Cytosolic TrkA-like RCK (regulator of K+ conductance) regulatory subunit that gates a Trk/Ktr K+ uptake channel. Q72F06 contains RCK_N and RCK_C domains and forms an octameric gating ring that docks to an inner membrane TrkH/KtrB-type pore subunit. ATP binding promotes the active/open channel state while ADP promotes an inactive/closed state. Na+ binding stabilizes the ATP-bound active conformation. The second messenger c-di-AMP can bind the RCK domain and reduce K+ uptake capacity. Critically, Q72F06 is the cytosolic REGULATOR of K+ transport, not the membrane pore itself - it does not directly transport ions but rather gates the associated membrane channel through nucleotide-dependent conformational changes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0098655 monoatomic cation transmembrane transport | IEA GO_REF:0000108 | MODIFY | Summary: This BP annotation was inferred from the MF annotation GO:0008324 (transporter activity). However, Q72F06 is the cytosolic RCK regulatory subunit, not the transmembrane pore. It regulates K+ transport rather than directly participating in it. A more appropriate annotation would be GO:1901379 (regulation of potassium ion transmembrane transport) or GO:0043266 (regulation of potassium ion transport). Reason: Q72F06 contains RCK_N and RCK_C domains characteristic of cytosolic regulatory subunits that form gating rings for Trk/Ktr channels. The deep research clearly states that DVU_0412 is "not the pore but the ligand-gated regulator controlling K+ flux through the membrane partner". The protein regulates rather than executes transport. Proposed replacements: regulation of potassium ion transmembrane transport Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Substrate of the overall system: K+; DVU_0412 itself is not the pore but the ligand-gated regulator controlling K+ flux through the membrane partner file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Heteromeric bacterial K+ importers that combine a cytosolic RCK regulatory subunit (TrkA/KtrA/KtrC) and a membrane pore-forming subunit (TrkH/KtrB/KtrD) |
| GO:0006813 potassium ion transport | IEA GO_REF:0000002 | MODIFY | Summary: This annotation was assigned via InterPro mapping of RCK_N (IPR003148) and RCK_C (IPR006037) domains. While Q72F06 is part of the K+ transport system, the InterPro-to-GO mapping does not distinguish between pore subunits that directly transport K+ and regulatory subunits that gate the channel. Q72F06 is the regulatory subunit and should be annotated to regulation of K+ transport. Reason: The RCK domains in Q72F06 form a cytosolic gating ring - they do not span the membrane or create an ion conduction pathway. The membrane-spanning TrkH/KtrB partner (not Q72F06) is the actual transporter. As stated in the deep research: "DVU_0412 itself is not the pore but the ligand-gated regulator controlling K+ flux through the membrane partner." Proposed replacements: regulation of potassium ion transport Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Architecturally, the RCK subunits form an octameric gating ring that docks to the dimeric membrane pore to control K+ flux file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Cytosolic protein assembling as an RCK ring that docks to an inner-membrane KtrB/TrkH channel |
| GO:0008324 monoatomic cation transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: This MF annotation is incorrect for Q72F06. GO:0008324 describes "enables the energy-independent facilitated diffusion" of cations across membranes - an activity performed by channels and pores. Q72F06 lacks transmembrane domains and functions as a cytosolic regulatory subunit. The appropriate MF term is GO:0015459 (potassium channel regulator activity) which describes "binds to and modulates the activity of a potassium channel." Reason: Q72F06 has RCK domains (5-121 aa RCK_N, 138-221 aa RCK_C per UniProt) but no transmembrane segments. It cannot itself transport ions across membranes. Instead, it binds ATP/ADP and undergoes conformational changes that gate the associated TrkH/KtrB membrane channel. This is a classic channel regulator function. Proposed replacements: potassium channel regulator activity Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md ATP binding to the RCK ring activates, whereas ADP-bound conformations are inactive/closed; conformational changes in the RCK ring are transmitted to gate residues in the membrane subunit file:DESVH/Q72F06/Q72F06-deep-research-falcon.md These systems act as ATP-gated channels with activity tuned by cellular signals, notably the second messenger c-di-AMP |
| GO:0005515 protein binding | IPI PMID:26873250 Bacterial Interactomes: Interacting Protein Partners Share S... | MARK AS OVER ANNOTATED | Summary: This annotation comes from an AP-MS interactome study in D. vulgaris Hildenborough. The interaction partner is Q72E47 (valS, valine-tRNA ligase) with 2 experimental observations recorded in IntAct. However, this interaction appears to be non-specific or a false positive - valS is an aminoacyl-tRNA synthetase with no known functional relationship to K+ transport regulation. The study itself notes high false positive rates in AP-MS screens. Reason: The interacting partner (valS) has no known functional connection to potassium homeostasis or channel regulation. The PMID:26873250 study is a high-throughput interactome screen, which the authors themselves note has significant false discovery rates. The "protein binding" annotation is also uninformative - if a true interaction exists with a K+ channel partner, it should be annotated more specifically. The known functional interaction of TrkA-type proteins is with TrkH/KtrB membrane pores, not aminoacyl-tRNA synthetases. Supporting Evidence: PMID:26873250 most of which are between functionally unrelated proteins. The accuracy of these networks, however, is under debate |
