Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that Candida albicans TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested. Low pH increased CaTOK channel outward currents (pKa = 6.0), hyperpolarized the voltage-dependence of TOK activation, and increased pore selectivity for K+ over Na+, shifting the reversal potential (E REV) toward E K. Mutating H144 in the S1-S2 extracellular linker partially diminished pH sensitivity, suggesting H144 forms part of the CaTOK pH sensor. Functional analysis of chimeras made with pH-insensitive Saccharomyces cerevisiae TOK and point mutants revealed that CaTOK V462 and S466 in the final transmembrane segment complete the pH-responsive elements. A tripartite network of residues thus endows CaTOK with the ability to respond functionally to changes in pH.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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