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Protein

Na(+)/H(+) antiporter NhaA

Gene

nhaA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Na+/H+ antiporter that extrudes sodium in exchange for external protons. Catalyzes the exchange of 2 H+ per Na+. Can mediate sodium uptake when a transmembrane pH gradient is applied. Active at alkaline pH. Activity is strongly down-regulated below pH 6.5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei133 – 1331Essential for antiport activity
Sitei163 – 1642Essential for antiport activity
Sitei163 – 1631Essential for antiport activity
Sitei241 – 2411Important for pH sensorCurated
Sitei249 – 2491Important for pH sensorCurated
Sitei252 – 2521Important for pH sensorCurated

GO - Molecular functioni

GO - Biological processi

  • cation transmembrane transport Source: GOC
  • proton transport Source: EcoCyc
  • regulation of pH Source: InterPro
  • sodium ion transport Source: EcoCyc
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

BioCyciEcoCyc:NHAA-MONOMER.
ECOL316407:JW0018-MONOMER.
MetaCyc:NHAA-MONOMER.

Protein family/group databases

TCDBi2.A.33.1.1. the nhaa na(+):h(+) antiporter (nhaa) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Na(+)/H(+) antiporter NhaA
Alternative name(s):
Sodium/proton antiporter NhaA
Gene namesi
Name:nhaA
Synonyms:ant
Ordered Locus Names:b0019, JW0018
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10652. nhaA.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111Cytoplasmic1 PublicationAdd
BLAST
Transmembranei12 – 3019Helical; Name=1Add
BLAST
Topological domaini31 – 5828Periplasmic1 PublicationAdd
BLAST
Transmembranei59 – 8527Helical; Name=2Add
BLAST
Topological domaini86 – 949Cytoplasmic1 Publication
Transmembranei95 – 11622Helical; Name=3Add
BLAST
Topological domaini117 – 1204Periplasmic1 Publication
Transmembranei121 – 14323Helical; Name=4Add
BLAST
Topological domaini144 – 1496Cytoplasmic1 Publication
Transmembranei150 – 17526Helical; Name=5Add
BLAST
Topological domaini176 – 1816Periplasmic1 Publication
Transmembranei182 – 20019Helical; Name=6Add
BLAST
Topological domaini201 – 2044Cytoplasmic1 Publication
Transmembranei205 – 21814Helical; Name=7Add
BLAST
Topological domaini219 – 2224Periplasmic1 Publication
Transmembranei223 – 23614Helical; Name=8Add
BLAST
Topological domaini237 – 24610Cytoplasmic1 Publication
Transmembranei247 – 27125Helical; Name=9Add
BLAST
Topological domaini272 – 28918Periplasmic1 PublicationAdd
BLAST
Transmembranei290 – 31122Helical; Name=10Add
BLAST
Topological domaini312 – 32615Cytoplasmic1 PublicationAdd
BLAST
Transmembranei327 – 35024Helical; Name=11Add
BLAST
Topological domaini351 – 3566Periplasmic1 Publication
Transmembranei357 – 38226Helical; Name=12Add
BLAST
Topological domaini383 – 3886Cytoplasmic1 Publication

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: EcoCyc
  • plasma membrane Source: EcoCyc
Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331D → N: Loss of antiport activity. Abolishes ability to grow on high salt medium. 1 Publication
Mutagenesisi163 – 1631D → C: Loss of antiport activity. 2 Publications
Mutagenesisi163 – 1631D → N: Loss of antiport activity. Abolishes ability to grow on high salt medium. 2 Publications
Mutagenesisi164 – 1641D → N: Loss of antiport activity. Abolishes ability to grow on high salt medium. 1 Publication
Mutagenesisi225 – 2251H → A: Loss of antiport activity. Abolishes ability to grow at alkaline pH. 2 Publications
Mutagenesisi225 – 2251H → C or S: Slightly reduced antiport activity. No effect on pH sensitivity. 2 Publications
Mutagenesisi225 – 2251H → D or R: Shifts threshold for pH-sensitive inactivation. 2 Publications
Mutagenesisi338 – 3381G → S: Loss of pH-sensitivity. 1 Publication

Chemistry

ChEMBLiCHEMBL5478.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 388388Na(+)/H(+) antiporter NhaAPRO_0000052410Add
BLAST

Proteomic databases

PaxDbiP13738.

Expressioni

Inductioni

Transcription stimulated by high Na+ concentrations.

