ArticleNature2006
A voltage-gated proton-selective channel lacking the pore domain.
Article in Nature, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 378 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
378 citing papers in PubMed.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- Bdelloid rotifers harbor a voltage-gated proton channel with distinct mechanistic features.Nature communications · 2026Article
- Human Nasal and Bronchial Epithelium in Cystic Fibrosis: Differences in Expression of Airway pH Regulatory Proteins.Pediatric pulmonology · 2026Article
- Amyloid precursor protein is a subunit of microglial Hv1 channels.Current opinion in immunology · 2026Review
- Article
- Voltage-gated proton channel Hv1/VSOP regulates reciprocal interactions between F-actin and endosomes in microglia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proton-selective conductance and gating of the lysosomal cation channel TMEM175.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spatially Resolved Mapping of Voltage-Gated Proton Channel Activity Reveals Delayed Proton Transport in Local Microenvironments.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interrogating the structure and function of the human voltage-gated proton channel (hHbioRxiv : the preprint server for biology · 2025Article
- Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure-guided discovery of Otopetrin 1 inhibitors reveals druggable binding sites at the intrasubunit interface.Nature communications · 2025Article
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025Review
- Modular architecture of KEMBO reports · 2025Review
- Expression and Purification of the Human Voltage-Gated Proton Channel (hHBio-protocol · 2025Article
- A novel method for expressing and purifying large quantities of functional and stable human voltage-gated proton channel (hHProtein science : a publication of the Protein Society · 2025Article
- Biophysical Properties of Somatic Cancer Mutations in the S4 Transmembrane Segment of the Human Voltage-Gated Proton Channel hHBiomolecules · 2025Article
- Fluctuating hydrogen-bond network of the Hv1 ion channel.Computational and structural biotechnology journal · 2025Article
- Validation of HvFrontiers in cellular neuroscience · 2025Article
- Dimerization is required for the glycosylation of S1-S2 linker of sea urchin voltage-gated proton channel Hv1.Biophysical journal · 2024Article
318 more citing papers are in PubMed but not listed here.
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.
Funding
Abstract
Voltage changes across the cell membrane control the gating of many cation-selective ion channels. Conserved from bacteria to humans, the voltage-gated-ligand superfamily of ion channels are encoded as polypeptide chains of six transmembrane-spanning segments (S1-S6). S1-S4 functions as a self-contained voltage-sensing domain (VSD), in essence a positively charged lever that moves in response to voltage changes. The VSD 'ligand' transmits force via a linker to the S5-S6 pore domain 'receptor', thereby opening or closing the channel. The ascidian VSD protein Ci-VSP gates a phosphatase activity rather than a channel pore, indicating that VSDs function independently of ion channels. Here we describe a mammalian VSD protein (H(V)1) that lacks a discernible pore domain but is sufficient for expression of a voltage-sensitive proton-selective ion channel activity. H(v)1 currents are activated at depolarizing voltages, sensitive to the transmembrane pH gradient, H+-selective, and Zn2+-sensitive. Mutagenesis of H(v)1 identified three arginine residues in S4 that regulate channel gating and two histidine residues that are required for extracellular inhibition of H(v)1 by Zn2+. H(v)1 is expressed in immune tissues and manifests the characteristic properties of native proton conductances (G(vH+)). In phagocytic leukocytes, G(vH+) are required to support the oxidative burst that underlies microbial killing by the innate immune system. The data presented here identify H(v)1 as a long-sought voltage-gated H+ channel and establish H(v)1 as the founding member of a family of mammalian VSD proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.