KdpC is a periplasmic, single-pass membrane subunit of the KdpFABC high-affinity potassium-transporting ATPase complex. It functions as a catalytic chaperone that increases the ATP-binding affinity of the ATPase subunit KdpB by forming a transient KdpB/KdpC/ATP ternary complex. KdpC does not itself possess catalytic ATPase or hydrolase activity; rather, it modulates ion access in the periplasmic vestibule and stabilizes complex assembly. The KdpFABC complex is induced under potassium limitation to enable high-affinity K+ uptake (Stock et al., 2023).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0071805 potassium ion transmembrane transport | IEA GO_REF:0000118 | ACCEPT | Summary: KdpC is part of the KdpFABC complex which transports potassium ions across the membrane. While KdpC does not directly catalyze ion transport (this is performed by KdpA/KdpB), it is an essential accessory subunit required for complex function. The annotation correctly reflects KdpC's involvement in the biological process. Reason: KdpC is an essential subunit of the KdpFABC potassium-transporting ATPase. Contemporary structural and mechanistic studies confirm that KdpC is required for proper complex function, even though it does not directly catalyze transport. The 'involved_in' qualifier is appropriate for an accessory subunit that enables the process through its catalytic chaperone function. Supporting Evidence: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md KdpC subunit role/definition: KdpC is periplasmically oriented and single-pass. Contemporary models assign KdpC a non-catalytic but essential structural/modulatory role |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | REMOVE | Summary: This annotation is based on UniProtKB keyword mapping (KW-0547). The annotation is misleading for KdpC. While KdpC participates in forming a transient ternary complex with KdpB and ATP, it is KdpB that directly binds ATP. KdpC functions as a catalytic chaperone to increase ATP-binding affinity of KdpB, but does not itself possess intrinsic nucleotide-binding capability. Reason: KdpC does not directly bind nucleotides. The UniProt HAMAP annotation states that KdpC "increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex." This describes an indirect role in modulating ATP binding to KdpB, not direct nucleotide binding by KdpC itself. The cryo-EM structures show ADP and Mg2+ bound in the KdpB N-domain, not KdpC. This is an over-annotation resulting from keyword propagation that does not accurately reflect KdpC's molecular function. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | REMOVE | Summary: This annotation derives from UniRule:UR000058586 and keyword mapping. Like the nucleotide binding annotation, this is an over-annotation. KdpC participates in ternary complex formation with KdpB and ATP, but does not itself directly bind ATP. The ATP-binding site resides in KdpB, not KdpC. Reason: KdpC is not an ATP-binding protein. The catalytic aspartate (D307) that becomes phosphorylated during the reaction cycle is located in KdpB, and ATP/ADP are bound to the KdpB N-domain. KdpC's role is to enhance ATP-binding affinity of KdpB through allosteric/chaperone mechanisms, not to directly bind ATP. This annotation incorrectly attributes to KdpC a molecular function that belongs to KdpB. Supporting Evidence: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md KdpB is the P-type ATPase motor file:DESVH/Q725T8/Q725T8-deep-research-falcon.md D307 phosphorylated and ADP + two Mg2+ bound in the N-domain |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: KdpC is localized to the bacterial inner membrane (equivalent to plasma membrane) as a single-pass membrane protein with periplasmic orientation. This annotation is correct and well-supported. Reason: Multiple sources confirm KdpC is a membrane protein. UniProt HAMAP annotation states "Cell inner membrane; Single-pass membrane protein." Structural studies confirm KdpC is periplasmically oriented and embedded in the cytoplasmic membrane. For bacteria, the inner/cytoplasmic membrane corresponds to GO:0005886 plasma membrane. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt Cell inner membrane file:DESVH/Q725T8/Q725T8-deep-research-falcon.md Periplasmically oriented, single-pass membrane protein embedded with KdpA/KdpB/KdpF in the cytoplasmic membrane |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation is too general. KdpC is specifically involved in potassium ion transport as part of the KdpFABC complex. The more specific term GO:0006813 (potassium ion transport) is already annotated. Reason: While technically correct (potassium is a monoatomic ion), this annotation adds no information beyond what GO:0006813 (potassium ion transport) and GO:0071805 (potassium ion transmembrane transport) already provide. The KdpFABC complex is specifically a potassium transporter, not a general ion transporter. Retaining this broader term alongside the specific terms is redundant. However, this is not incorrect per se - just uninformative. Supporting Evidence: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump induced under K+ limitation/osmotic stress |
| GO:0006813 potassium ion transport | IEA GO_REF:0000120 | ACCEPT | Summary: KdpC is an essential subunit of the KdpFABC high-affinity potassium transport system. This biological process annotation is appropriate. Reason: KdpC is required for proper function of the KdpFABC complex, which mediates high-affinity K+ uptake. The annotation correctly captures KdpC's involvement in the biological process of potassium ion transport. However, GO:0071805 (potassium ion transmembrane transport) is more specific and also present, so this annotation is somewhat redundant but not incorrect. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt Part of the high-affinity ATP-driven potassium transport (or Kdp) system file:DESVH/Q725T8/Q725T8-deep-research-falcon.md KdpFABC mediates high-affinity K+ uptake under limitation |