Interactioni

Subunit structurei

Monomer and homodimer.2 Publications

Protein-protein interaction databases

BioGridi4259720. 28 interactions.
DIPiDIP-10335N.
STRINGi511145.b0019.

Chemistry

BindingDBiP13738.

Structurei

Secondary structure

1
388
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi13 – 3018Combined sources
Beta strandi32 – 343Combined sources
Helixi35 – 417Combined sources
Beta strandi45 – 506Combined sources
Beta strandi53 – 586Combined sources
Helixi59 – 8426Combined sources
Turni86 – 883Combined sources
Turni91 – 933Combined sources
Helixi95 – 10410Combined sources
Turni105 – 1084Combined sources
Helixi109 – 1124Combined sources
Helixi113 – 1153Combined sources
Helixi122 – 1254Combined sources
Beta strandi127 – 1304Combined sources
Helixi134 – 1429Combined sources
Beta strandi146 – 1483Combined sources
Beta strandi150 – 1523Combined sources
Helixi153 – 17422Combined sources
Helixi181 – 19919Combined sources
Helixi206 – 21813Combined sources
Turni219 – 2213Combined sources
Helixi223 – 23614Combined sources
Helixi241 – 2433Combined sources
Helixi247 – 26115Combined sources
Helixi263 – 2719Combined sources
Beta strandi277 – 2793Combined sources
Helixi284 – 2874Combined sources
Turni290 – 2934Combined sources
Helixi294 – 2985Combined sources
Helixi301 – 3033Combined sources
Turni305 – 3117Combined sources
Turni315 – 3173Combined sources
Helixi325 – 3284Combined sources
Helixi331 – 3344Combined sources
Helixi339 – 34911Combined sources
Turni351 – 3533Combined sources
Helixi358 – 37013Combined sources
Turni375 – 3773Combined sources
Helixi378 – 3803Combined sources
Turni381 – 3833Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZCDX-ray3.45A/B1-388[»]
3FI1electron microscopy7.00A9-384[»]
4ATVX-ray3.50A/B/C/D1-388[»]
4AU5X-ray3.70A/B/C/D1-388[»]
ProteinModelPortaliP13738.
SMRiP13738. Positions 9-384.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13738.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni45 – 5814Important for dimerizationAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105DRC. Bacteria.
COG3004. LUCA.
HOGENOMiHOG000218489.
InParanoidiP13738.
KOiK03313.
OMAiQKAIFPA.
OrthoDBiEOG61VZ7F.
PhylomeDBiP13738.

Family and domain databases

Gene3Di1.20.1530.10. 1 hit.
HAMAPiMF_01844. NhaA.
InterProiIPR023171. Na/H_antiporter_dom.
IPR004670. NhaA.
[Graphical view]
PANTHERiPTHR30341:SF0. PTHR30341:SF0. 1 hit.
PfamiPF06965. Na_H_antiport_1. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00773. NhaA. 1 hit.

Sequencei

Sequence statusi: Complete.

P13738-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKHLHRFFSS DASGGIILII AAILAMIMAN SGATSGWYHD FLETPVQLRV
60 70 80 90 100
GSLEINKNML LWINDALMAV FFLLVGLEVK RELMQGSLAS LRQAAFPVIA
110 120 130 140 150
AIGGMIVPAL LYLAFNYADP ITREGWAIPA ATDIAFALGV LALLGSRVPL
160 170 180 190 200
ALKIFLMALA IIDDLGAIII IALFYTNDLS MASLGVAAVA IAVLAVLNLC
210 220 230 240 250
GARRTGVYIL VGVVLWTAVL KSGVHATLAG VIVGFFIPLK EKHGRSPAKR
260 270 280 290 300
LEHVLHPWVA YLILPLFAFA NAGVSLQGVT LDGLTSILPL GIIAGLLIGK
310 320 330 340 350
PLGISLFCWL ALRLKLAHLP EGTTYQQIMV VGILCGIGFT MSIFIASLAF
360 370 380
GSVDPELINW AKLGILVGSI SSAVIGYSWL RVRLRPSV
Length:388
Mass (Da):41,356
Last modified:February 1, 1996 - v3
Checksum:iB508B1D2E5EE9130
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03879 Genomic DNA. Translation: AAA23448.2.
U00096 Genomic DNA. Translation: AAC73130.1.
AP009048 Genomic DNA. Translation: BAB96592.1.
S67239 Genomic DNA. Translation: AAB20348.1.
PIRiC64722.
RefSeqiNP_414560.1. NC_000913.3.
WP_000681354.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC73130; AAC73130; b0019.
BAB96592; BAB96592; BAB96592.
GeneIDi944758.
KEGGiecj:JW0018.
eco:b0019.
PATRICi32115129. VBIEscCol129921_0016.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03879 Genomic DNA. Translation: AAA23448.2.
U00096 Genomic DNA. Translation: AAC73130.1.
AP009048 Genomic DNA. Translation: BAB96592.1.
S67239 Genomic DNA. Translation: AAB20348.1.
PIRiC64722.
RefSeqiNP_414560.1. NC_000913.3.
WP_000681354.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZCDX-ray3.45A/B1-388[»]
3FI1electron microscopy7.00A9-384[»]
4ATVX-ray3.50A/B/C/D1-388[»]
4AU5X-ray3.70A/B/C/D1-388[»]
ProteinModelPortaliP13738.
SMRiP13738. Positions 9-384.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4259720. 28 interactions.
DIPiDIP-10335N.
STRINGi511145.b0019.

