Cation_ATPase_N

Cation transporter/ATPase, N-terminus

• SMART accession number: SM00831
• Description: This entry represents the conserved N-terminal region found in several classes of cation-transporting P-type ATPases, including those that transport H+, Na+, Ca2+, Na+/K+, and H+/K+. In the H+/K+- and Na+/K+-exchange P-ATPases, this domain is found in the catalytic alpha chain. In gastric H+/K+-ATPases, this domain undergoes reversible sequential phosphorylation inducing conformational changes that may be important for regulating the function of these ATPases (PUBMED:12480547), (PUBMED:12529322).
• Interpro abstract (IPR004014):

  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 [ (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 ⁺ 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 [ (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.

  This entry represents the conserved N-terminal region found in several classes of cation-transporting P-type ATPases, including those that transport H ⁺ ( EC 3.6.3.6 ), Na ⁺ ( EC 3.6.3.7 ), Ca ²⁺ ( EC 3.6.3.8 ), Na ⁺ /K ⁺ ( EC 3.6.3.9 ), and H ⁺ /K ⁺ ( EC 3.6.3.10 ). In the H ⁺ /K ⁺ - and Na ⁺ /K ⁺ -exchange P-ATPases, this domain is found in the catalytic alpha chain. In gastric H ⁺ /K ⁺ -ATPases, this domain undergoes reversible sequential phosphorylation inducing conformational changes that may be important for regulating the function of these ATPases [ (PUBMED:12480547) (PUBMED:12529322) ].

There are 45454 Cation_ATPase_N domains in 45418 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: transport
Binding / catalysis: membrane-bound

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Fujitani N et al.
• Structure determination and conformational change induced by tyrosinephosphorylation of the N-terminal domain of the alpha-chain of pig gastricH+/K+-ATPase.
• Biochem Biophys Res Commun. 2003; 300: 223-9

It has been well established that phosphorylation is an important reactionfor the regulation of protein functions. In the N-terminal domain of thealpha-chain of pig gastric H(+)/K(+)-ATPase, reversible sequentialphosphorylation occurs at Tyr 10 and Tyr 7. In this study, we determinedthe structure of the peptide involving the residues from Gly 2 to Gly 34of pig gastric H(+)/K(+)-ATPase and investigated the tyrosinephosphorylation-induced conformational change using CD and NMRexperiments. The solution structure showed that the N-terminal fragmenthas a helical conformation, and the peptide adopted two alpha-helices in50% trifluoroethanol (TFE) solvent, suggesting that the peptide has a highhelical propensity under hydrophobic conditions. Furthermore, the CD andNMR data suggested that the structure of the N-terminal fragment becomesmore disordered as a result of phosphorylation of Tyr 10. Thisconformational change induced by the phosphorylation of Tyr 10 might be anadvantageous reaction for sequential phosphorylation and may be importantfor regulating the function of H(+)/K(+)-ATPase.

• Segall L, Javaid ZZ, Carl SL, Lane LK, Blostein R
• Structural basis for alpha1 versus alpha2 isoform-distinct behavior of theNa,K-ATPase.
• J Biol Chem. 2003; 278: 9027-34

We showed earlier that the kinetic behavior of the alpha2 isoform of theNa,K-ATPase differs from the ubiquitous alpha1 isoform primarily by ashift in the steady-state E(1)/E(2) equilibrium of alpha2 in favor of E(1)form(s). The aim of the present study was to identify regions of the alphachain that confer the alpha1/alpha2 distinct behavior using a mutagenesisand chimera approach. Criteria to assess shifts in conformationalequilibrium included (i) K(+) sensitivity of Na-ATPase measured atmicromolar ATP, under which condition E(2)(K(+)) --> E(1) + K(+) becomesrate-limiting, (ii) changes in K'(ATP) for low affinity ATP binding, (iii)vanadate sensitivity of Na,K-ATPase activity, and (iv) the rate of thepartial reaction E(1)P --> E(2)P. We first confirmed that interactionsbetween the cytoplasmic domains of alpha2 that modulate conformationalshifts are fundamentally similar to those of alpha1, suggesting that thepredilection of alpha2 for E(1) state(s) is due to differences in primarystructure of the two isoforms. Kinetic behavior of the alpha1/alpha2chimeras indicates that the difference in E(1)/E(2) poise of the twoisoforms cannot be accounted for by their notably distinct N termini, butrather by the front segment extending from the cytoplasmic N terminus tothe C-terminal end of the extracellular loop between transmembranes 3 and4, with a lesser contribution of the alpha1/alpha2 divergent portionwithin the M4-M5 loop near the ATP binding domain. In addition, we showthat the E(1) shift of alpha2 results primarily from differences in theconformational transition of the dephosphoenzyme, (E(2)(K(+)) --> E(1) +K(+)), rather than phosphoenzyme (E(1)P --> E(2)P).

