TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.51.1.1









The voltage-gated proton channel, mVSOP (269 aas) (Sasaki et al., 2006).  A hydrophobic plug functions as the gate (Chamberlin et al. 2013).

Eukaryota
Metazoa
mVSOP of Mus musculus (Q9DCE4)
*1.A.51.1.2









The voltage-gated proton channel, Hv1, Hv1 or HVCN1 (273 aas) (Ramsey et al., 2006). Thr29 is a phosphorylation site that activates the HVCN1 channel in leukocytes (Musset et al., 2010). The condctivity pore has been delineated and depends of a carboxyl group (Asp or Glu) in the channel (Morgan et al. 2013). The four transmembrane helices sense voltage and the pH gradient, and conduct protons exclusively. Selectivity is achieved by the unique ability of H3O+ to protonate an Asp-Arg salt bridge. Pathognomonic sensitivity of gating to the pH gradient ensures HV1 channel opening only when acid extrusion will result, which is crucial to its biological functions (DeCoursey 2015). An exception occurs in dinoflagellates (see 1.A.51.1.4) in which H+ influx through HV1 triggers a bioluminescent flash. The gating mechanism of Hv1, cooperativity within dimers and the sensitivity to metal ions have been reviewed (Okamura et al. 2015). How this channel is activated by cytoplasmic [H+] and depolarization of the membrane potential has been proposed by Castillo et al. 2015. The extracellular ends of the first transmembrane segments form the intersubunit interface that mediates coupling between binding sites, while the coiled-coil domain does not directly participate in the process (Hong et al. 2015). Deep water penetration through hHv1 has been observed, suggesting a highly focused electric field, comprising two helical turns along the fourth TMS. This region likely contains the H+ selectivity filter and the conduction pore. A 3D model offers an explicit mechanism for voltage activation based on a one-click sliding helix conformational rearrangement (Li et al. 2015).  Trp-207 enables four characteristic properties: slow channel opening, highly temperature-dependent gating kinetics, proton selectivity, and ΔpH-dependent gating (Cherny et al. 2015).  The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively (Okuda et al. 2016).  Segment S3 plays a role in activating gating (Sakata et al. 2016).  Two sites have been identified: one is the binding pocket of 2GBI (accessible to ligands from the intracellular side); the other is located at the exit site of the proton permeation pathway (Gianti et al. 2016).

Eukaryota
Metazoa
Hv1 of Homo sapiens (Q96D96)
*1.A.51.1.3









Voltage-gated proton channel, HvCN1; VSOP; VSX1 (Sasaki et al., 2006).  Exhibits voltage and pH-dependent gating as well as Zn2+-reactivity. In the dimeric strcuture, each subumit has a proton channel. TMS4 appears to be the voltage sensor.  Subunit cooperativity has been demonstrated (Gonzalez et al. 2010).

 

 

Eukaryota
Metazoa
HvCN1 of Ciona intestinalis (Q1JV40)
*1.A.51.1.4









Voltage-gated proton-specific monomeric channel, kHv1. Activated by depolarization; functions in signaling and excitability to trigger bioluminescence (Smith et al., 2011).  Hv1 most likely forms an internal water wire for selective proton transfer, and interactions between water molecules and S4 arginines may underlie coupling between voltage- and pH-gradient sensing (Ramsey et al. 2010).

Eukaryota
Dinophyceae
kHv1 of Karlodinium veneficum (G5CPN9)
*1.A.51.1.5









Proton channel protein, NpHv1 of 239 aas and 4 TMSs.  Proton selectivity, and pH- and voltage-dependent gating have been demoonstrated. Mutations in the first transmembrane segment at position 66 (Asp66), the presumed selectivity filter, led to a loss of proton-selective conduction (Chaves et al. 2016).

Eukaryota
Metazoa
NpHv1 of Nicoletia phytophila
*1.A.51.2.1









The voltage-sensor containing phosphatase, VSP, of 576 aas and 4 TMSs N-terminal to the phosphatase domain. The enzyme region of VSP contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. The coupling between the two domains has been studied (Sakata et al. 2017).

 

Eukaryota
Metazoa
VSP of Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis)