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Escherichia coli K-12 substr. MG1655 Transporter: sodium:H+ antiporter NhaA



Gene: nhaA Accession Numbers: EG10652 (EcoCyc), b0019, ECK0020

Synonyms: ant, antA, hyc

Regulation Summary Diagram: ?

Subunit composition of sodium:H+ antiporter NhaA = [NhaA]2

Summary:
NhaA is a sodium ion/proton antiporter that uses the proton electrochemical gradient to expel sodium ions from the cytoplasm and functions primarily in the adaptation to high salinity at alkaline pH. NhaA is also believed to be responsible for adaptation to alkaline pH when sodium is available. NhaA is one of the three known sodium ion/proton antiporters in E. coli along with NhaB and ChaA, though there are other mechanisms for Na+ extrusion such as NDH-I complicating the determination of the precise roles of each of the transporters.

Electron cryo-microscopic analysis and antibody tests have suggested a 12 transmembrane helical structure of NhaA, with both N and C termini located in the cytoplasm [Rothman96, Williams00]. A projection map at 4.0 Å resolution, and 3-D maps at 7.0 Å, and 14.0 Å resolutions have been generated by electron cryomicroscopy of two-dimensional crystals [Williams99, Williams00]. The structure of NhaA has been determined by X-ray crystallography to a resolution of 3.45 Å [Hunte05], though in this structure one of the monomers has been flipped relative to the native form such that it is in a non-physiological, upside-down conformation [Rimon07]. Crosslinking and co-purification studies of NhaA and NhaA mutants show that NhaA is a dimer within the membrane [Rimon07]. However, monomers are the functional unit, and dimers are only important under conditions of extreme stress, possibly due to increased stability [Rimon07, Herz09]. Molecular dynamics simulations revealed the residues required for ion exchange. Na+ binds D164 when it is deprotonated. Upon protonation of D164 Na+ is released. If D163 is protonated a conformational change occurs, and Na+ is released into the periplasm. If D163 is not protonated Na+ is released back into the cytoplasm [Arkin07]. The flexibility and dynamics of the Na+/H+-antiporter have been studied using Fourier transform infrared spectroscopy [Džafi08].

NhaA has been purified and reconstituted into sodium-loaded proteoliposomes and demonstrated to transport sodium ions and protons with a 1:2 stoichiometry [Taglicht93, Taglicht91] independent of pH between 7.2 and 8.1 [Taglicht93]. NhaA is also capable of transporting Li+ and is involved in lithium detoxification [Inaba94]. One of the most striking features of NhaA is its extreme sensitivity to pH, though this has been suggested in expression studies with LacZ fusions to be a result of low active ChaA being unable to maintain low intracellular Na+ concentrations under alkaline conditions [Shijuku01]. The activity of NhaA increases 2000-fold between pH 6.5 and 8.5 concurrent with a conformational change [Rothman97, Olkhova07]. Insertion mutation experiments have suggested the involvement of loop VIII-IX in this pH-induced conformational change [Gerchman99]. Other studies have confirmed the involvement of this region in the pH sensing mechanism, the translocation of the transmembrane regions XI and IV and in the determination of the Na+/H+ stoichiometry [Tzubery08]. Cryo electron microscopy of two dimensional crystals has identified a two step conformational change in NhaA in response to pH or substrate ions [Appel09].

NhaA effects Na+/Na+ and Na+/Li+ exchange with a Km for Na+ influx of 1.1 mM during Na+/Na+ exchange [Dibrov93]. NhaA also effects Ca2+/H+ exchange with a Km of 2 mM as well as Na+/Ca+ exchange [Dibrov93a].

Mutants lacking Na+ extrusion are capable of growth at alkaline pH only in media containing low Na+ concentrations [Ohyama92]. nhaB mutants are nearly Na+/H+ antiporter negative up to pH 8.0 where NhaA and ChaA become active [Thelen91], though NhaA is able to provide sufficient activity across the spectrum of pH and Na+ concentrations in the nhaB mutant for normal viability [Pinner93, Shijuku01]. A nhaB knockout mutant was unable to grow in a high pH medium (above 8.0), and the intracellular pH was not maintained at 7.6 as in wild-type [Shimamoto94]. Complementation of the nhaB mutant with the cloned nhaA gene increased sodium ion/proton antiporter activity, but did not restore the defects in growth and intracellular pH [Shimamoto94]. A mutant lacking NhaA and ChaA but with a functional NhaB excreted Na+ at pH less than 8 [Ohyama94, Sakuma98a]. NhaB is unable to extrude sufficient Na+ at pH 8.5 to allow growth of a nhaA chaA mutant (RS1, TO112) in media with elevated sodium concentrations [Ohyama92, Ohyama94]. RS1 is capable of normal growth, even at pH 8.5, when the Na+ concentration is sufficiently low [Ohyama92]. These results suggest NhaA and ChaA transporters have no role in pH regulation, and NhaB has no role in adapting to high salinity at alkaline pH [Ohyama92]. The Na+ sensitivity of nhaA nhaB mutants is abolished by second site suppressor mutations [HarelBronstein95], by increasing the K+ concentration in the medium or adding mannitol, which increases medium osmolarity and allows Na+ transport by some other mechanism [HarelBronstein95, Verkhovskaya98], and upon growth in glycerol/fumarate minimal medium due to the Na+-transporting capability of NADH dehydrogenase I (NDH-I) [Steuber00]. Respiration-dependent efflux of Na+ occurs in the absence of NhaA and NhaB possibly due to a Na+, K+/H+ pump that requires both Na+ and K+ to function [Verkhovskaya96].

Expression of nhaA, as measured using LacZ fusions, is induced by Na+ or Li+ in the medium [Karpel91]. Northern hybridization and analysis of nhaA-lacZ gene fusion has demonstrated that nhaA transcription is dependent on NhaR, a positive regulator of the LysR family, and sodium ion, an environmental signal for nhaA transcription. Transcription of the two nhaA promoters has been studied [Dover01]. Deletion of nhaR results in increased sensitivity to Na+ and Li+ at alkaline pH which can be complemented by supplying nhaA on a multicopy plasmid [RahavManor92]. H-NS also plays a role in regulation of nhaA expression [Dover96, Dover01].

Reviews: [Padan93, Padan94, Serrano96, Rowbury97, Padan99, Padan01, Wiebe01, Venturi03, Padan04, Kedrov06, Padan09]

Citations: [Gerchman93, Carmel94, Rowbury94, Pinner94, Inoue95, Pinner95, Rimon95, Rowbury96, Olami97, Noumi97, Carmel97, Rimon98, Inoue98, Padan98, Trchounian99, Venturi00, Ravna01, Gerchman01, Inoue01, Galili02, Rimon02, Tzubery04, Galili04, Kedrov04, Hilger05, Kedrov06a, Olkhova06, Screpanti06, Kedrov06b, Kozachkov07, Goldberg87]

Gene Citations: [Pannuri12]

Locations: inner membrane

Map Position: [17,489 -> 18,655] (0.38 centisomes)
Length: 1167 bp / 388 aa

Molecular Weight of Polypeptide: 41.356 kD (from nucleotide sequence), 35.0 kD (experimental) [Karpel88 ]

Unification Links: ASAP:ABE-0000068 , CGSC:15893 , DIP:DIP-10335N , EchoBASE:EB0646 , EcoGene:EG10652 , EcoliWiki:b0019 , OU-Microarray:b0019 , PortEco:nhaA , PR:PRO_000023379 , Protein Model Portal:P13738 , RefSeq:NP_414560 , RegulonDB:EG10652 , SMR:P13738 , String:511145.b0019 , UniProt:P13738

Relationship Links: InterPro:IN-FAMILY:IPR004670 , InterPro:IN-FAMILY:IPR023171 , PDB:Structure:1zcd , PDB:Structure:1ZCD , PDB:Structure:3FI1 , PDB:Structure:4ATV , PDB:Structure:4AU5 , Pfam:IN-FAMILY:PF06965

In Paralogous Gene Group: 401 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006814 - sodium ion transport Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Taglicht91]
GO:0006883 - cellular sodium ion homeostasis Inferred from experiment [Ohyama92]
GO:0015992 - proton transport Inferred from experiment [Taglicht91]
GO:0098655 - cation transmembrane transport Inferred from experiment [Taglicht91]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a]
GO:0006811 - ion transport Inferred by computational analysis [UniProtGOA11a]
GO:0006885 - regulation of pH Inferred by computational analysis [GOA01a]
GO:0035725 - sodium ion transmembrane transport Inferred by computational analysis [GOA06]
GO:0055085 - transmembrane transport Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0015491 - cation:cation antiporter activity Inferred from experiment [Taglicht91]
GO:0015081 - sodium ion transmembrane transporter activity Inferred by computational analysis [GOA06]
GO:0015297 - antiporter activity Inferred by computational analysis [UniProtGOA11a, GOA06]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06, DiazMejia09, Daley05]
GO:0016020 - membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Taglicht93]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]

