RegulonDB RegulonDB 11.1: Gene Form
   

nhaA gene in Escherichia coli K-12 genome


Gene local context to scale (view description)

nhaA nhaR sokC mokC NhaR NhaR NhaR NhaR TSS_43 TSS_43 TSS_42 TSS_42 nhaAp1 nhaAp1 nhaAp2 nhaAp2 TSS_41 TSS_41 sokCp sokCp

Gene      
Name: nhaA    Texpresso search in the literature
Synonym(s): ECK0020, EG10652, ant, antA, b0019
Genome position(nucleotides): 17489 --> 18655
Strand: forward
Sequence: Get nucleotide sequence FastaFormat
GC content %:  
 51.41
External database links:  
ASAP:
 ABE-0000068
CGSC:
 15893
ECHOBASE:
 EB0646
ECOLIHUB:
 nhaA
OU-MICROARRAY:
 b0019
STRING:
 511145.b0019
COLOMBOS: nhaA


Product      
Name: Na+:H+ antiporter NhaA
Synonym(s): Ant, AntA, NhaA
Sequence: Get amino acid sequence Fasta Format
Cellular location: inner membrane
Molecular weight: 41.356
Isoelectric point: 9.545
Motif(s):
 
Type Positions Sequence Comment
6 -> 380 RFFSSDASGGIILIIAAILAMIMANSGATSGWYHDFLETPVQLRVGSLEINKNMLLWINDALMAVFFLLVGLEVKRELMQGSLASLRQAAFPVIAAIGGMIVPALLYLAFNYADPITREGWAIPAATDIAFALGVLALLGSRVPLALKIFLMALAIIDDLGAIIIIALFYTNDLSMASLGVAAVAIAVLAVLNLCGARRTGVYILVGVVLWTAVLKSGVHATLAGVIVGFFIPLKEKHGRSPAKRLEHVLHPWVAYLILPLFAFANAGVSLQGVTLDGLTSILPLGIIAGLLIGKPLGISLFCWLALRLKLAHLPEGTTYQQIMVVGILCGIGFTMSIFIASLAFGSVDPELINWAKLGILVGSISSAVIGYSWL
12 -> 30 ASGGIILIIAAILAMIMAN UniProt: Helical; Name=1.
45 -> 58 PVQLRVGSLEINKN UniProt: Important for dimerization; Sequence Annotation Type: region of interest.
59 -> 85 MLLWINDALMAVFFLLVGLEVKRELMQ UniProt: Helical; Name=2.
65 -> 65 D D → C: increased Km to Na+ and Li+; altered pH dependence of transporter

 
Classification:
Multifun Terms (GenProtEC)  
  4 - transport --> 4.2 - Electrochemical potential driven transporters --> 4.2.A - Porters (Uni-, Sym- and Antiporters)
  5 - cell processes --> 5.5 - adaptations --> 5.5.4 - pH
  6 - cell structure --> 6.1 - membrane
Gene Ontology Terms (GO)  
cellular_component GO:0016020 - membrane
GO:0005886 - plasma membrane
GO:0005887 - integral component of plasma membrane
GO:0016021 - integral component of membrane
molecular_function GO:1901612 - cardiolipin binding
GO:0015297 - antiporter activity
GO:0015081 - sodium ion transmembrane transporter activity
GO:0015385 - sodium:proton antiporter activity
biological_process GO:0010446 - response to alkaline pH
GO:0006811 - ion transport
GO:0006885 - regulation of pH
GO:0051453 - regulation of intracellular pH
GO:0006814 - sodium ion transport
GO:0009651 - response to salt stress
GO:0055085 - transmembrane transport
GO:0035725 - sodium ion transmembrane transport
Note(s): Note(s): ...[more].
Reference(s): [1] Alhadeff R., et al., 2015
[2] Carmel O., et al., 1997
[3] Cymer F., et al., 2013
[4] Dibrov P., et al., 2005
[5] Dzafic E., et al., 2009
[6] Hilger D., et al., 2005
[7] Huang Y., et al., 2016
[8] Inoue H., et al., 1998
[9] Inoue H., et al., 2001
[10] Kedrov A., et al., 2008
[11] Kedrov A., et al., 2006
[12] Kedrov A., et al., 2005
[13] Kedrov A., et al., 2004
[14] Kedrov A., et al., 2006
[15] Mager T., et al., 2011
[16] Masrati G., et al., 2018
[17] Masrati G., et al., 2020
[18] Mondal R., et al., 2021
[19] Olkhova E., et al., 2006
[20] Olkhova E., et al., 2009
[21] Padan E. 2011
[22] Padan E., et al., 2015
[23] Padan E., et al., 2015
[24] Padan E., et al., 2004
[25] Padan E., et al., 1998
[26] Pinner E., et al., 1995
[27] Pinner E., et al., 1994
[28] Ravna AW., et al., 2001
[29] Rimon A., et al., 2012
[30] Rowbury RJ., et al., 1994
[31] Rowbury RJ., et al., 1996
[32] Schushan M., et al., 2012
[33] Screpanti E., et al., 2006
[34] Shijuku T., et al., 2001
[35] Trchounian A., et al., 1999
[36] Tzubery T., et al., 2008
[37] Venturi M., et al., 2000
[38] Wu X., et al., 2013
[39] Zuber D., et al., 2005
External database links:  
ALPHAFOLD:
 P13738
DIP:
 DIP-10335N
ECOCYC:
 NHAA-MONOMER
ECOLIWIKI:
 b0019
INTERPRO:
 IPR023171
INTERPRO:
 IPR004670
PANTHER:
 PTHR30341
PDB:
 4AU5
PDB:
 4ATV
PDB:
 1ZCD
PDB:
 3FI1
PFAM:
 PF06965
PRIDE:
 P13738
PRODB:
 PRO_000023379
REFSEQ:
 NP_414560
SMR:
 P13738
UNIPROT:
 P13738


