Figure 1.

The amino acid sequence and schematic topology of the human voltage-gated proton channel, hH_V1. Within the TM domain, acidic residues are red, basic residues are blue, aromatic residues are orange, and polar residues are gray. Specific amino acids of note, beginning at the N terminus: deletion of 1–20 (green) produces a “short” isoform common in malignant B cells (Hondares et al., 2014); Thr²⁹ is a PKC phosphorylation site responsible for enhanced gating (Musset et al., 2010a); M91T is the first identified hH_V1 mutation (Iovannisci et al., 2010); Asp¹¹² is crucial to H⁺ selectivity (Musset et al., 2011); His¹⁴⁰ and His¹⁹³ coordinate Zn²⁺ binding (Ramsey et al., 2006); the three Arg in S4 are thought to open the conductance pathway in response to voltage (Ramsey et al., 2006; Sasaki et al., 2006; Gonzalez et al., 2013); and the C terminus has an extensive coiled-coil region (black) that holds the dimer together (Koch et al., 2008; Lee et al., 2008; Tombola et al., 2008; Fujiwara et al., 2014). The image was drawn with TOPO2 (Johns, 2016).