MultiFun Terms: cell processes adaptations pH
cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Essentiality data for nhaA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Created 12-Oct-2007 by Johnson A , JCVI


Enzymatic reaction of: sodium:H+ antiporter NhaA


Sequence Features

Feature Class Location Common Name Citations Comment
Transmembrane-Region 12 -> 30 TMS I
[Hunte05]
 
Protein-Segment 45 -> 58  
[UniProt10a]
UniProt: Important for dimerization; Sequence Annotation Type: region of interest;
Transmembrane-Region 59 -> 85 TMS II
[Hunte05]
 
Transmembrane-Region 95 -> 116 TMS III
[Hunte05]
 
Transmembrane-Region 121 -> 143  
[UniProt10]
UniProt: Helical; Name=4;
Transmembrane-Region 121 -> 131 TMS IVp
[Hunte05]
 
Mutagenesis-Variant 133  
[Inoue95, Gerchman93, UniProt11]
Alternate sequence: D → N; UniProt: Loss of antiport activity. Abolishes ability to grow on high salt medium.
Amino-Acid-Site 133  
[UniProt10]
UniProt: Essential for antiport activity; Sequence Annotation Type: site;
Transmembrane-Region 134 -> 143 TMS IVc
[Hunte05]
 
Transmembrane-Region 150 -> 175 TMS V
[Hunte05]
 
Mutagenesis-Variant 163  
[Gerchman01, Inoue95, Gerchman93, UniProt11]
Alternate sequence: D → N; UniProt: Loss of antiport activity. Abolishes ability to grow on high salt medium.
Alternate sequence: D → C; UniProt: Loss of antiport activity.
Amino-Acid-Site 163  
[UniProt10]
UniProt: Essential for antiport activity; Sequence Annotation Type: site;
Amino-Acid-Site 164, 163  
[UniProt10]
UniProt: Essential for antiport activity; Sequence Annotation Type: site;
Mutagenesis-Variant 164  
[Inoue95, Gerchman93, UniProt11]
Alternate sequence: D → N; UniProt: Loss of antiport activity. Abolishes ability to grow on high salt medium.
Transmembrane-Region 182 -> 200 TMS VI
[Hunte05]
 
Transmembrane-Region 205 -> 218 TMS VII
[Hunte05]
 
Transmembrane-Region 223 -> 236 TMS VIII
[Hunte05]
 
Mutagenesis-Variant 225  
[Gerchman01, Rimon95, Gerchman93, UniProt11]
Alternate sequence: H → R; UniProt: Shifts threshold for pH-sensitive inactivation.
Alternate sequence: H → D; UniProt: Shifts threshold for pH-sensitive inactivation.
Alternate sequence: H → S; UniProt: Slightly reduced antiport activity. No effect on pH sensitivity.
Alternate sequence: H → C; UniProt: Slightly reduced antiport activity. No effect on pH sensitivity.
Alternate sequence: H → A; UniProt: Loss of antiport activity. Abolishes ability to grow at alkaline pH.
Amino-Acid-Site 241  
[UniProt10a]
UniProt: Important for pH sensor; Sequence Annotation Type: site; Non-Experimental Qualifier: probable;
Transmembrane-Region 247 -> 271 TMS IX
[Hunte05]
 
Amino-Acid-Site 249  
[UniProt10a]
UniProt: Important for pH sensor; Sequence Annotation Type: site; Non-Experimental Qualifier: probable;
Amino-Acid-Site 252  
[UniProt10a]
UniProt: Important for pH sensor; Sequence Annotation Type: site; Non-Experimental Qualifier: probable;
Transmembrane-Region 290 -> 311 TMS X
[Hunte05]
 
Transmembrane-Region 327 -> 350  
[UniProt10]
UniProt: Helical; Name=11;
Transmembrane-Region 327 -> 336 TMS XIc
[Hunte05]
 
Mutagenesis-Variant 338  
[Gerchman01, Gerchman93, UniProt11]
Alternate sequence: G → S; UniProt: Loss of pH-sensitivity.
Transmembrane-Region 340 -> 350 TMS XIp
[Hunte05]
 
Transmembrane-Region 357 -> 382 TMS XII
[Hunte05]
 


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b0019 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10652; confirmed by SwissProt match.


