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Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis (By similarity). Regulation of lumenal pH stability is required for autophagosome-lysosome fusion (PubMed:26317472). Also acts as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes (PubMed:26317472, PubMed:33505021). Constitutes the pore-forming subunit of the lysoK(GF) complex, a complex activated by extracellular growth factors (PubMed:33505021). The lysoK(GF) complex is composed of TMEM175 and AKT (AKT1, AKT2 or AKT3), a major target of growth factor receptors: in the complex, TMEM175 channel is opened by conformational changes by AKT, leading to its activation (PubMed:33505021). The lysoK(GF) complex is required to protect neurons against stress-induced damage (PubMed:33505021)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"H(+)(in) = H(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34979"},{"database":"ChEBI","id":"CHEBI:15378"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26317472"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33505021"}],"value":"Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons (By similarity). Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity (By similarity). Proton channel activity is directly inhibited by LAMP1 or LAMP2, facilitating lysosomal acidification (By similarity). Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state (PubMed:33505021). Activation by AKT is independent of AKT serine/threonine-protein kinase activity (PubMed:33505021)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33505021"}],"value":"Homodimer (By similarity). Interacts with AKT (AKT1, AKT2 or AKT3); leading to formation of the lysoK(GF) complex, which activates the channel (PubMed:33505021). Interacts with LAMP1; inhibiting the proton channel activity of TMEM175 (By similarity). Interacts with LAMP2; inhibiting the proton channel activity of TMEM175 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"}],"value":"Endosome membrane","id":"SL-0100"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"}],"value":"Lysosome membrane","id":"SL-0157"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9BSA9"}],"value":"Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-43 in the first module and Ile-268 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33505021"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35750034"}],"value":"Mice display accelerated loss of dopaminergic neurons and impaired motor skills (PubMed:33505021). Knockout neurons show increased damage in response to insults and an accumulation of alpha-synuclein (PubMed:33505021, PubMed:35750034). 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