Chemistry

BindingDBiP13738.
ChEMBLiCHEMBL5478.

Protein family/group databases

TCDBi2.A.33.1.1. the nhaa na(+):h(+) antiporter (nhaa) family.

Proteomic databases

PaxDbiP13738.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73130; AAC73130; b0019.
BAB96592; BAB96592; BAB96592.
GeneIDi944758.
KEGGiecj:JW0018.
eco:b0019.
PATRICi32115129. VBIEscCol129921_0016.

Organism-specific databases

EchoBASEiEB0646.
EcoGeneiEG10652. nhaA.

Phylogenomic databases

eggNOGiENOG4105DRC. Bacteria.
COG3004. LUCA.
HOGENOMiHOG000218489.
InParanoidiP13738.
KOiK03313.
OMAiQKAIFPA.
OrthoDBiEOG61VZ7F.
PhylomeDBiP13738.

Enzyme and pathway databases

BioCyciEcoCyc:NHAA-MONOMER.
ECOL316407:JW0018-MONOMER.
MetaCyc:NHAA-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP13738.
PROiP13738.

Family and domain databases

Gene3Di1.20.1530.10. 1 hit.
HAMAPiMF_01844. NhaA.
InterProiIPR023171. Na/H_antiporter_dom.
IPR004670. NhaA.
[Graphical view]
PANTHERiPTHR30341:SF0. PTHR30341:SF0. 1 hit.
PfamiPF06965. Na_H_antiport_1. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00773. NhaA. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli."
    Karpel R., Olami Y., Taglicht D., Schuldiner S., Padan E.
    J. Biol. Chem. 263:10408-10414(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Padan E.
    Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  3. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
    Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
    Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  6. "Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions."
    Karpel R., Alon T., Glaser G., Schuldiner S., Padan E.
    J. Biol. Chem. 266:21753-21759(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
  7. "Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli."
    Taglicht D., Padan E., Schuldiner S.
    J. Biol. Chem. 266:11289-11294(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PARTIAL PROTEIN SEQUENCE.
  8. "Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli."
    Gerchman Y., Olami Y., Rimon A., Taglicht D., Schuldiner S., Padan E.
    Proc. Natl. Acad. Sci. U.S.A. 90:1212-1216(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
  9. "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., Noumi T., Tsuchiya T., Kanazawa H.
    FEBS Lett. 363:264-268(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-133; ASP-163 AND ASP-164.
  10. "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., Gerchman Y., Olami Y., Schuldiner S., Padan E.
    J. Biol. Chem. 270:26813-26817(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-225.
  11. "Oligomerization of NhaA, the Na+/H+ antiporter of Escherichia coli in the membrane and its functional and structural consequences."
    Gerchman Y., Rimon A., Venturi M., Padan E.
    Biochemistry 40:3403-3412(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, MUTAGENESIS OF ASP-163; HIS-225 AND GLY-338.
  12. "Global topology analysis of the Escherichia coli inner membrane proteome."
    Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.
    Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
    Strain: K12 / MG1655 / ATCC 47076.
  13. "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., Tzubery T., Padan E.
    J. Biol. Chem. 282:26810-26821(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  14. "Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH."
    Hunte C., Screpanti E., Venturi M., Rimon A., Padan E., Michel H.
    Nature 435:1197-1202(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS).

Entry informationi

Entry nameiNHAA_ECOLI
AccessioniPrimary (citable) accession number: P13738
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 1, 1996
Last modified: May 11, 2016
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.