that appear to lack catalytic activity may be present in the ATPase complex.


The X-ray crystal structure at 3.5 Å resolution of the pig renal Na+/K+-ATPase has been determined with two rubidium ions bound in an occluded state in the transmembrane part of the α-subunit.[9] Several of the residues forming the cavity for rubidium/potassium occlusion in the Na+/K+-ATPase are homologous to those binding calcium in the Ca2+-ATPase of the sarco(endo)plasmic reticulum. The carboxy terminus of the α-subunit is contained within a pocket between transmembrane helices and seems to be a novel regulatory element controlling sodium affinity, possibly influenced by the membrane potential.

Crystal Structures are available in RCSB and include: PDB: 4RES​, 4RET​, 3WGU​, 3WGV​, among others.[10]

Ca2+ ATPase

Structures are available for both the E1 and E2 states of the Ca2+ ATPase showing that Ca2+ binding induces major changes in all three cytoplasmic domains relative to each other.[11] Xu et al. proposed how Ca2+ binding induces conformational changes in TMS 4 and 5 in the membrane domain (M) that in turn induce rotation of the phosphorylation domain (P).[11] The nucleotide binding (N) and β-sheet (β) domains are highly mobile, with N flexibly linked to P, and β flexibly linked to M. Modeling of the fungal H+ ATPase, based on the structures of the Ca2+ pump, suggested a comparable 70º rotation of N relative to P to deliver ATP to the phosphorylation site.[12]

One report suggests that this sarcoplasmic reticulum (SR) Ca2+ ATPase is homodimeric.[13]

Crystal structures have shown that the conserved TGES loop of the Ca2+-ATPase is isolated in the Ca2E1 state but becomes inserted in the catalytic site in E2 states.[14] Anthonisen et al. (2006) characterized the kinetics of the partial reaction steps of the transport cycle and the binding of the phosphoryl analogs BeF, AlF, MgF, and vanadate in mutants with alterations to conserved TGES loop residues. The data provide functional evidence supporting a role of Glu183 in activating the water molecule involved in the E2P → E2 dephosphorylation and suggest a direct participation of the side chains of the TGES loop in the control and facilitation of the insertion of the loop in the catalytic site. The interactions of the TGES loop furthermore seem to facilitate its disengagement from the catalytic site during the E2 → Ca2E1 transition.[14]

Crystal Structures of Calcium ATPase are available in RCSB and include: PDB: 4AQR​, 2L1W​, 2M7E​, 2M73​, among others.[15]


Most of our knowledge about the structure and function of P-type ATPases originates from SERCA1a, a sarco(endo)plasmic reticulum Ca2+-ATPase of fast twitch muscle from adult rabbit. It is generally acknowledged that the structure of SERCA1a is representative for the superfamily of P-type ATPases.[16]

SERCA1a is composed of a cytoplasmic section and a transmembrane section with two Ca2+-binding sites. The cytoplasmic section consists of three cytoplasmic domains, designated the P, N, and A domains, containing over half the mass of the protein. The transmembrane section has ten transmembrane helices (M1-M10), with the two Ca2+-binding sites located near the midpoint of the bilayer. The binding sites are formed by side-chains and backbone carbonyls from M4, M5, M6, and M8. M4 is unwound in this region due to a conserved proline (P308). This unwinding of M4 is recognised as a key structural feature of P-type ATPases.

The P domain contains the canonical aspartic acid phosphorylated during the reaction cycle. It is composed of two parts widely separated in sequence. These two parts assemble into a seven-strand parallel β-sheet with eight short associated a-helices, forming a Rossmann fold.

The N domain is inserted between the two segments of the P domain, and is formed of a seven-strand antiparallel β-sheet between two helix bundles. This domain contains the ATP-binding pocket, pointing out toward the solvent near the P-domain.

The A domain is the smallest of the three domains. It consists of a distorted jellyroll structure and two short helices. It is the actuator domain modulating the occlusion of Ca2+ in the transmembrane binding sites, and it is pivot in transposing the energy from the hydrolysis of ATP in the cytoplasmic domains to the vectorial transport of cations in the transmembrane domain. The A domain dephosphorylates the P domain as part of the reaction cycle using a highly conserved TGES motif located at one end of the jellyroll.