| GO:0008556 P-type potassium transmembrane transporter activity | IEA GO_REF:0000120 | MODIFY | Summary: This molecular function annotation is inappropriate for KdpC. GO:0008556 describes the enzymatic transporter activity, which in the KdpFABC complex is performed by KdpB (the P-type ATPase) together with KdpA (the K+ channel). KdpC does not possess transporter activity; it is an accessory subunit with a regulatory/chaperone role. Reason: GO:0008556 is defined as "Enables the transfer of a solute... according to the reaction: ATP + H2O + K+(out) = ADP + phosphate + K+(in)." This describes catalytic activity that KdpC does not possess. KdpB is the ATPase that hydrolyzes ATP (containing the catalytic aspartate D307), and KdpA is the K+ translocase. KdpC functions as a "catalytic chaperone" that modulates KdpB activity but does not itself catalyze transport. This annotation incorrectly attributes complex activity to an individual subunit that lacks the catalytic machinery. Proposed replacements: ATPase activator activity Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB file:DESVH/Q725T8/Q725T8-deep-research-falcon.md KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: This general membrane annotation is correct but redundant given the more specific GO:0005886 (plasma membrane) annotation already present. Reason: KdpC is indeed a membrane protein, so this annotation is not incorrect. However, GO:0005886 (plasma membrane) is more specific and accurately describes KdpC's localization. This broader term adds no additional information. It derives from InterPro domain IPR003820 which appropriately associates KdpC with membranes. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt Single-pass membrane protein |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | REMOVE | Summary: This annotation is incorrect for KdpC. The hydrolase (ATPase) activity in the KdpFABC complex resides in KdpB, not KdpC. KdpC does not possess catalytic hydrolase activity. Reason: The ATPase activity (ATP hydrolysis) is carried out by KdpB, which contains the catalytic aspartate D307 that becomes phosphorylated during the P-type ATPase cycle. KdpC has no catalytic residues and functions as a regulatory/ chaperone subunit. The UniProtKB keyword "Hydrolase" (KW-0378) was incorrectly propagated to KdpC, likely because the KdpFABC complex has hydrolase activity. This conflates complex function with individual subunit function. KdpC "acts as a catalytic chaperone" but is not itself a catalyst. Supporting Evidence: file:DESVH/Q725T8/Q725T8-deep-research-falcon.md catalytic aspartate D307 cycles through phosphorylation file:DESVH/Q725T8/Q725T8-uniprot.txt This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB |
| GO:0031004 potassium ion-transporting ATPase complex | ISS GO_REF:0000024 | NEW | Summary: KdpC is part of the KdpFABC potassium ion-transporting ATPase complex. GO:0031004 specifically describes this complex in E. coli, noting that "KdpC and KdpF seem to be involved in assembly and stabilization of the complex." Reason: This cellular component term precisely describes KdpC's localization as part of a defined protein complex. The GO term definition explicitly mentions KdpC: "The E. coli complex consists of 4 proteins: KdpA is the potassium ion translocase, KdpB is the ATPase, and KdpC and KdpF seem to be involved in assembly and stabilization of the complex." This is more informative than the generic membrane terms currently annotated. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt The system is composed of three essential subunits: KdpA, KdpB and KdpC file:DESVH/Q725T8/Q725T8-deep-research-falcon.md The KdpFABC complex: a heterotetrameric, ATP-dependent K+ pump |
| GO:0001671 ATPase activator activity | ISS GO_REF:0000024 | NEW | Summary: KdpC functions as a catalytic chaperone that increases ATP-binding affinity and promotes ATPase activity of KdpB. GO:0001671 ("Binds to and increases the activity of an ATP hydrolysis activity") accurately describes this molecular function. Reason: This molecular function term accurately captures KdpC's primary role in the KdpFABC complex. Unlike the incorrect annotations of ATP binding or hydrolase activity, this term describes KdpC's actual regulatory function of enhancing KdpB's ATPase activity through formation of a transient ternary complex. This is supported by UniProt HAMAP annotation and contemporary structural studies. Supporting Evidence: file:DESVH/Q725T8/Q725T8-uniprot.txt This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex file:DESVH/Q725T8/Q725T8-deep-research-falcon.md KdpC is not the catalytic ATPase; rather, it is a periplasmic single-spanning subunit thought to modulate ion access in the periplasmic vestibule and help stabilize the KdpA–KdpB interface |
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Download this section (compressed HTML)Q: Does KdpC directly contact ATP in the ternary complex, or does it act purely through allosteric effects on KdpB?
Q: Is there structural data specific to D. vulgaris KdpFABC that would confirm conservation of KdpC's role?
Experiment: Cryo-EM structure of KdpFABC with focus on KdpC-ATP proximity to determine if KdpC directly contacts ATP in the ternary complex.
Hypothesis: KdpC may directly contact ATP to facilitate its binding to KdpB
Experiment: KdpC mutagenesis affecting KdpB ATPase activity to identify KdpC residues critical for its catalytic chaperone function.
Hypothesis: Specific KdpC residues at the KdpB interface are required for ATPase activation
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