ArticleProceedings of the National Academy of Sciences of the United States of America2007
A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.Neurology · 2015Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Trafficking of the human NaProtein science : a publication of the Protein Society · 2026Article
- Structure and Inhibition of the Human NaInternational journal of molecular sciences · 2025Article
- Residues R177 and S178 of the human NaFEBS letters · 2025Article
- The crossing of two unwound transmembrane regions that is the hallmark of the NhaA structural fold is critical for antiporter activity.Scientific reports · 2024Article
- NaInternational journal of molecular sciences · 2023Review
- Control of intracellular pH and bicarbonate by CONature communications · 2023Article
- Human pathogenic bacteria on high-touch dry surfaces can be controlled by warming to human-skin temperature under moderate humidity.PloS one · 2023Article
- Allosteric links between the hydrophilic N-terminus and transmembrane core of human NaProtein science : a publication of the Protein Society · 2022Article
- The Physiological Function and Potential Role of the Ubiquitous NaInternational journal of molecular sciences · 2022Review
- Prokaryotic NaInternational journal of molecular sciences · 2022Review
- Heterologous (Over) Expression of Human SoLute Carrier (SLC) in Yeast: A Well-Recognized Tool for Human Transporter Function/Structure Studies.Life (Basel, Switzerland) · 2022Review
- Structure, mechanism and lipid-mediated remodeling of the mammalian NaNature structural & molecular biology · 2022Article
- The Less Well-Known Little Brothers: The SLC9B/NHA Sodium Proton Exchanger Subfamily-Structure, Function, Regulation and Potential Drug-Target Approaches.Frontiers in physiology · 2022Review
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Intracellular pH regulation: characterization and functional investigation of HBMC molecular and cell biology · 2021Article
- NaInternational journal of molecular sciences · 2021Article
- Characterization of T-DM1-resistant breast cancer cells.Pharmacology research & perspectives · 2020Article
- Inhibition of Sodium-Hydrogen Antiport by Antibodies to NHA1 in Brush Border Membrane Vesicles from Whole Aedes aegypti Larvae.The Journal of membrane biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Phylogenetic analysis of the cation/proton antiporter superfamily has uncovered a previously unknown clade of genes in metazoan genomes, including two previously uncharacterized human isoforms, NHA1 and NHA2, found in tandem on human chromosome 4. The NHA (sodium hydrogen antiporter) family members share significant sequence similarity with Escherichia coli NhaA, including a conserved double aspartate motif in predicted transmembrane 5. We show that HsNHA2 (Homo sapiens NHA2) resides on the plasma membrane and, in polarized MDCK cells, localizes to the apical domain. Analysis of mouse tissues indicates that NHA2 is ubiquitous. When expressed in the yeast Saccharomyces cerevisiae lacking endogenous cation/proton antiporters and pumps, HsNHA2 can confer tolerance to Li(+) and Na(+) ions but not to K(+). HsNHA2 transformants accumulated less Li(+) than the salt-sensitive host; however, mutagenic replacement of the conserved aspartates abolished all observed phenotypes. Functional complementation by HsNHA2 was insensitive to amiloride, a characteristic inhibitor of plasma membrane sodium hydrogen exchanger isoforms, but was inhibited by phloretin. These are hallmarks of sodium-lithium countertransport activity, a highly heritable trait correlating with hypertension. Our findings raise the possibility that NHA genes may contribute to sodium-lithium countertransport activity and salt homeostasis in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.