ATP hydrolysis occurs in the cytoplasmic headpiece at the interface between domain N and P. Two Mg-ion sites form part of the active site. ATP hydrolysis is tightly coupled to Ca2+ translocation through the membrane, more than 40 Å away, by the A domain.[17]

It is interesting to note that the folding pattern and the locations of the critical amino acids for phosphorylation in P-type ATPases has the haloacid dehalogenase fold characteristic of the haloacid dehalogenase (HAD) superfamily, as predicted by sequence homology. The HAD superfamily functions on the common theme of an aspartate ester formation by an SN2 reaction mechanism. This SN2 reaction is clearly observed in the solved structure of SERCA with ADP plus AlF4.[18]

Crystal structures of Sarcoplasimc/endoplasmic reticulum ATP driven calcium pumps can be found in RCSB.[19]

Differences from SERCA1a

Various subfamilies of P-type ATPases also need additional subunits for proper function. Both P-type IA and P- type IV pumps needs extra subunits to function. The functional unit of Na+/K+-ATPase consists of two additional subunits, beta and gamma, involved in trafficking, folding, and regulation of these pumps. SERCA1a and other P-IIA ATPases are also regulated by phospholamban and sarcolipin in vivo. It is presumed that other subfamilies need additional subunits for the proper function in vivo, also.

Some members of the family have additional domains fused to the pump. Heavy metal pumps can have several N- and C-terminal heavy metal-binding domains that have been found to be involved in regulation.

The proton pumps (IIIA) have a C-terminal regulatory domain (called the R domain), which, when unphosphorylated, inhibit pumping.

While most subfamilies have 10 transmembrane helices, there are some notable exceptions. The P-type IA ATPases are predicted to have 7, and the large subfamily of heavy metal pumps (type IB) is predicted to have 8 transmembrane helices. Type V appears to have a total of 12 transmembrane helices.


This type of proton pumps was found in plasma membrane of plants and yeast. It maintains the level of intracellular pH and transmembrane potential.[20] Ten transmembrane helices and three cytoplasmic domains define the functional unit of ATP-coupled proton transport across the plasma membrane, and the structure is locked in a functional state not previously observed in P-type ATPases. The transmembrane domain reveals a large cavity, which is likely to be filled with water, located near the middle of the membrane plane where it is lined by conserved hydrophilic and charged residues. Proton transport against a high membrane potential is readily explained by this structural arrangement.[21]


P-type ATPases participate in nerve impulse, relaxation of muscles, secretion and absorption in the kidney, absorption of nutrient in the intestine and other physiological processes.

All P-type ATPases use the energy derived from ATP to drive transport. They generally form a high-energy aspartyl-phosphoanhydride intermediate in the reaction cycle, and they interconvert between at least two different conformations, denoted by E1 and E2. The E1-E2 notation stems from the initial studies on this family of enzymes made on the Na+/K+-ATPase, where the sodium form and the potassium form are referred to as E1 and E2, respectively, in the "Post-Albers scheme". The E1-E2 schema has been proven to work, but there exist more than two major conformational states. The E1-E2 notation highlights the selectivity of the enzyme. In E1, the pump has high affinity for the exported substrate and low affinity for the imported substrate. In E2, it has low affinity of the exported substrate and high affinity for the imported substrate. Four major enzyme states form the cornerstones in the reaction cycle. Several additional reaction intermediates occur interposed. These are termed E1~P, E2P, E2-P*, and E1/E2.[22]

Calcium ATPase

In the case of SERCA1a, energy from ATP is used to transport 2 Ca2+-ions from the cytoplasmic side to the lumen of the sarcoplasmatic reticulum, and to countertransport 1-3 protons into the cytoplasm. Starting in the E1/E2 state, the reaction cycle begins as the enzyme releases 1-3 protons from the cation-ligating residues, in exchange for cytoplasmic Ca2+-ions. This leads to assembly of the phosphorylation site between the ATP-bound N domain and the P domain, while the A domain directs the occlusion of the bound Ca2+. In this occluded state, the Ca2+ ions are buried in a proteinaceous environment with no access to either side of the membrane.The Ca2E1~P state becomes formed through a kinase reaction, where the P domain becomes phosphorylated, producing ADP. The cleavage of the β-phosphodiester bond releases the gamma-phosphate from ADP and unleashes the N domain from the P domain.

This then allows the A domain to rotate toward the phosphorylation site, making a firm association with both the P and the N domains. This movement of the A domain exerts a downward push on M3-M4 and a drag on M1-M2, forcing the pump to open at the luminal side and forming the E2P state. During this transition, the transmembrane Ca2+-binding residues are forced apart, destroying the high-affinity binding site. This is in agreement with the general model form substrate translocation, showing that energy in primary transport is not used to bind the substrate but to release it again from the buried counter ions. At the same time the N domain becomes exposed to the cytosol, ready for ATP exchange at the nucleotide-binding site.