| GO:0015459 potassium channel regulator activity | ISS PMID:38719864 Structural basis and synergism of ATP and Na+ activation in ... | NEW | Summary: Q72F06 should be annotated with this MF term based on sequence similarity to well-characterized TrkA/KtrA proteins and conserved domain architecture. The RCK domains form gating rings that modulate K+ channel activity through ATP/ADP-dependent conformational changes. Reason: This is the core molecular function of TrkA-type proteins. Q72F06 has the characteristic RCK_N/RCK_C domain architecture and is predicted to form octameric gating rings that regulate associated K+ channels. Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md ATP binding to the RCK ring activates, whereas ADP-bound conformations are inactive/closed; conformational changes in the RCK ring are transmitted to gate residues in the membrane subunit file:DESVH/Q72F06/Q72F06-deep-research-falcon.md DVU_0412 most likely encodes a cytosolic RCK gating subunit (TrkA-like) that forms an octameric ring and associates with a cognate TrkH/KtrB-like membrane pore to mediate K+ uptake PMID:38719864 Structural basis and synergism of ATP and Na(+) activation in bacterial K(+) uptake system KtrAB. |
| GO:0005524 ATP binding | ISS PMID:38719864 Structural basis and synergism of ATP and Na+ activation in ... | NEW | Summary: TrkA/KtrA proteins bind ATP, which promotes the active/open channel state. Q72F06 has the NAD(P)-binding Rossmann-like domain (IPR036291) characteristic of nucleotide-binding RCK subunits. Reason: ATP binding is a core function of TrkA-type regulatory subunits. The NAD(P)-bd_dom_sf domain in Q72F06 is the structural basis for nucleotide binding that controls channel gating. Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md ATP binding to DVU_0412's RCK domains promotes an active, open-channel state in the associated membrane pore; ADP stabilizes a closed/inactive conformation file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Its activity is expected to be ATP/ADP-gated, further activated by Na+ PMID:38719864 Structural basis and synergism of ATP and Na(+) activation in bacterial K(+) uptake system KtrAB. |
| GO:0005737 cytoplasm | ISS PMID:38719864 Structural basis and synergism of ATP and Na+ activation in ... | NEW | Summary: TrkA-type RCK subunits are cytosolic proteins that form gating rings docking to the cytoplasmic face of membrane channel pores. Q72F06 lacks transmembrane domains. Reason: The RCK domains are cytoplasmic gating domains. The protein forms an octameric ring in the cytoplasm that docks to the inner membrane TrkH/KtrB pore. Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Cytosolic oligomeric ring apposed to the inner membrane, docking to a TrkH/KtrB pore file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Cytosolic protein assembling as an RCK ring that docks to an inner-membrane KtrB/TrkH channel PMID:38719864 Structural basis and synergism of ATP and Na(+) activation in bacterial K(+) uptake system KtrAB. |
| GO:1901379 regulation of potassium ion transmembrane transport | ISS PMID:38856222 Bacterial cell volume regulation and the importance of cycli... | NEW | Summary: The primary biological process role of Q72F06 is to regulate K+ transport through the associated Trk/Ktr channel by nucleotide-dependent gating. Reason: This BP term accurately captures the regulatory role of TrkA-type proteins in K+ transport systems. Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Cytosolic TrkA-like RCK regulatory subunit that gates a Trk/Ktr K+ uptake channel in DVH, contributing to potassium homeostasis and osmoadaptation file:DESVH/Q72F06/Q72F06-deep-research-falcon.md conformational changes in the RCK ring are transmitted to gate residues in the membrane subunit PMID:38856222 Bacterial cell volume regulation and the importance of cyclic di-AMP. |
| GO:0055075 potassium ion homeostasis | ISS PMID:38856222 Bacterial cell volume regulation and the importance of cycli... | NEW | Summary: TrkA-type proteins contribute to cellular K+ homeostasis by regulating K+ uptake in response to ATP/ADP ratios and c-di-AMP signaling. Reason: The broader physiological role of Trk/Ktr systems is maintaining intracellular K+ levels for osmoadaptation and cell volume control. Supporting Evidence: file:DESVH/Q72F06/Q72F06-deep-research-falcon.md Potassium uptake and cell volume control; functionally redundant with other K+ systems typical of bacteria, enabling stress resilience file:DESVH/Q72F06/Q72F06-deep-research-falcon.md c-di-AMP is expected to bind the RCK subunit (or other K+ transport components) and reduce K+ uptake capacity, tuning intracellular K+ and osmotic balance PMID:38856222 Bacterial cell volume regulation and the importance of cyclic di-AMP. |
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Download this section (compressed HTML)Q: What is the membrane partner (TrkH/KtrB homolog) for Q72F06 in D. vulgaris Hildenborough?
Q: Does Q72F06 bind c-di-AMP and at what affinity?
Q: What is the oligomeric state of Q72F06 (octameric as in other TrkA proteins)?
Experiment: Size exclusion chromatography to determine oligomeric state
Hypothesis: Q72F06 forms octameric RCK assemblies like other TrkA homologs
Experiment: Isothermal titration calorimetry to measure ATP, ADP, and c-di-AMP binding affinities
Hypothesis: Q72F06 binds ATP/ADP with differential affinity to regulate channel gating
Experiment: Co-purification to identify the cognate TrkH/KtrB membrane partner in D. vulgaris
Hypothesis: Q72F06 forms a stable complex with a TrkH/KtrB-type membrane pore
Experiment: Growth assays in low K+ conditions with DVU_0412 knockout strain
Hypothesis: Loss of Q72F06 impairs growth under K+-limiting conditions
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