Identification
Name:Na(+)/H(+) antiporter nhaA
Synonyms:
  • Sodium/proton antiporter nhaA
Gene Name:nhaA
Enzyme Class:Not Available
Biological Properties
General Function:Involved in sodium ion transport
Specific Function: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
Cellular Location:Cell inner membrane; Multi-pass membrane protein
SMPDB Pathways:Not Available
KEGG Pathways:Not Available
Transports:
Transport References:
  • Orth, J. D., Conrad, T. M., Na, J., Lerman, J. A., Nam, H., Feist, A. M., Palsson, B. O. (2011). "A comprehensive genome-scale reconstruction of Escherichia coli metabolism--2011." Mol Syst Biol 7:535. Pubmed: 21988831
Metabolites:
ECMDB IDNameView
ECMDB21225Hydrogen ionMetaboCard
ECMDB02908SodiumMetaboCard
GO Classification:
Component
cell part
integral to membrane
intrinsic to membrane
membrane part
Process
biological regulation
cation homeostasis
cation transport
chemical homeostasis
establishment of localization
homeostatic process
ion homeostasis
ion transport
monovalent inorganic cation homeostasis
monovalent inorganic cation transport
regulation of biological quality
regulation of pH
sodium ion transport
transport
Gene Properties
Blattner:b0019
Gene OrientationClockwise
Centisome Percentage:0.38
Left Sequence End17489
Right Sequence End18655
Gene Sequence:
>1167 bp
GTGAAACATCTGCATCGATTCTTTAGCAGTGATGCCTCGGGAGGCATTATTCTTATCATT
GCCGCTATCCTGGCGATGATTATGGCCAACAGCGGCGCAACCAGTGGATGGTATCACGAC
TTTCTGGAGACGCCGGTTCAGCTCCGGGTTGGTTCACTCGAAATCAACAAAAACATGCTG
TTATGGATAAATGACGCGCTGATGGCGGTATTTTTCCTGTTAGTCGGTCTGGAAGTTAAA
CGTGAACTGATGCAAGGATCGCTAGCCAGCTTACGCCAGGCCGCATTTCCAGTTATCGCC
GCTATTGGTGGGATGATTGTGCCGGCATTACTCTATCTGGCTTTTAACTATGCCGATCCG
ATTACCCGCGAAGGGTGGGCGATCCCGGCGGCTACTGACATTGCTTTTGCACTTGGTGTA
CTGGCGCTGTTGGGAAGTCGTGTTCCGTTAGCGCTGAAGATCTTTTTGATGGCTCTGGCT
ATTATCGACGATCTTGGGGCCATCATTATCATCGCATTGTTCTACACTAATGACTTATCG
ATGGCCTCTCTTGGCGTCGCGGCTGTAGCAATTGCGGTACTCGCGGTATTGAATCTGTGT
GGTGCACGCCGCACGGGCGTCTATATTCTTGTTGGCGTGGTGTTGTGGACTGCGGTGTTG
AAATCGGGGGTTCACGCAACTCTGGCGGGGGTAATTGTCGGCTTCTTTATTCCTTTGAAA
GAGAAGCATGGGCGTTCTCCAGCGAAGCGACTGGAGCATGTGTTGCACCCGTGGGTGGCG
TATCTGATTTTGCCGCTGTTTGCATTTGCTAATGCTGGCGTTTCACTGCAAGGCGTCACG
CTGGATGGCTTGACCTCCATTCTGCCATTGGGGATCATCGCTGGCTTGCTGATTGGCAAA
CCGCTGGGGATTAGTCTGTTCTGCTGGTTGGCGCTGCGTTTGAAACTGGCGCATCTGCCT
GAGGGAACGACTTATCAGCAAATTATGGTGGTGGGGATCCTGTGCGGTATCGGTTTTACT
ATGTCTATCTTTATTGCCAGCCTGGCCTTTGGTAGCGTAGATCCAGAACTGATTAACTGG
GCGAAACTCGGTATCCTGGTCGGTTCTATCTCTTCGGCGGTAATTGGATACAGCTGGTTA
CGCGTTCGTTTGCGTCCATCAGTTTGA
Protein Properties
Pfam Domain Function:
Protein Residues:388
Protein Molecular Weight:41355
Protein Theoretical pI:10
Signaling Regions:
  • None
Transmembrane Regions:
  • 12-30
  • 59-85
  • 95-116
  • 121-143
  • 150-175
  • 182-200
  • 205-218
  • 223-236
  • 247-271
  • 290-311
  • 327-350
  • 357-382
Protein Sequence:
>Na(+)/H(+) antiporter nhaA
MKHLHRFFSSDASGGIILIIAAILAMIMANSGATSGWYHDFLETPVQLRVGSLEINKNML
LWINDALMAVFFLLVGLEVKRELMQGSLASLRQAAFPVIAAIGGMIVPALLYLAFNYADP
ITREGWAIPAATDIAFALGVLALLGSRVPLALKIFLMALAIIDDLGAIIIIALFYTNDLS
MASLGVAAVAIAVLAVLNLCGARRTGVYILVGVVLWTAVLKSGVHATLAGVIVGFFIPLK
EKHGRSPAKRLEHVLHPWVAYLILPLFAFANAGVSLQGVTLDGLTSILPLGIIAGLLIGK
PLGISLFCWLALRLKLAHLPEGTTYQQIMVVGILCGIGFTMSIFIASLAFGSVDPELINW
AKLGILVGSISSAVIGYSWLRVRLRPSV
References
External Links:
ResourceLink
Uniprot ID:P13738
Uniprot Name:NHAA_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:21321905
Ecogene ID:EG10652
Ecocyc:EG10652
ColiBase:b0019
Kegg Gene:b0019
EchoBASE ID:EB0646
CCDB:NHAA_ECOLI
BacMap:16128013
General Reference:
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Daley, D. O., Rapp, M., Granseth, E., Melen, K., Drew, D., von Heijne, G. (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308:1321-1323. Pubmed: 15919996
  • 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 90:1212-1216. Pubmed: 8381959
  • 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 40:3403-3412. Pubmed: 11258962
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • 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 435:1197-1202. Pubmed: 15988517
  • 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 363:264-268. Pubmed: 7737413
  • 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 266:21753-21759. Pubmed: 1657980
  • 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 263:10408-10414. Pubmed: 2839489
  • Rimon, A., Gerchman, Y., Olami, Y., Schuldiner, S., Padan, E. (1995). "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." J Biol Chem 270:26813-26817. Pubmed: 7592922
  • Rimon, A., Tzubery, T., Padan, E. (2007). "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+." J Biol Chem 282:26810-26821. Pubmed: 17635927
  • Taglicht, D., Padan, E., Schuldiner, S. (1991). "Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli." J Biol Chem 266:11289-11294. Pubmed: 1645730
  • Yura, T., Mori, H., Nagai, H., Nagata, T., Ishihama, A., Fujita, N., Isono, K., Mizobuchi, K., Nakata, A. (1992). "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region." Nucleic Acids Res 20:3305-3308. Pubmed: 1630901