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Voltage-gated proton channel (Hv1) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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The voltage-gated proton channel (provisionally denoted Hv1) is a putative 4TM proton-selective channel gated by membrane depolarization and which is sensitive to the transmembrane pH gradient [1,5-6,29,31]. The structure of Hv1 is homologous to the voltage sensing domain (VSD) of the superfamily of voltage-gated ion channels (i.e. segments S1 to S4) and contains no discernable pore region [29,31]. Proton flux through Hv1 is instead most likely mediated by a hydrogen-bonded chain [4,25] formed in a crevice of the protein when the voltage-sensing S4 helix moves in response to a change in transmembrane potential [28,37]. Proton selective conduction requires an aspartate residue at the center of the pore [2,24,33]. Both selectivity and conduction may result from obligatory protonation by each conducted proton [8,11]. Hv1 expresses largely as a dimer mediated by intracellular C-terminal coiled-coil interactions [19] but individual promoters nonetheless support gated H+ flux via separate conduction pathways [17-18,26,34]. Within dimeric structures, the two protomers do not function independently, but display co-operative interactions during gating resulting in increased voltage sensitivity, but slower activation, of the dimeric, versus monomeric, complexes [13,35]. The otopetrin proteins appear to form proton-selective ion channels and to date 3 subtypes have been identified in eukaryotes; otopetrin 1 [27,36], otopetrin 2 [20] and otopetrin 3 [15].

Channels and Subunits

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Hv1 C Show summary »

Target Id 746
Nomenclature Hv1
Previous and unofficial names Voltage-gated proton channel 1 (HVCN1) | Voltage-sensor only protein (VSOP) | BTS | hydrogen voltage-gated channel 1
Genes HVCN1 (Hs), Hvcn1 (Mm), Hvcn1 (Rn)
Ensembl ID ENSG00000122986 (Hs), ENSMUSG00000064267 (Mm), ENSRNOG00000001270 (Rn)
UniProtKB AC Q96D96 (Hs), Q3U2S8 (Mm)
Channel blockers
Zn2+ pIC50 ~5.7 – 6.3
Cd2+ pIC50 ~5.0
Functional characteristics Activated by membrane depolarization mediating macroscopic currents with time-, voltage- and pH-dependence; outwardly rectifying; voltage dependent kinetics with relatively slow current activation sensitive to extracellular pH and temperature, relatively fast deactivation; voltage threshold for current activation determined by pH gradient (ΔpH = pHo -pHi) across the membrane


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Further reading

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How to cite this family page

Database page citation:

Voltage-gated proton channel (Hv1). Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.