References

Appel09: Appel M, Hizlan D, Vinothkumar KR, Ziegler C, Kuhlbrandt W (2009). "Conformations of NhaA, the Na+/H+ exchanger from Escherichia coli, in the pH-activated and ion-translocating states." J Mol Biol 388(3);659-72. PMID: 19396973

Arkin07: Arkin IT, Xu H, Jensen MO, Arbely E, Bennett ER, Bowers KJ, Chow E, Dror RO, Eastwood MP, Flitman-Tene R, Gregersen BA, Klepeis JL, Kolossvary I, Shan Y, Shaw DE (2007). "Mechanism of Na+/H+ antiporting." Science 317(5839);799-803. PMID: 17690293

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Carmel94: Carmel O, Dover N, Rahav-Manor O, Dibrov P, Kirsch D, Karpel R, Schuldiner S, Padan E (1994). "A single amino acid substitution (Glu134-->Ala) in NhaR1 increases the inducibility by Na+ of the product of nhaA, a Na+/H+ antiporter gene in Escherichia coli." EMBO J 1994;13(8);1981-9. PMID: 8168494

Carmel97: Carmel O, Rahav-Manor O, Dover N, Shaanan B, Padan E (1997). "The Na+-specific interaction between the LysR-type regulator, NhaR, and the nhaA gene encoding the Na+/H+ antiporter of Escherichia coli." EMBO J 16(19);5922-9. PMID: 9312050

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dibrov93: Dibrov PA, Taglicht D (1993). "Mechanism of Na+/H+ exchange by Escherichia coli NhaA in reconstituted proteoliposomes." FEBS Lett 336(3);525-9. PMID: 8282121

Dibrov93a: Dibrov PA (1993). "Calcium transport mediated by NhaA, a Na+/H+ antiporter from Escherichia coli." FEBS Lett 336(3);530-4. PMID: 8282122

Dover01: Dover N, Padan E (2001). "Transcription of nhaA, the main Na(+)/H(+) antiporter of Escherichia coli, is regulated by Na(+) and growth phase." J Bacteriol 183(2);644-53. PMID: 11133959

Dover96: Dover N, Higgins CF, Carmel O, Rimon A, Pinner E, Padan E (1996). "Na+-induced transcription of nhaA, which encodes an Na+/H+ antiporter in Escherichia coli, is positively regulated by nhaR and affected by hns." J Bacteriol 178(22);6508-17. PMID: 8932307

Džafi08: Džafić E, Klein O, Screpanti E, Hunte C, Mantele W (2008). "Flexibility and dynamics of NhaA Na(+)/H(+)-antiporter of Escherichia coli studied by Fourier transform infrared spectroscopy." Spectrochim Acta A Mol Biomol Spectrosc. PMID: 18930435

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Galili02: Galili L, Rothman A, Kozachkov L, Rimon A, Padan E (2002). "Trans membrane domain IV is involved in ion transport activity and pH regulation of the NhaA-Na(+)/H(+) antiporter of Escherichia coli." Biochemistry 41(2);609-17. PMID: 11781101

Galili04: Galili L, Herz K, Dym O, Padan E (2004). "Unraveling functional and structural interactions between transmembrane domains IV and XI of NhaA Na+/H+ antiporter of Escherichia coli." J Biol Chem 279(22);23104-13. PMID: 15039449

Gerchman01: Gerchman Y, Rimon A, Venturi M, Padan E (2001). "Oligomerization of NhaA, the Na+/H+ antiporter of Escherichia coli in the membrane and its functional and structural consequences." Biochemistry 40(11);3403-12. PMID: 11258962

Gerchman93: Gerchman Y, Olami Y, Rimon A, Taglicht D, Schuldiner S, Padan E (1993). "Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli." Proc Natl Acad Sci U S A 90(4);1212-6. PMID: 8381959