Operon      
Name: nhaAR         
Operon arrangement:
Transcription unit        Promoter
nhaAR
nhaAR
nhaR


Transcriptional Regulation      
Display Regulation             
Activated by: NhaR
Repressed by: H-NS


Elements in the selected gene context region unrelated to any object in RegulonDB      

  Type Name Post Left Post Right Strand Notes Evidence (Confirmed, Strong, Weak) References
  promoter TSS_41 16961 reverse nd [RS-EPT-CBR] [40]
  promoter TSS_42 18023 forward nd [RS-EPT-CBR] [40]
  promoter TSS_43 18025 forward nd [RS-EPT-CBR] [40]


Evidence    

 [RS-EPT-CBR] RNA-seq using two enrichment strategies for primary transcripts and consistent biological replicates


Reference(s)    

 [1] Alhadeff R., Warshel A., 2015, Simulating the function of sodium/proton antiporters., Proc Natl Acad Sci U S A 112(40):12378-83

 [2] 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

 [3] Cymer F., von Heijne G., 2013, Cotranslational folding of membrane proteins probed by arrest-peptide-mediated force measurements., Proc Natl Acad Sci U S A 110(36):14640-5

 [4] Dibrov P., Rimon A., Dzioba J., Winogrodzki A., Shalitin Y., Padan E., 2005, 2-Aminoperimidine, a specific inhibitor of bacterial NhaA Na(+)/H(+) antiporters., FEBS Lett 579(2):373-8

 [5] Dzafic E., Klein O., Screpanti E., Hunte C., Mantele W., 2009, Flexibility and dynamics of NhaA Na+/H+-antiporter of Escherichia coli studied by Fourier transform infrared spectroscopy., Spectrochim Acta A Mol Biomol Spectrosc 72(1):102-9

 [6] 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

 [7] Huang Y., Chen W., Dotson DL., Beckstein O., Shen J., 2016, Mechanism of pH-dependent activation of the sodium-proton antiporter NhaA., Nat Commun 7:12940

 [8] 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

 [9] 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

 [10] Kedrov A., Appel M., Baumann H., Ziegler C., Muller DJ., 2008, Examining the dynamic energy landscape of an antiporter upon inhibitor binding., J Mol Biol 375(5):1258-66

 [11] 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

 [12] Kedrov A., Krieg M., Ziegler C., Kuhlbrandt W., Muller DJ., 2005, Locating ligand binding and activation of a single antiporter., EMBO Rep 6(7):668-74

 [13] 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

 [14] Kedrov A., Ziegler C., Muller DJ., 2006, Differentiating ligand and inhibitor interactions of a single antiporter., J Mol Biol 362(5):925-32

 [15] Mager T., Rimon A., Padan E., Fendler K., 2011, Transport mechanism and pH regulation of the Na+/H+ antiporter NhaA from Escherichia coli: an electrophysiological study., J Biol Chem 286(26):23570-81

 [16] Masrati G., Dwivedi M., Rimon A., Gluck-Margolin Y., Kessel A., Ashkenazy H., Mayrose I., Padan E., Ben-Tal N., 2018, Broad phylogenetic analysis of cation/proton antiporters reveals transport determinants., Nat Commun 9(1):4205

 [17] Masrati G., Mondal R., Rimon A., Kessel A., Padan E., Lindahl E., Ben-Tal N., 2020, An angular motion of a conserved four-helix bundle facilitates alternating access transport in the TtNapA and EcNhaA transporters., Proc Natl Acad Sci U S A 117(50):31850-31860

