KhtT is the cytosolic regulatory subunit of the Bacillus subtilis KhtTU potassium/proton antiporter. Its RCK_C domain binds cyclic di-AMP. Apo-KhtT restrains KhtU-mediated potassium export, whereas cyclic di-AMP binding relieves this restraint; alkaline pH increases the sensitivity of the complex to the messenger. KhtU supplies the membrane transport pathway and can transport without KhtT.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: KhtT acts at the cytoplasmic face of the plasma membrane in association with the membrane antiporter KhtU. Reason: The PAINT PTN002019571 assertion of a membrane-associated transporter component is consistent with the target-specific KhtTU architecture and curated peripheral-membrane location; it does not imply that KhtT spans the bilayer. The required current PAINT lineage query completed on 2026-11-04 and found no IRD or IKR loss on this lineage. Target-specific localization and complex evidence independently support the retained biological claim. Supporting Evidence: PMID:33790011 a K+/H+ antiporter composed of the membrane protein KhtU and the cytosolic protein KhtT. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: KhtT acts at the cytoplasmic face of the plasma membrane in association with the membrane antiporter KhtU. Reason: The UniProt cell-membrane mapping describes a peripheral regulatory subunit bound to KhtU, consistent with the characterized complex. Cytosolic topology is compatible with this functional membrane association. Supporting Evidence: PMID:33790011 a K+/H+ antiporter composed of the membrane protein KhtU and the cytosolic protein KhtT. |
| GO:0006813 potassium ion transport | IEA GO_REF:0000002 | MODIFY | Summary: KhtT controls potassium export through its interaction with KhtU. Reason: The experimentally executed role is regulation of potassium transport: apo-KhtT slows KhtU and ligand binding relieves the brake. Refine the process to that regulatory role without assigning the membrane transport step to the cytosolic subunit. The sign is conditional on ligand state, so a sign-neutral regulatory term is appropriate. Proposed replacements: regulation of potassium ion transport Supporting Evidence: PMID:33790011 indicating that KhtT inhibits the function of KhtU, in accordance with our in vitro data and previous findings PMID:33790011 demonstrating that c-di-AMP activates KhtTU and that pH increases its sensitivity to this nucleotide. |
| GO:0008324 monoatomic cation transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: KhtT regulates the membrane transporter KhtU rather than independently transporting cations. Reason: The RCK domain belongs to a cytosolic regulatory subunit. Reconstitution in PMID:33790011 shows that KhtU alone transports potassium and that adding KhtT restrains that activity; c-di-AMP relieves restraint. The specific supported molecular role is transporter regulation. This is a correction of the role, not a descendant refinement of transport chemistry. Proposed replacements: transporter regulator activity Supporting Evidence: PMID:33790011 indicating that KhtT inhibits the function of KhtU, in accordance with our in vitro data and previous findings PMID:33790011 a K+/H+ antiporter composed of the membrane protein KhtU and the cytosolic protein KhtT. |
| GO:0098655 monoatomic cation transmembrane transport | IEA GO_REF:0000108 | MODIFY | Summary: KhtT controls potassium export through its interaction with KhtU. Reason: The experimentally executed role is regulation of potassium transport: apo-KhtT slows KhtU and ligand binding relieves the brake. Refine the process to that regulatory role without assigning the membrane transport step to the cytosolic subunit. The sign is conditional on ligand state, so a sign-neutral regulatory term is appropriate. Proposed replacements: regulation of potassium ion transport Supporting Evidence: PMID:33790011 indicating that KhtT inhibits the function of KhtU, in accordance with our in vitro data and previous findings PMID:33790011 demonstrating that c-di-AMP activates KhtTU and that pH increases its sensitivity to this nucleotide. |
| GO:0180001 cyclic-di-AMP binding | IDA PMID:33790011 c-di-AMP, a likely master regulator of bacterial K(+) homeos... | NEW | Summary: Bind cyclic di-AMP through the RCK_C domain to sense the messenger at the KhtTU antiporter. Reason: Direct biochemical and structural assays establish c-di-AMP binding by this gene product. The activity is absent from the seed annotation rows, and is neither an ancestor nor a descendant of another proposed activity. This adds a demonstrated molecular function, not an inference from a downstream phenotype. Supporting Evidence: PMID:33790011 We have confirmed c-di-AMP binding to KhtT and determined the crystal structure of this complex. |
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