Gerchman99: Gerchman Y, Rimon A, Padan E (1999). "A pH-dependent conformational change of NhaA Na(+)/H(+) antiporter of Escherichia coli involves loop VIII-IX, plays a role in the pH response of the protein, and is maintained by the pure protein in dodecyl maltoside." J Biol Chem 1999;274(35);24617-24. PMID: 10455127

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Goldberg87: Goldberg EB, Arbel T, Chen J, Karpel R, Mackie GA, Schuldiner S, Padan E (1987). "Characterization of a Na+/H+ antiporter gene of Escherichia coli." Proc Natl Acad Sci U S A 84(9);2615-9. PMID: 3033655

HarelBronstein95: Harel-Bronstein M, Dibrov P, Olami Y, Pinner E, Schuldiner S, Padan E (1995). "MH1, a second-site revertant of an Escherichia coli mutant lacking Na+/H+ antiporters (delta nhaA delta nhaB), regains Na+ resistance and a capacity to excrete Na+ in a delta microH(+)-independent fashion." J Biol Chem 270(8);3816-22. PMID: 7876124

Herz09: Herz K, Rimon A, Jeschke G, Padan E (2009). "Beta-sheet-dependent dimerization is essential for the stability of NhaA Na+/H+ antiporter." J Biol Chem 284(10);6337-47. PMID: 19129192

Hilger05: Hilger D, Jung H, Padan E, Wegener C, Vogel KP, Steinhoff HJ, Jeschke G (2005). "Assessing oligomerization of membrane proteins by four-pulse DEER: pH-dependent dimerization of NhaA Na+/H+ antiporter of E. coli." Biophys J 89(2);1328-38. PMID: 15894644

Hunte05: Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H (2005). "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH." Nature 435(7046);1197-202. PMID: 15988517

Inaba94: Inaba K, Kuroda T, Shimamoto T, Kayahara T, Tsuda M, Tsuchiya T (1994). "Lithium toxicity and Na+(Li+)/H+ antiporter in Escherichia coli." Biol Pharm Bull 17(3);395-8. PMID: 8019504

Inoue01: Inoue H, Tsuboi Y, Kanazawa H (2001). "Chimeric Na(+)/H(+) antiporters constructed from NhaA of Helicobacter pylori and Escherichia coli: implications for domains of NhaA for pH sensing." J Biochem (Tokyo) 129(4);569-76. PMID: 11275556

Inoue95: Inoue H, Noumi T, Tsuchiya T, Kanazawa H (1995). "Essential aspartic acid residues, Asp-133, Asp-163 and Asp-164, in the transmembrane helices of a Na+/H+ antiporter (NhaA) from Escherichia coli." FEBS Lett 363(3);264-8. PMID: 7737413

Inoue98: Inoue H, Noumi T, Shimomura T, Takimoto N, Tsuchiya T, Kanazawa H (1998). "pH-dependent growth retardation of Escherichia coli caused by overproduction of Na+/H+ antiporter." Biol Pharm Bull 21(11);1128-33. PMID: 9853399

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Karpel88: Karpel R, Olami Y, Taglicht D, Schuldiner S, Padan E (1988). "Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli." J Biol Chem 263(21);10408-14. PMID: 2839489

Karpel91: Karpel R, Alon T, Glaser G, Schuldiner S, Padan E (1991). "Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions." J Biol Chem 1991;266(32);21753-9. PMID: 1657980

Kedrov04: Kedrov A, Ziegler C, Janovjak H, Kuhlbrandt W, Muller DJ (2004). "Controlled unfolding and refolding of a single sodium-proton antiporter using atomic force microscopy." J Mol Biol 340(5);1143-52. PMID: 15236973

Kedrov06: Kedrov A, Muller DJ (2006). "Characterizing folding, structure, molecular interactions and ligand gated activation of single sodium/proton antiporters." Naunyn Schmiedebergs Arch Pharmacol 372(6);400-12. PMID: 16544108

Kedrov06a: Kedrov A, Janovjak H, Ziegler C, Kuhlbrandt W, Muller DJ (2006). "Observing folding pathways and kinetics of a single sodium-proton antiporter from Escherichia coli." J Mol Biol 355(1);2-8. PMID: 16298390

Kedrov06b: Kedrov A, Ziegler C, Muller DJ (2006). "Differentiating ligand and inhibitor interactions of a single antiporter." J Mol Biol 362(5);925-32. PMID: 16935297