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
36.34	map00500	Starch and sucrose metabolism
36.34	map00790	Folate biosynthesis
15.99	map00190	Oxidative phosphorylation
11.34	map04020	Calcium signaling pathway

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Cation_ATPase_N domain which could be assigned to a KEGG orthologous group, and not all proteins containing Cation_ATPase_N domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of Cation_ATPase_N domains in PDB

PDB code	Title
1iwo	Crystal structure of the SR Ca2+-ATPase in the absence of Ca2+
1kju	Ca2+-ATPase in the E2 State
1mhs	Model of Neurospora crassa proton ATPase
1su4	Crystal structure of calcium ATPase with two bound calcium ions
1t5s	Structure of the (SR)Ca2+-ATPase Ca2-E1-AMPPCP form
1t5t	Structure of the (SR)Ca2+-ATPase Ca2-E1-ADP:AlF4- form
1vfp	Crystal structure of the SR CA2+-ATPase with bound AMPPCP
1wpg	Crystal structure of the SR CA2+-ATPase with MGF4
1xp5	Structure Of The (Sr)Ca2+-ATPase E2-AlF4- Form
2agv	Crystal structure of the SR CA2+-ATPASE with BHQ and TG
2by4	SR Ca(2+)-ATPase in the HnE2 state complexed with the thapsigargin derivative Boc-12ADT.
2c88	Crystal Structure Of (SR) Calcium-ATPase E2(Tg):AMPPCP form
2c8k	Crystal Structure of (SR) Calcium-ATPase E2(Tg) with partially occupied AMPPCP site
2c8l	Crystal Structure of (SR) Calcium-ATPase E2(Tg) form
2c9m	Structure of (SR) Calcium-ATPase in the Ca2E1 state solved in a P1 crystal form.
2dqs	Crystal structure of the calcium pump with amppcp in the absence of calcium
2ear	P21 crystal of the SR CA2+-ATPase with bound TG
2eat	Crystal structure of the SR CA2+-ATPASE with bound CPA and TG
2eau	Crystal structure of the SR CA2+-ATPASE with bound CPA in the presence of curcumin
2o9j	Crystal structure of calcium atpase with bound magnesium fluoride and cyclopiazonic acid
2oa0	Crystal structure of Calcium ATPase with bound ADP and cyclopiazonic acid
2xzb	Pig Gastric H,K-ATPase with bound BeF and SCH28080
2yfy	SERCA in the HnE2 State Complexed With Debutanoyl Thapsigargin
2yn9	Cryo-EM structure of gastric H+,K+-ATPase with bound rubidium
2zbd	Crystal Structure of the SR Calcium Pump with Bound Aluminium Fluoride, ADP and Calcium
2zbe	Calcium pump crystal structure with bound BeF3 in the absence of calcium and TG
2zbf	Calcium pump crystal structure with bound BeF3 and TG in the absence of calcium
2zbg	Calcium pump crystal structure with bound AlF4 and TG in the absence of calcium
2zxe	Crystal structure of the sodium - potassium pump in the E2.2K+.Pi state
3a3y	Crystal structure of the sodium-potassium pump with bound potassium and ouabain
3ar2	Calcium pump crystal structure with bound AMPPCP and Ca2+
3ar3	Calcium pump crystal structure with bound ADP and TG
3ar4	Calcium pump crystal structure with bound ATP and TG in the absence of Ca2+
3ar5	Calcium pump crystal structure with bound TNP-AMP and TG
3ar6	Calcium pump crystal structure with bound TNP-ADP and TG in the absence of calcium