As the Ca2+ dissociate to the luminal side, the cation binding sites are neutralised by proton binding, which makes a closure of the transmembrane segments favourable. This closure is coupled to a downward rotation of the A domain and a movement of the P domain, which then leads to the E2-P* occluded state. Meanwhile, the N domain exchanges ADP for ATP.

The P domain is dephosphorylated by the A domain, and the cycle completes when the phosphate is released from the enzyme, stimulated by the newly bound ATP, while a cytoplasmic pathway opens to exchange the protons for two new Ca2+-ions.[22]

Copper ATPase

Metal binding to transmembrane metal-binding sites (TM-MBS) in Cu+-ATPases is required for enzyme phosphorylation and subsequent transport. However, Cu+ does not access Cu+-ATPases in a free (hydrated) form but is bound to a chaperone protein. The delivery of Cu+ by Archaeoglobus fulgidus Cu+-chaperone, CopZ (see TC# 3.A.3.5.7), to the corresponding Cu+-ATPase, CopA (TC# 3.A.3.5.30), has been studied.[23] CopZ interacted with and delivered the metal to the N-terminal metal binding domain(s) of CopA (MBDs). Cu+-loaded MBDs, acting as metal donors, were unable to activate CopA or a truncated CopA lacking MBDs. Conversely, Cu+-loaded CopZ activated the CopA ATPase and CopA constructs in which MBDs were rendered unable to bind Cu+. Furthermore, under nonturnover conditions, CopZ transferred Cu+ to the TM-MBS of a CopA lacking MBDs altogether. Thus, MBDs may serve a regulatory function without participating directly in metal transport, and the chaperone delivers Cu+ directly to transmembrane transport sites of Cu+-ATPases.[23] Wu et al. (2008) have determined structures of two constructs of the Cu (CopA) pump from Archaeoglobus fulgidus by cryoelectron microscopy of tubular crystals, which revealed the overall architecture and domain organization of the molecule. They localized its N-terminal MBD within the cytoplasmic domains that use ATP hydrolysis to drive the transport cycle and built a pseudoatomic model by fitting existing crystallographic structures into the cryoelectron microscopy maps for CopA. The results also similarly suggested a Cu-dependent regulatory role for the MBD.[24]

In the Archaeoglobus fulgidus CopA (TC# 3.A.3.5.7), invariant residues in helixes 6, 7 and 8 form two transmembrane metal binding sites (TM-MBSs). These bind Cu+ with high affinity in a trigonal planar geometry. The cytoplasmic Cu+ chaperone CopZ transfers the metal directly to the TM-MBSs; however, loading both of the TM-MBSs requires binding of nucleotides to the enzyme. In agreement with the classical transport mechanism of P-type ATPases, occupancy of both transmembrane sites by cytoplasmic Cu+ is a requirement for enzyme phosphorylation and subsequent transport into the periplasmic or extracellular milieu. Transport studies have shown that most Cu+-ATPases drive cytoplasmic Cu+ efflux, albeit with quite different transport rates in tune with their various physiological roles. Archetypical Cu+-efflux pumps responsible for Cu+ tolerance, like the Escherichia coli CopA, have turnover rates ten times higher than those involved in cuproprotein assembly (or alternative functions). This explains the incapability of the latter group to significantly contribute to the metal efflux required for survival in high copper environments. Structural and mechanistic details of copper-transporting P-type ATPase functionhave been described.[25]

General transport reaction

The generalized reaction for P-type ATPases is:

nMe1 (out) + mMe2 (in) + ATP → nMe1 (in) + mMe2 (out) + ADP + Pi.

where Me=Metal

Human genes

Human genes encoding P-type ATPases or P-type ATPase-like proteins include:

