DVU_0413

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0098655 monoatomic cation transmembrane transport	IEA GO_REF:0000108	MODIFY	Summary: This annotation is correct but overly general. TrkH-family proteins are specifically potassium ion channels, not general cation transporters. The term was inferred from the MF annotation GO:0008324 (monoatomic cation transmembrane transporter activity). Reason: DVU_0413 is a TrkH-family K+ uptake pore subunit with well-characterized specificity for potassium ions. Structural studies of homologous KtrAB complexes demonstrate K+ selectivity through a selectivity filter (Chiang et al. 2024). The term should be made more specific to potassium ion transmembrane transport. Proposed replacements: potassium ion transmembrane transport Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md KtrAB-type complexes are gated by RCK octameric rings (KtrA/TrkA); ATP binding (vs ADP) adopts an activating conformation file:DESVH/Q72F05/Q72F05-deep-research-falcon.md Trk/Ktr systems: Bacterial low-affinity K+ uptake assemblies composed of a membrane pore subunit (TrkH/KtrB/KtrD) and a cytosolic regulatory ring
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct cellular component annotation. TrkH/KtrB homologs are integral inner-membrane proteins forming the K+ conductance pathway. In bacteria, the plasma membrane is equivalent to the inner/cytoplasmic membrane where this protein localizes. Reason: The TrkH domain architecture and transmembrane nature support inner-membrane (plasma membrane) localization. This is consistent with the established function of TrkH-family proteins as membrane-embedded K+ channels (Foster et al. 2024). Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md TrkH/KtrB homologs are integral inner-membrane proteins forming the K+ conductance pathway
GO:0006811 monoatomic ion transport	IEA GO_REF:0000043	MODIFY	Summary: This is a very general parent term that is technically correct but uninformative. The annotation comes from UniProtKB keyword mapping. Given that DVU_0413 specifically transports potassium ions, more specific terms are warranted. Reason: This general term does not capture the specific substrate (K+) of the TrkH-family transporter. While not incorrect, it should be replaced with the more specific potassium ion transport term for informative annotation. Proposed replacements: potassium ion transport Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md TrkH/KtrB-family pores are selective for K+ and operate as low-affinity, membrane-potential-driven channels
GO:0006812 monoatomic cation transport	IEA GO_REF:0000002	MODIFY	Summary: Derived from InterPro:IPR003445 (Cat_transpt domain). This is a correct but overly broad annotation that encompasses all cation transport. TrkH proteins are specifically K+ selective. Reason: The Cat_transpt domain (IPR003445) is found in cation transporters, but TrkH-family proteins have evolved specificity for K+. Structural and biochemical evidence from homologous systems confirms K+ selectivity, warranting a more specific term. Proposed replacements: potassium ion transport Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB
GO:0008324 monoatomic cation transmembrane transporter activity	IEA GO_REF:0000002	MODIFY	Summary: This molecular function annotation from InterPro is correct but should be made more specific. DVU_0413 has potassium ion transmembrane transporter activity, not general cation transporter activity. Reason: TrkH-family proteins function specifically as K+ channels. The protein enables transfer of K+ ions across the membrane through a selectivity filter, with activity regulated by the RCK domain of the cognate TrkA partner. A more specific MF term better captures the actual molecular function. Proposed replacements: potassium ion transmembrane transporter activity Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md High-resolution cryo-EM structures of Bacillus subtilis KtrAB demonstrate that ATP binding to the KtrA octamer stabilizes an active conformation that enhances K+ flux through KtrB file:DESVH/Q72F05/Q72F05-deep-research-falcon.md The membrane subunit (e.g., TrkH/KtrB) provides the ion-conducting pathway
GO:0030001 metal ion transport	IEA GO_REF:0000117	REMOVE	Summary: This ARBA-derived annotation is problematic. While potassium is technically a metal (alkali metal), in GO ontology conventions, "metal ion transport" (GO:0030001) is typically used for transition metals and heavy metals (Fe, Zn, Cu, etc.), not for alkali metal cations like K+ and Na+. Potassium ion transport has its own dedicated branch (GO:0006813). Reason: This annotation represents a mapping error or overly broad inference. In GO usage and biological convention, K+ is classified under "monoatomic cation" and "potassium ion" terms rather than "metal ion" terms. The term GO:0030001 is a sibling of GO:0006812 (monoatomic cation transport), not a parent, and is typically reserved for transition/heavy metals. Retaining this annotation would be misleading about the substrate specificity of DVU_0413. Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md Trk/Ktr systems: Bacterial low-affinity K+ uptake assemblies composed of a membrane pore subunit (TrkH/KtrB/KtrD)
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: This is the most general transmembrane transport term. While technically correct (DVU_0413 does perform transmembrane transport), it provides minimal information about the actual function. Reason: This very general term is implied by more specific annotations. It is not incorrect, but adds no functional insight beyond what is captured by potassium-specific terms. Keeping as non-core maintains the hierarchical relationship without cluttering the core annotation set. Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md The membrane subunit (e.g., TrkH/KtrB) provides the ion-conducting pathway
GO:1990573 potassium ion import across plasma membrane	ISS file:DESVH/Q72F05/Q72F05-deep-research-falcon.md	NEW	Summary: TrkH/Ktr systems function specifically in K+ uptake (import) rather than export. This term captures the directionality of transport that is missing from the existing annotations. Reason: DVU_0413 is part of the Trk K+ uptake system, which specifically imports K+ into the cell. The deep research clearly indicates this is an uptake/import system operating when external K+ is in the mM range. This term more precisely describes the biological process than the bidirectional "transport" terms. Supporting Evidence: file:DESVH/Q72F05/Q72F05-deep-research-falcon.md Trk/Ktr systems are generally ATP-gated channels that exploit the membrane potential for inward K+ flux when extracellular K+ is relatively high (mM range) file:DESVH/Q72F05/Q72F05-deep-research-falcon.md Trk-type K+ transporter ranked as the top genomic feature linked to high salinity, highlighting the ecological importance of TrkH-mediated salt-in strategies