 [18] Mondal R., Rimon A., Masrati G., Ben-Tal N., Friedler A., Padan E., 2021, Towards Molecular Understanding of the pH Dependence Characterizing NhaA of Which Structural Fold is Shared by Other Transporters., J Mol Biol 433(19):167156

 [19] 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

 [20] Olkhova E., Kozachkov L., Padan E., Michel H., 2009, Combined computational and biochemical study reveals the importance of electrostatic interactions between the "pH sensor" and the cation binding site of the sodium/proton antiporter NhaA of Escherichia coli., Proteins 76(3):548-59

 [21] Padan E., 2011, Regulation of NhaA by protons., Compr Physiol 1(4):1711-9

 [22] Padan E., Danieli T., Keren Y., Alkoby D., Masrati G., Haliloglu T., Ben-Tal N., Rimon A., 2015, NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability., Proc Natl Acad Sci U S A 112(41):E5575-82

 [23] Padan E., Dwivedi M., 2015, Overexpression, Isolation, Purification, and Crystallization of NhaA., Methods Enzymol 557:135-48

 [24] 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

 [25] 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

 [26] 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

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

 [28] Ravna AW., Sylte I., Dahl SG., 2001, Molecular model of the Escherichia coli Na1/H1 antiporter NhaA., Receptors Channels 7(4):319-28

 [29] Rimon A., Kozachkov-Magrisso L., Padan E., 2012, The unwound portion dividing helix IV of NhaA undergoes a conformational change at physiological pH and lines the cation passage., Biochemistry 51(47):9560-9

 [30] Rowbury RJ., Goodson M., Humphrey TJ., 1994, Sodium chloride induces an NhaA/NhaR-independent acid sensitivity at neutral external pH in Escherichia coli., Appl Environ Microbiol 60(5):1630-4

 [31] Rowbury RJ., Hussain NH., 1996, Exposure of Escherichia coli to acid habituation conditions sensitizes it to alkaline stress., Lett Appl Microbiol 22(1):57-61

 [32] Schushan M., Rimon A., Haliloglu T., Forrest LR., Padan E., Ben-Tal N., 2012, A model-structure of a periplasm-facing state of the NhaA antiporter suggests the molecular underpinnings of pH-induced conformational changes., J Biol Chem 287(22):18249-61

 [33] Screpanti E., Padan E., Rimon A., Michel H., Hunte C., 2006, Crucial steps in the structure determination of the Na+/H+ antiporter NhaA in its native conformation., J Mol Biol 362(2):192-202

 [34] Shijuku T., Saito H., Kakegawa T., Kobayashi H., 2001, Expression of sodium/proton antiporter NhaA at various pH values in Escherichia coli., Biochim Biophys Acta 1506(3):212-7

 [35] Trchounian A., Kobayashi H., 1999, Fermenting Escherichia coli is able to grow in media of high osmolarity, but is sensitive to the presence of sodium ion., Curr Microbiol 39(2):109-14

 [36] Tzubery T., Rimon A., Padan E., 2008, Structure-based Functional Study Reveals Multiple Roles of Transmembrane Segment IX and Loop VIII-IX in NhaA Na+/H+ Antiporter of Escherichia coli at Physiological pH., J Biol Chem 283(23):15975-87

 [37] Venturi M., Rimon A., Gerchman Y., Hunte C., Padan E., Michel H., 2000, The monoclonal antibody 1F6 identifies a pH-dependent conformational change in the hydrophilic NH(2) terminus of NhaA Na(+)/H(+) antiporter of Escherichia coli., J Biol Chem 275(7):4734-42

 [38] Wu X., Altman R., Eiteman MA., Altman E., 2013, Effect of overexpressing nhaA and nhaR on sodium tolerance and lactate production in Escherichia coli., J Biol Eng 7(1):3

 [39] Zuber D., Krause R., Venturi M., Padan E., Bamberg E., Fendler K., 2005, Kinetics of charge translocation in the passive downhill uptake mode of the Na+/H+ antiporter NhaA of Escherichia coli., Biochim Biophys Acta 1709(3):240-50

 [40] Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muñiz-Rascado L, García-Sotelo JS, Weiss V, Solano-Lira H, Martínez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernández S, Alquicira-Hernández K, López-Fuentes A, Porrón-Sotelo L, Huerta AM, Bonavides-Martínez C, Balderas-Martínez YI, Pannier L, Olvera M, Labastida A, Jiménez-Jacinto V, Vega-Alvarado L, Del Moral-Chávez V, Hernández-Alvarez A, Morett E, Collado-Vides J., 2012, RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more., Nucleic Acids Res.

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