3ar7	Calcium pump crystal structure with bound TNP-ATP and TG in the absence of Ca2+
3ar8	Calcium pump crystal structure with bound AlF4, TNP-AMP and TG
3ar9	Calcium pump crystal structure with bound BeF3, TNP-AMP and TG in the absence of calcium
3b8e	Crystal structure of the sodium-potassium pump
3b9b	Structure of the E2 beryllium fluoride complex of the SERCA Ca2+-ATPase
3b9r	SERCA Ca2+-ATPase E2 aluminium fluoride complex without thapsigargin
3ba6	Structure of the Ca2E1P phosphoenzyme intermediate of the SERCA Ca2+-ATPase
3fgo	Crystal Structure of the E2 magnesium fluoride complex of the (SR) Ca2+-ATPase with bound CPA and AMPPCP
3fpb	The Structure of Sarcoplasmic Reticulum Ca2+-ATPase Bound To Cyclopiazonic acid with ATP
3fps	The Structure of Sarcoplasmic Reticulum Ca2+-ATPase Bound To Cyclopiazonic and ADP
3ixz	Pig gastric H+/K+-ATPase complexed with aluminium fluoride
3j7t	3J7T
3kdp	Crystal structure of the sodium-potassium pump
3n23	Crystal structure of the high affinity complex between ouabain and the E2P form of the sodium-potassium pump
3n5k	Structure Of The (Sr)Ca2+-ATPase E2-AlF4- Form
3n8g	Structure of the (SR)Ca2+-ATPase Ca2-E1-CaAMPPCP form
3nal	SR Ca(2+)-ATPase in the HnE2 state complexed with the Thapsigargin derivative DTB
3nam	SR Ca(2+)-ATPase in the HnE2 state complexed with the Thapsigargin derivative dOTg
3nan	SR Ca(2+)-ATPase in the HnE2 state complexed with a Thapsigargin derivative Boc-(phi)Tg
3tlm	Crystal Structure of Endoplasmic Reticulum Ca2+-ATPase (SERCA) From Bovine Muscle
3w5a	Crystal structure of the calcium pump and sarcolipin from rabbit fast twitch skeletal muscle in the E1.Mg2+ state
3w5b	Crystal structure of the recombinant SERCA1a (calcium pump of fast twitch skeletal muscle) in the E1.Mg2+ state
3w5c	Crystal structure of the calcium pump in the E2 state free from exogenous inhibitors
3w5d	Crystal structure of the calcium pump in the E2+Pi state
3wgu	Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state without oligomycin
3wgv	Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state with oligomycin
4bew	SERCA bound to phosphate analogue
4h1w	E1 structure of the (SR) Ca2+-ATPase in complex with Sarcolipin
4hqj	Crystal structure of Na+,K+-ATPase in the Na+-bound state
4hyt	Na,K-ATPase in the E2P state with bound ouabain and Mg2+ in the cation-binding site
4j2t	Inhibitor-bound Ca2+ ATPase
4kyt	The structure of superinhibitory phospholamban bound to the calcium pump SERCA1a
4nab	Structure of the (SR)Ca2+-ATPase mutant E309Q in the Ca2-E1-MgAMPPCP form
4res	4RES
4ret	4RET
4uu0	4UU0
4uu1	4UU1
4ux1	4UX1
4ux2	4UX2
4xe5	4XE5
4xou	4XOU
4y3u	4Y3U
4ycl	4YCL
4ycm	4YCM
4ycn	4YCN
5a3q	5A3Q
5a3r	5A3R
5a3s	5A3S
5avq	5AVQ
5avr	5AVR
5avs	5AVS
5avt	5AVT
5avu	5AVU
5avv	5AVV
5avw	5AVW
5avx	5AVX
5avy	5AVY
5avz	5AVZ
5aw0	5AW0
5aw1	5AW1
5aw2	5AW2
5aw3	5AW3
5aw4	5AW4
5aw5	5AW5
5aw6	5AW6
5aw7	5AW7
5aw8	5AW8
5aw9	5AW9
5ksd	5KSD

Links (links to other resources describing this domain)

• INTERPRO: IPR004014
• PFAM: Cation_ATPase_N