Disease relevance of KHA1

• The hydrophobic, but not the hydrophilic, domain of plant CHX is remarkably similar to monovalent cation/proton antiporter-2 (CPA2) proteins, especially yeast (Saccharomyces cerevisiae) KHA1 and Synechocystis NhaS4 [1].

High impact information on KHA1

• One of the transporters formerly believed to extrude K+ from the yeast cells (besides Ena1-4p and Nha1p) was named Kha1p and presumed as a putative plasma membrane K+/H+ antiporter [2].
• We prepared kha1 and tok1-kha1 deletion strains in the B31 and MAB 2d background [2].
• Based on these findings, Kha1p is probably not localized in plasma membrane and does not mediate efflux of alkali metal cations from cells, but is important for the regulation of intracellular cation homeostasis and optimal pH control, similarly as the Nhx1p [2].
• Fluorescence microscopy of green fluorescent protein (GFP)-tagged Kha1p showed that this antiporter is localized preferentially intracellularly (in contrast to the plasma membrane Na+/H+ antiporter Nha1p) [2].
• We performed a large physiological study with these strains to specify the phenotype of kha1 deletion [2].

Biological context of KHA1

• The KHA1 gene corresponding to the open reading frame YJL094c (2.62 kb) encoding a putative K+/H+ antiporter (873 amino acids) in Saccharomyces cerevisiae was disrupted by homologous recombination [3].
• Reports of characterized fungal and prokaryotic CPA2 indicate that they have various transport modes, including K(+)/H(+) (KHA1), Na(+)/H(+)-K(+) (GerN) antiport, and ligand-gated ion channel (KefC) [1].
• Based on the deduced amino acid sequence, the Kha1 protein can be classified as a Na+/H+ transporter since it has a large N-terminal domain similar to the family of NHEs (Na+/H+ exchangers) [4].
• The Saccharomyces cerevisiae genome contains three genes encoding alkali metal cation/H+ antiporters (Nha1p, Nhx1p, Kha1p) that differ in cell localization, substrate specificity and physiological function [5].

Associations of KHA1 with chemical compounds

• Disruption of the KHA1 gene resulted in an increased K+ accumulation and net influx without a significant difference in efflux, as well as an increased growth rate, smaller cells, and twice the cell yield per glucose used [3].
• Two main phenotype manifestations of the kha1 deletion were growth defect on high external pH and hygromycin sensitivity [2].
• The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p [4].

Other interactions of KHA1

• Deletion mutants of the two unknown genes J0909 and J0911 are viable [6].
• Functional substitution for Gef1p was, however, achieved in the presence of an increased level of intact or C-terminally truncated yeast Kha1 protein [4].

References