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2.A.33.1.1
NhaA Na+:2H+ antiporter (structure determined and mechanism proposed (Williams, 2000; Hunte et al., 2005; Olkhova et al., 2006; Screpanti et al., 2006; Arkin et al., 2007)). The K300R mutant is also electrogenic (C─âlinescu et al. 2017).  TMS II lines the cation passage, and Asp65 is critical for pH activation of the antiporter (Herz et al., 2010). NhaA is subject to pH-activation of the ion-translocating conformation (Appel et al., 2009; Diab et al., 2011). A periplasm-facing state of the NhaA antiporter suggests the molecular underpinnings of the pH-induced conformational changes (Schushan et al., 2012).  A central unwound part of TMS IV appears to line the cation passage channel (Rimon et al. 2012).  TMSs VI and VII are absent from many homologues, are not required for transport or its regulation and function in assembly and stability (Padan et al. 2015). pH-induced conformational changes have been documented (Kozachkov et al. 2007).  Two acidic residues in the binding site that carries the protons in electrogenic CPAs, and a polar residue in the unwound transmembrane helix 4 that determines ion selectivity have been identified. A rationally designed triple mutant successfully converted the electrogenic EcNhaA, to be electroneutral (Masrati et al. 2018).

Accession Number:P13738
Protein Name:NhaA aka ANT aka B0019
Length:388
Molecular Weight:41356.00
Species:Escherichia coli [83333]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate protons, lithium, sodium, Na+

Cross database links:

Genevestigator: P13738
EchoBASE: EB0646
EcoGene: EG10652
eggNOG: COG3004
HEGENOM: HBG665619
DIP: DIP-10335N
RefSeq: AP_000683.1    NP_414560.1   
Entrez Gene ID: 944758   
Pfam: PF06965   
BioCyc: EcoCyc:NHAA-MONOMER    ECOL168927:B0019-MONOMER   
KEGG: ecj:JW0018    eco:b0019   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015491 F:cation:cation antiporter activity
GO:0015081 F:sodium ion transmembrane transporter activity
GO:0006883 P:cellular sodium ion homeostasis
GO:0015992 P:proton transport
GO:0006885 P:regulation of pH
GO:0006814 P:sodium ion transport

References (13)

[1] “Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli.”  Karpel R.et.al.   2839489
[2] “Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region.”  Yura T.et.al.   1630901
[3] “The complete genome sequence of Escherichia coli K-12.”  Blattner F.R.et.al.   9278503
[4] “Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.”  Hayashi K.et.al.   16738553
[5] “Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions.”  Karpel R.et.al.   1657980
[6] “Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli.”  Taglicht D.et.al.   1645730
[7] “Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli.”  Gerchman Y.et.al.   8381959
[8] “Essential aspartic acid residues, Asp-133, Asp-163 and Asp-164, in the transmembrane helices of a Na+/H+ antiporter (NhaA) from Escherichia coli.”  Inoue H.et.al.   7737413
[9] “Replacements of histidine 226 of NhaA-Na+/H+ antiporter of Escherichia coli. Cysteine (H226C) or serine (H226S) retain both normal activity and pH sensitivity, aspartate (H226D) shifts the pH profile toward basic pH, and alanine (H226A) inactivates the carrier at all pH values.”  Rimon A.et.al.   7592922
[10] “Oligomerization of NhaA, the Na+/H+ antiporter of Escherichia coli in the membrane and its functional and structural consequences.”  Gerchman Y.et.al.   11258962
[11] “Global topology analysis of the Escherichia coli inner membrane proteome.”  Daley D.O.et.al.   15919996
[12] “Monomers of the NhaA Na+/H+ antiporter of Escherichia coli are fully functional yet dimers are beneficial under extreme stress conditions at alkaline pH in the presence of Na+ or Li+.”  Rimon A.et.al.   17635927
[13] “Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH.”  Hunte C.et.al.   15988517
Structure:
1ZCD   3FI1   4ATV   4AU5     

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FASTA formatted sequence
1:	MKHLHRFFSS DASGGIILII AAILAMIMAN SGATSGWYHD FLETPVQLRV GSLEINKNML 
61:	LWINDALMAV FFLLVGLEVK RELMQGSLAS LRQAAFPVIA AIGGMIVPAL LYLAFNYADP 
121:	ITREGWAIPA ATDIAFALGV LALLGSRVPL ALKIFLMALA IIDDLGAIII IALFYTNDLS 
181:	MASLGVAAVA IAVLAVLNLC GARRTGVYIL VGVVLWTAVL KSGVHATLAG VIVGFFIPLK 
241:	EKHGRSPAKR LEHVLHPWVA YLILPLFAFA NAGVSLQGVT LDGLTSILPL GIIAGLLIGK 
301:	PLGISLFCWL ALRLKLAHLP EGTTYQQIMV VGILCGIGFT MSIFIASLAF GSVDPELINW 
361:	AKLGILVGSI SSAVIGYSWL RVRLRPSV