See also


  1. ^ SKOU JC (February 1957). "The influence of some cations on an adenosine triphosphatase from peripheral nerves". Biochim. Biophys. Acta. 23 (2): 394–401. PMID 13412736. doi:10.1016/0006-3002(57)90343-8. 
  2. ^ a b c d Thever, Mark D.; Jr, Milton H. Saier (2009-06-23). "Bioinformatic Characterization of P-Type ATPases Encoded Within the Fully Sequenced Genomes of 26 Eukaryotes". Journal of Membrane Biology. 229 (3): 115–130. ISSN 0022-2631. PMC 2709905Freely accessible. PMID 19548020. doi:10.1007/s00232-009-9176-2. 
  3. ^ Rodríguez-Navarro, Alonso; Benito, Begoña (2010-10-01). "Sodium or potassium efflux ATPase: A fungal, bryophyte, and protozoal ATPase". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1798 (10): 1841–1853. doi:10.1016/j.bbamem.2010.07.009. 
  4. ^ a b Chan, Henry; Babayan, Vartan; Blyumin, Elya; Gandhi, Charmy; Hak, Kunal; Harake, Danielle; Kumar, Kris; Lee, Perry; Li, Tze T. (2010-01-01). "The p-type ATPase superfamily". Journal of Molecular Microbiology and Biotechnology. 19 (1–2): 5–104. ISSN 1660-2412. PMID 20962537. doi:10.1159/000319588. 
  5. ^ a b Axelsen KB, Palmgren MG (January 1998). "Evolution of substrate specificities in the P-type ATPase superfamily". J. Mol. Evol. 46 (1): 84–101. PMID 9419228. doi:10.1007/PL00006286. 
  6. ^ a b Chan, Henry; Babayan, Vartan; Blyumin, Elya; Gandhi, Charmy; Hak, Kunal; Harake, Danielle; Kumar, Kris; Lee, Perry; Li, Tze T. (2010). "The P-Type ATPase Superfamily". Journal of Molecular Microbiology and Biotechnology. 19 (1–2): 5–104. PMID 20962537. doi:10.1159/000319588. 
  7. ^ Lenoir G, Williamson P, Holthuis JC (December 2007). "On the origin of lipid asymmetry: the flip side of ion transport". Curr Opin Chem Biol. 11 (6): 654–61. PMID 17981493. doi:10.1016/j.cbpa.2007.09.008. 
  8. ^ Lopez-Marques RL, Poulsen LR, Hanisch S, Meffert K, Buch-Pedersen MJ, Jakobsen MK, Pomorski TG, Palmgren MG (2010). "Intracellular targeting signals and lipid specificity determinants of the ALA/ALIS P4-ATPase complex reside in the catalytic ALA alpha-subunit". Mol Biol Cell. 21 (5): 791–801. PMC 2828965Freely accessible. PMID 20053675. doi:10.1091/mbc.E09-08-0656. 
  9. ^ Morth, J. Preben; Pedersen, Bjørn P.; Toustrup-Jensen, Mads S.; Sørensen, Thomas L.-M.; Petersen, Janne; Andersen, Jens Peter; Vilsen, Bente; Nissen, Poul (2007-12-13). "Crystal structure of the sodium-potassium pump". Nature. 450 (7172): 1043–1049. ISSN 1476-4687. PMID 18075585. doi:10.1038/nature06419. 
  10. ^
  11. ^ a b Xu, Chen; Rice, William J.; He, Wanzhong; Stokes, David L. (2002-02-08). "A structural model for the catalytic cycle of Ca(2+)-ATPase". Journal of Molecular Biology. 316 (1): 201–211. ISSN 0022-2836. PMID 11829513. doi:10.1006/jmbi.2001.5330. 
  12. ^ Kühlbrandt, Werner; Zeelen, Johan; Dietrich, Jens (2002-09-06). "Structure, mechanism, and regulation of the Neurospora plasma membrane H+-ATPase". Science. 297 (5587): 1692–1696. ISSN 1095-9203. PMID 12169656. doi:10.1126/science.1072574. 
  13. ^ Ushimaru, Makoto; Fukushima, Yoshihiro (2008-09-15). "The dimeric form of Ca2+-ATPase is involved in Ca2+ transport in the sarcoplasmic reticulum". The Biochemical Journal. 414 (3): 357–361. ISSN 1470-8728. PMID 18471093. doi:10.1042/BJ20071701. 
  14. ^ a b Anthonisen, Anne Nyholm; Clausen, Johannes D.; Andersen, Jens Peter (2006-10-20). "Mutational analysis of the conserved TGES loop of sarcoplasmic reticulum Ca2+-ATPase". The Journal of Biological Chemistry. 281 (42): 31572–31582. ISSN 0021-9258. PMID 16893884. doi:10.1074/jbc.M605194200. 
  15. ^
  16. ^ Stokes DL, Green NM (2003). "Structure and function of the calcium pump". Annu Rev Biophys Biomol Struct. 32: 445–68. PMID 12598367. doi:10.1146/annurev.biophys.32.110601.142433. 
  17. ^ Toyoshima C, Nakasako M, Nomura H, Ogawa H (June 2000). "Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution". Nature. 405 (6787): 647–55. PMID 10864315. doi:10.1038/35015017. 
  18. ^ PDB: 1T5T​; Sørensen TL, Møller JV, Nissen P (June 2004). "Phosphoryl transfer and calcium ion occlusion in the calcium pump". Science. 304 (5677): 1672–5. PMID 15192230. doi:10.1126/science.1099366. 
  19. ^
  20. ^ Kühlbrandt, Werner; Zeelen, Johan; Dietrich, Jens (2002-09-06). "Structure, Mechanism, and Regulation of the Neurospora Plasma Membrane H+-ATPase". Science. 297 (5587): 1692–1696. ISSN 0036-8075. PMID 12169656. doi:10.1126/science.1072574. 
  21. ^ Pedersen, Bjørn P.; Buch-Pedersen, Morten J.; Preben Morth, J.; Palmgren, Michael G.; Nissen, Poul (2007-12-13). "Crystal structure of the plasma membrane proton pump". Nature. 450 (7172): 1111–1114. ISSN 0028-0836. PMID 18075595. doi:10.1038/nature06417. 
  22. ^ a b Olesen C, Picard M, Winther AM, et al. (December 2007). "The structural basis of calcium transport by the calcium pump". Nature. 450 (7172): 1036–42. PMID 18075584. doi:10.1038/nature06418. 
  23. ^ a b González-Guerrero, Manuel; Argüello, José M. (2008-04-22). "Mechanism of Cu+-transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites". Proceedings of the National Academy of Sciences of the United States of America. 105 (16): 5992–5997. ISSN 1091-6490. PMC 2329688Freely accessible. PMID 18417453. doi:10.1073/pnas.0711446105. 
  24. ^ Wu, Chen-Chou; Rice, William J.; Stokes, David L. (2008-06-01). "Structure of a copper pump suggests a regulatory role for its metal-binding domain". Structure (London, England: 1993). 16 (6): 976–985. ISSN 0969-2126. PMC 2705936Freely accessible. PMID 18547529. doi:10.1016/j.str.2008.02.025. 
  25. ^ Meng, Dan; Bruschweiler-Li, Lei; Zhang, Fengli; Brüschweiler, Rafael (2015-08-18). "Modulation and Functional Role of the Orientations of the N- and P-Domains of Cu+ -Transporting ATPase along the Ion Transport Cycle". Biochemistry. 54 (32): 5095–5102. ISSN 1520-4995. PMID 26196187. doi:10.1021/acs.biochem.5b00420. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Cation transporting ATPase, C-terminus Provide feedback