Kozachkov07: Kozachkov L, Herz K, Padan E (2007). "Functional and structural interactions of the transmembrane domain X of NhaA, Na+/H+ antiporter of Escherichia coli, at physiological pH." Biochemistry 46(9);2419-30. PMID: 17284054

Noumi97: Noumi T, Inoue H, Sakurai T, Tsuchiya T, Kanazawa H (1997). "Identification and characterization of functional residues in a Na+/H+ antiporter (NhaA) from Escherichia coli by random mutagenesis." J Biochem (Tokyo) 121(4);661-70. PMID: 9163515

Ohyama92: Ohyama T, Imaizumi R, Igarashi K, Kobayashi H (1992). "Escherichia coli is able to grow with negligible sodium ion extrusion activity at alkaline pH." J Bacteriol 174(23);7743-9. PMID: 1332943

Ohyama94: Ohyama T, Igarashi K, Kobayashi H (1994). "Physiological role of the chaA gene in sodium and calcium circulations at a high pH in Escherichia coli." J Bacteriol 1994;176(14);4311-5. PMID: 8021217

Olami97: Olami Y, Rimon A, Gerchman Y, Rothman A, Padan E (1997). "Histidine 225, a residue of the NhaA-Na+/H+ antiporter of Escherichia coli is exposed and faces the cell exterior." J Biol Chem 272(3);1761-8. PMID: 8999858

Olkhova06: Olkhova E, Hunte C, Screpanti E, Padan E, Michel H (2006). "Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications." Proc Natl Acad Sci U S A 103(8);2629-34. PMID: 16477015

Olkhova07: Olkhova E, Padan E, Michel H (2007). "The influence of protonation states on the dynamics of the NhaA antiporter from Escherichia coli." Biophys J 92(11);3784-91. PMID: 17350999

Padan01: Padan E, Venturi M, Gerchman Y, Dover N (2001). "Na(+)/H(+) antiporters." Biochim Biophys Acta 1505(1);144-57. PMID: 11248196

Padan04: Padan E, Tzubery T, Herz K, Kozachkov L, Rimon A, Galili L (2004). "NhaA of Escherichia coli, as a model of a pH-regulated Na+/H+antiporter." Biochim Biophys Acta 1658(1-2);2-13. PMID: 15282168

Padan09: Padan E, Kozachkov L, Herz K, Rimon A (2009). "NhaA crystal structure: functional-structural insights." J Exp Biol 212(Pt 11);1593-603. PMID: 19448069

Padan93: Padan E, Schuldiner S (1993). "Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in cells." J Bioenerg Biomembr 25(6);647-69. PMID: 8144493

Padan94: Padan E, Schuldiner S (1994). "Molecular physiology of the Na+/H+ antiporter in Escherichia coli." J Exp Biol 196;443-56. PMID: 7823039

Padan98: Padan E, Venturi M, Michel H, Hunte C (1998). "Production and characterization of monoclonal antibodies directed against native epitopes of NhaA, the Na+/H+ antiporter of Escherichia coli." FEBS Lett 441(1);53-8. PMID: 9877164

Padan99: Padan E, Gerchman Y, Rimon A, Rothman A, Dover N, Carmel-Harel O (1999). "The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+." Novartis Found Symp 1999;221;183-96; discussion 196-9. PMID: 10207920

Pannuri12: Pannuri A, Yakhnin H, Vakulskas CA, Edwards AN, Babitzke P, Romeo T (2012). "Translational repression of NhaR, a novel pathway for multi-tier regulation of biofilm circuitry by CsrA." J Bacteriol 194(1);79-89. PMID: 22037401

Pinner93: Pinner E, Kotler Y, Padan E, Schuldiner S (1993). "Physiological role of nhaB, a specific Na+/H+ antiporter in Escherichia coli." J Biol Chem 1993;268(3);1729-34. PMID: 8093613

Pinner94: Pinner E, Padan E, Schuldiner S (1994). "Kinetic properties of NhaB, a Na+/H+ antiporter from Escherichia coli." J Biol Chem 1994;269(42);26274-9. PMID: 7929345

Pinner95: Pinner E, Padan E, Schuldiner S (1995). "Amiloride and harmaline are potent inhibitors of NhaB, a Na+/H+ antiporter from Escherichia coli." FEBS Lett 365(1);18-22. PMID: 7774707

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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