ArticleJournal of the American Society of Nephrology : JASN2008
Characterization of the sodium/hydrogen exchanger NHA2.
Article in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
The trial behind it
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
35 citing papers in PubMed, 76 citations in OpenAlex.
- 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
- Review
- NaInternational journal of molecular sciences · 2023Review
- Allosteric links between the hydrophilic N-terminus and transmembrane core of human NaProtein science : a publication of the Protein Society · 2022Article
- Structure, mechanism and lipid-mediated remodeling of the mammalian NaNature structural & molecular biology · 2022Article
- Landscape of sialylation patterns identify biomarkers for diagnosis and prediction of response to anti-TNF therapy in crohn's disease.Frontiers in genetics · 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
- Ethyl isopropyl amiloride decreases oxidative phosphorylation and increases mitochondrial fusion in clonal untransformed and cancer cells.American journal of physiology. Cell physiology · 2021Article
- The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer.International journal of molecular sciences · 2021Review
- Intracellular pH regulation: characterization and functional investigation of HBMC molecular and cell biology · 2021Article
- Sequence Features of Mitochondrial Transporter Protein Families.Biomolecules · 2020Review
- Physiological, Structural, and Functional Analysis of the Paralogous Cation-Proton Antiporters of NhaP Type fromInternational journal of molecular sciences · 2019Review
- NHA2 promotes cyst development in an in vitro model of polycystic kidney disease.The Journal of physiology · 2019Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Towards a Unified Understanding of Lithium Action in Basic Biology and its Significance for Applied Biology.The Journal of membrane biology · 2017Review
- NHA2 is expressed in distal nephron and regulated by dietary sodium.Journal of physiology and biochemistry · 2017Article
- Dissecting the proton transport pathway in electrogenic NaProceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cation/proton exchange has been recognized for decades in mammalian mitochondria, but the exchanger proteins have eluded identification. In this study, a cDNA from a human brain library, previously designated NHA2 in the genome, was cloned and characterized. The NHA2 transcript bears more similarity to prokaryotic than known eukaryotic sodium/proton exchangers, but it was found to be expressed in multiple mammalian organs and cultured cells. A mAb to NHA2 was generated and found to label an approximately 55-kD native protein in multiple tissues and cell lines. The specificity of this antibody was confirmed by demonstrating the loss of the native NHA2 band on immunoblots when cultured cells were treated with NHA2-specific small interfering RNA. Although NHA2 protein was detected in multiple organs, within each, its expression was restricted to specific cell types. In the kidney, co-localization with calbindin 28k and reverse transcription-PCR of microdissected tubules revealed that NHA2 is limited to the distal convoluted tubule. In cell lines, native NHA2 was localized both to the plasma membrane and to the intracellular compartment; immunogold electron microscopy of rat distal convoluted tubule demonstrated NHA2 predominantly but not exclusively on the inner mitochondrial membrane. Furthermore, co-sedimentation of NHA2 antigen and mitochondrial membranes was observed with differential centrifugation, and two mitochondrial markers co-localized with NHA2 in cultured cells. Regarding function, human NHA2 reversed the sodium/hydrogen exchanger-null phenotype when expressed in sodium/hydrogen exchanger-deficient yeast and restored the ability to defend high salinity in the presence of acidic extracellular pH. In summary, NHA2 is a ubiquitous mammalian sodium proton/exchanger that is restricted to the distal convoluted tubule in the kidney.
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Registered trials
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