Members of this families are involved in Na+/K+, H+/K+, Ca++ and Mg++ transport. This family represents 5 transmembrane helices.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006068

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 [PUBMED:15473999, PUBMED:15078220]. 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 [PUBMED:20450191]. They are also found in bacteria [PUBMED:9741106].
  • 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 [PUBMED:18937357, PUBMED:1385979].
  • 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.

P-ATPases (also known as E1-E2 ATPases) (EC) are found in bacteria and in a number of eukaryotic plasma membranes and organelles [PUBMED:9419228]. 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+, Mg2+, Ca2+, Ag+ and Ag2+, Zn2+, Co2+, Pb2+, Ni2+, Cd2+, Cu+ and Cu2+. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

This entry represents the conserved C-terminal region found in several classes of cation-transporting P-type ATPases, including those that transport H+ (EC), Na+ (EC), Ca2+ (EC), Na+/K+ (EC), and H+/K+ (EC). In the H+/K+- and Na+/K+-exchange P-ATPases, this domain is found in the catalytic alpha chain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_137 (release 2.1)
Previous IDs: Na_K_ATPase_C;
Type: Family
Author: Bateman A, Griffiths-Jones SR
Number in seed: 135
Number in full: 13024
Average length of the domain: 180.10 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 18.85 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.1 27.1
Trusted cut-off 27.1 27.1
Noise cut-off 27.0 27.0
Model length: 182
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


There are 9 interactions for this family. More...

ATP1G1_PLM_MAT8 E1-E2_ATPase Na_K-ATPase Sarcolipin Na_K-ATPase Hydrolase E1-E2_ATPase Cation_ATPase_N Cation_ATPase_C


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Cation_ATPase_C domain has been found. There are 128 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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