Journal Article FZJ-2026-04932

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A large family of unusual voltage‐sensing proton channels (Hv3) in mollusks

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2026
Wiley-Blackwell Oxford [u.a.]

The FEBS journal 357, febs.70617 () [10.1111/febs.70617]

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Abstract: Mollusks exhibit an unusually high diversity of genes encodingvoltage-gated proton channel homologs. In addition to the conventionalproton channels Hv1, Hv2, and Hv4, a structurally and functionally atypicalproton channel was previously identified in Aplysia californica (AcHv3,subsequently renamed AcHv3.1). A comprehensive analysis of cDNA, transcriptomeshotgun assembly (TSA) and genomic databases revealed numerousorthologous and paralogous Hv3-like sequences in Aplysia and acrossall other molluscan species analyzed. These Hv3-like channels share canonicalfeatures of voltage-gated proton channels, including four transmembranespanning segments (S1–S4), a negatively charged residue in S1responsible for proton selectivity, a conserved voltage-sensing motif in S4containing positively charged arginine residues and a fully conserved tryptophanresidue. However, Hv3-like channels differ markedly from conventionalHv channels in possessing much larger intracellular N- andC-terminal domains, an elongated extracellular loop between S1 and S2and a reduced number of gating charges in S4, with only two arginine residues(or a single arginine in the case of Hv3.6 channels) compared to threein canonical Hv channels. In addition, Hv3-like channels contain a uniqueproline residue within S4, forming a characteristic PWRxxR motif. Basedon structural differences, including putative PDZ-Binding motifs and spacingof transmembrane cysteine residues, together with molecular distancetree analyses, a classification into seven subfamilies (Hv3.1-Hv3.7) is proposed.Some of these subfamilies were found only in Gastropoda or Bivalvia,while others were identified in all molluscan classes. AlthoughGFP-tagged AcHv3.1, AcHv3.2, and AcHv3.5 localized to the plasmamembrane, only AcHv3.1 generated detectable proton currents.

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Contributing Institute(s):
  1. Molekular- und Zellphysiologie (IBI-1)
Research Program(s):
  1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026
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Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-10-09, last modified 2026-10-09


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