khtT

UniProt ID: O07535
Organism: Bacillus subtilis subsp. subtilis str. 168
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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.
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.
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.

Core Functions

Bind cyclic di-AMP through the RCK_C domain to sense the messenger at the KhtTU antiporter.

Molecular Function:
cyclic-di-AMP binding
Cellular Locations:
Supporting Evidence:
  • PMID:33790011
    We have confirmed c-di-AMP binding to KhtT and determined the crystal structure of this complex.

Regulate potassium export by binding KhtU: the apo subunit restrains transport and c-di-AMP binding relieves restraint.

Cellular Locations:
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.

References

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Notes

(khtT-notes.md)

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