KCTD14 encodes a BTB/POZ domain-containing protein that is a member of the KCTD (potassium channel tetramerization domain-containing) protein family. The protein contains a T1-type BTB domain (residues 33-130) that is predicted to mediate pentameric homooligomerization based on family-wide structural analysis. Unlike many other KCTD family members, recent AlphaFold-based structural modeling (2024) suggests KCTD14 does NOT form a stable complex with Cullin3 (Cul3), indicating it may not function as a canonical CRL3 E3 ubiquitin ligase adaptor. The protein's primary molecular function remains poorly characterized, though high-throughput interaction studies have detected associations with STK16, TCF4, and ACSF3. KCTD14 shows low tissue specificity and has been detected in parotid gland and 138 other cell types or tissues.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0051260 protein homooligomerization | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: This annotation is inferred from InterPro domain analysis. The T1-type BTB domain (IPR003131) in KCTD14 is structurally homologous to domains that mediate oligomerization in other KCTD family members. AlphaFold-based structural surveys support that KCTD BTB domains frequently assemble into pentamers, and KCTD14 is expected to oligomerize via its BTB domain in keeping with the family trend (Balasco et al. 2024). Reason: The annotation is well-supported by structural homology. The BTB/POZ domain is a well-characterized oligomerization domain. Family-wide AlphaFold analyses confirm that KCTD proteins typically form pentameric assemblies via their BTB domains. However, OpenScientist analysis argues this is best treated as a non-core assembly property that enables an unknown downstream molecular function, rather than the endpoint core function of KCTD14. Supporting Evidence: file:human/KCTD14/KCTD14-deep-research-falcon.md KCTD14 is expected to oligomerize via its BTB domain, most commonly as a homopentamer, in keeping with the family trend file:human/KCTD14/KCTD14-hypotheses/core-function-1-go-0042802/openscientist.md Self-binding is a structural prerequisite shared across the entire KCTD family that enables downstream molecular activities (Cullin3 adaptor function, GΞ²Ξ³ modulation, receptor scaffolding), which are the true core functions for characterized family members. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This annotation derives from the Rolland et al. 2014 proteome-scale human interactome map, which used yeast two-hybrid screening to identify approximately 14,000 high-quality binary protein-protein interactions. This is a high-throughput study without specific KCTD14-focused validation. Reason: Per curation guidelines, GO:0005515 (protein binding) is uninformative and should be avoided. The term does not convey any specific information about the molecular function of KCTD14. The high-throughput nature of the study means specific interactors were not validated for KCTD14 individually. If specific binding partners were identified, more informative molecular function terms should be used instead. The interaction data itself may be useful but the GO:0005515 annotation is not informative. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: This annotation derives from the BioPlex 2.0 study (Huttlin et al. 2017), which used affinity-purification mass spectrometry (AP-MS) to identify protein-protein interactions for over 25% of human protein-coding genes. BioPlex 2.0 contains over 56,000 candidate interactions. This is a high-throughput proteome-scale study. Reason: Per curation guidelines, GO:0005515 (protein binding) is uninformative and should be avoided. While BioPlex 2.0 is a valuable resource for identifying potential interaction partners, the generic protein binding annotation does not convey specific functional information about KCTD14. The underlying interaction data may be valuable for characterizing KCTD14 function, but the GO annotation itself is not informative. Supporting Evidence: PMID:28514442 BioPlex 2.0 is the largest collection of human co-complex data assembled from a single pipeline to date, containing 56,553 interactions from 10,961 proteins |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: This annotation derives from Chen et al. 2018, which established an interactome perturbation framework to prioritize damaging missense mutations for developmental disorders. The study analyzed approximately 2,000 de novo missense mutations in the context of the human interactome network. This is a computational/high-throughput study focused on mutation effects on interactions rather than direct functional characterization. Reason: Per curation guidelines, GO:0005515 (protein binding) is uninformative and should be avoided. This study was focused on identifying disease-relevant missense mutations by their effects on protein interactions, not on characterizing the specific molecular functions of individual proteins like KCTD14. The generic protein binding annotation provides no insight into KCTD14's specific function. Supporting Evidence: PMID:29892012 Here we establish an experimentally and computationally integrated approach to investigate the functional impact of missense mutations in the context of the human interactome network |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This annotation derives from the BioPlex 3.0/dual network study (Huttlin et al. 2021), which profiled protein interactions in both 293T and HCT116 cells using affinity-purification mass spectrometry. BioPlex 3.0 includes 118,162 interactions among 14,586 proteins. This is a high-throughput proteome-scale study. Reason: Per curation guidelines, GO:0005515 (protein binding) is uninformative and should be avoided. While this dual-network approach provides valuable context about cell-type-specific interactions, the generic protein binding annotation does not convey any specific information about KCTD14's molecular function. If specific binding partners were validated, more informative terms should be used. Supporting Evidence: PMID:33961781 BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins |
| GO:0042802 identical protein binding | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: GO:0042802 is a more specific annotation lead for the KCTD14 self-interaction detected by yeast two-hybrid, but OpenScientist analysis recommends treating it as a non-core assembly property rather than a core molecular function. Supporting Evidence: file:human/KCTD14/KCTD14-deep-research-falcon.md KCTD14 is expected to oligomerize via its BTB domain, most commonly as a homopentamer, in keeping with the family trend file:human/KCTD14/KCTD14-hypotheses/core-function-1-go-0042802/openscientist.md GO:0042802 could be validly assigned based on the Y2H self-interaction from [PMID: 25416956](https://pubmed.ncbi.nlm.nih.gov/25416956/), using IPI evidence code. |
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Download this section (compressed HTML)Q: What are the specific binding partners of KCTD14 and what biological processes do these interactions serve?
Q: Does KCTD14 have any scaffolding or regulatory functions independent of Cullin3?
Q: What is the subcellular localization of KCTD14 in different cell types?
Q: Does KCTD14 interact with STK16 and TCF4 in vivo and what are the functional consequences of these interactions?
Experiment: Co-immunoprecipitation or proximity labeling (BioID/APEX) to identify and validate specific interaction partners
Experiment: Immunofluorescence or subcellular fractionation to determine cellular localization
Experiment: CRISPR knockout or knockdown studies to identify phenotypic consequences
Experiment: Biochemical characterization of oligomeric state using size exclusion chromatography or native PAGE
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