Cullin-3 is the central scaffold of CRL3 ubiquitin ligase complexes. Its N-terminal region recruits BTB/POZ-containing substrate adaptors, while its C-terminal region engages RBX1 and the ubiquitin-transfer machinery. These assemblies control protein abundance through ubiquitin-dependent proteasomal turnover and also generate non-degradative ubiquitin signals that regulate mitosis, membrane trafficking and other substrate-specific processes. CUL3 acts in nuclear and cytoplasmic compartments, with regulated Golgi, membrane and mitotic pools. Adaptor choice couples the same scaffold to targets involved in oxidative-stress responses, cell-cycle control, receptor and metabolic signaling, and transcriptional regulation. The displayed 768-residue product and two shorter splice products differ in the N-terminal adaptor-binding region: the 744-residue product lacks residues 1–24 and the 702-residue product lacks residues 23–88 of the displayed sequence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Reason: Actual current PTHR11932 topology and target sequence place human CUL3 below the nuclear-localization IBD, with no target-path loss. This is consistent with independently measured nuclear/nucleoplasmic CUL3 pools. The target occurring among descendant evidence is legitimate grounding, not circularity. Supporting Evidence: GO_REF:0000033 |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Reason: The actual PAINT node lies on the CUL3 lineage, with experimental descendant evidence and no target-specific loss. Human CUL3 supplies the scaffold for substrate ubiquitination and consequent proteasomal turnover in multiple reconstituted and cellular CRL3 systems; this is performed participation, not merely being a degradation substrate. Supporting Evidence: GO_REF:0000033 |
| GO:0160072 ubiquitin ligase complex scaffold activity | IBA GO_REF:0000033 | ACCEPT | Reason: The genuine target-path IBD agrees with CUL3 sequence architecture and primary complex-assembly experiments: CUL3 links BTB substrate adaptors to the RBX1/E2 module. Preserve the specific scaffold activity, including legitimate target-derived descendant evidence. Supporting Evidence: GO_REF:0000033 |
| GO:0016567 protein ubiquitination | IBA GO_REF:0000033 | ACCEPT | Reason: The current IBD is inherited on the actual CUL3 path. CUL3 structurally participates in ubiquitination by joining substrate-recognition and catalytic modules; the process assertion does not require CUL3 itself to form the catalytic ubiquitin intermediate. Supporting Evidence: GO_REF:0000033 |
| GO:0031625 ubiquitin protein ligase binding | IBA GO_REF:0000033 | ACCEPT | Reason: The target-path IBD supports binding to ubiquitin ligase machinery, including the experimentally established RBX1 interaction. This binding claim is not an assertion that CUL3 is an autonomous enzyme. Preserve the valid source term alongside the more informative scaffold core. Supporting Evidence: GO_REF:0000033 |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Reason: The actual target-path PAINT assertion and repeated human assembly/reconstitution experiments identify CUL3 as the defining scaffold of CRL3. There is no biological basis to reject the placement merely because some current donor sets differ from the historical snapshot. Supporting Evidence: GO_REF:0000033 |
| GO:0000209 protein polyubiquitination | IEA GO_REF:0000117 | ACCEPT | Reason: The matched human ARBA branch is compatible with directly measured CRL3-dependent polyubiquitination. CUL3 supplies the scaffold for the reaction; substrate-specific chain linkage and degradative outcome require their own evidence. Supporting Evidence: GO_REF:0000117 |
| GO:0000278 mitotic cell cycle | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The matched ARBA assertion is broad but biologically supported by CUL3-dependent mitotic Aurora and spindle/cytokinesis mechanisms in PMID:17543862, PMID:19995937, PMID:23213400 and PMID:19261606. Retain this cellular context rather than treating all mitotic participation as an indirect disease phenotype. Supporting Evidence: GO_REF:0000117 |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The UniProt-location mapping is corroborated by actual CUL3 spindle-pole localization in PMID:23213400. This is a real cell-cycle-dependent pool, not the universal location of every CUL3 complex. Supporting Evidence: GO_REF:0000044 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Reason: The composite source includes experimentally supported mouse localization and UniProt nuclear annotation; independent human nuclear observations and HPA nucleoplasm staining corroborate the conserved nuclear pool. Preserve the broad nucleus assertion without restricting all CUL3 to the nucleus. Supporting Evidence: GO_REF:0000120 |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Reason: Mouse donor and UniProt cytoplasmic localization are consistent with human CUL3 cytoplasmic complexes and imaging. The broad compartment is valid and is not replaced merely because some source-specific annotations resolve cytosol. Supporting Evidence: GO_REF:0000120 |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | KEEP AS NON CORE | Reason: The source maps a genuine Golgi-associated pool. Human CUL3–RHOBTB3 localization and cyclin-E turnover at the Golgi in PMID:24145166 independently support this context; it does not imply a transmembrane CUL3 protein. Supporting Evidence: GO_REF:0000120 |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The location mapping is compatible with the human centrosomal CUL3 signal in PMID:23213400. Retain a context-dependent localization, distinct from evidence for the scaffold activity performed there. Supporting Evidence: GO_REF:0000044 |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: CUL3 has measured mitotic-spindle localization, including the primary Aurora-regulatory studies. Preserve this non-core localization instead of requiring the scaffold to be confined to diffuse cytosol or nucleus. Supporting Evidence: GO_REF:0000044 |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000002 | ACCEPT | Reason: The InterPro-to-GO mapping describes the ubiquitin-dependent catabolic process, which CUL3 performs structurally within CRL3. The source does not require autonomous catalytic ubiquitin transfer by the scaffold. Supporting Evidence: GO_REF:0000002 |
| GO:0006915 apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The matched ARBA branch is broad, but CUL3-dependent ubiquitination participates in specific apoptotic signaling contexts, including the caspase-8 system in PMID:19427028. Retain apoptosis as a contextual output rather than the defining molecular activity of CUL3. Supporting Evidence: GO_REF:0000117 |
| GO:0006950 response to stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The matched rule is compatible with direct CUL3-complex participation in oxidative-stress and other regulated substrate responses. The general response-to-stress process is retained as a broad context, with no claim that all stress pathways use CUL3. Supporting Evidence: GO_REF:0000117 |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: CUL3-dependent ubiquitination controls specific signaling intermediates, including Notch, NRF2 and Rho regulators. The current rule matches the target, and the broad signaling assertion is biologically valid, although less informative than the source-specific mechanisms. Supporting Evidence: GO_REF:0000117 |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: CUL3 regulates gene output through turnover of transcription regulators and, in the ARMC5 system, RNA polymerase II machinery. This supports regulation of gene expression as a context-dependent consequence of performed ubiquitination, without making CUL3 a DNA-binding transcription factor. Supporting Evidence: GO_REF:0000117 |
| GO:0031461 cullin-RING ubiquitin ligase complex | IEA GO_REF:0000120 | MODIFY | Reason: The InterPro/UniProt mapping correctly identifies a cullin-RING complex, while the human gene and direct complex-assembly evidence establish the more specific Cul3-RING ubiquitin ligase complex. Refine the broad valid CC term without rewriting its machine source. Proposed replacements: Cul3-RING ubiquitin ligase complex Supporting Evidence: GO_REF:0000120 |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The source derives from the UniProt ciliary-location annotation. PMID:28395323 explicitly studies CUL3 as well as DCDC2C and reports experimental sperm-flagellar expression patterns; the annotation is not rejected as a paralog mix-up from its title. Retain the context-dependent flagellar pool with curator deference, without claiming constitutive ciliary localization. Supporting Evidence: GO_REF:0000044 |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000002 | ACCEPT | Reason: The InterPro mapping supports a cullin region associated with ubiquitin-ligase binding, and direct RBX1 association corroborates this. Binding to the catalytic subunit and serving as the scaffold are compatible activities; the source is not an autonomous-catalysis assertion. Supporting Evidence: GO_REF:0000002 |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000117 | ACCEPT | Reason: The matched ARBA branch agrees with numerous independently demonstrated CRL3-dependent proteasomal degradation mechanisms. The scaffold performs a structural step of substrate ubiquitination, which justifies process participation. Supporting Evidence: GO_REF:0000117 |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Reason: The GO_REF:0000108 inference broadens the recorded postsynaptic catabolic context to postsynapse. The CUL3–actinfilin–GluR6 evidence provides a plausible and curated neuronal complex context; retain it as non-core and do not claim new high-resolution human localization. Supporting Evidence: GO_REF:0000108 |
| GO:0005515 protein binding | IPI PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | KEEP AS NON CORE | Reason: PMID:12609982 is represented by two positive CUL3–CAND1 affinity/co-immunoprecipitation records. CAND1 is an exchange regulator, not a CUL3 substrate adaptor by that fact alone. Retain the measured association without inventing a separate catalytic or adaptor activity for CUL3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... | KEEP AS NON CORE | Reason: The source concerns CUL3 complexes containing RBX1 and several BTB proteins. The direct mitotic studies support functional CUL3 complexes, but this combined partner assertion is broader than any single domain-binding class. The present interaction export has no literal matching records for this older paper; independent source evidence supports the association, not a new class for every partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18775313 UBXD7 binds multiple ubiquitin ligases and implicates p97 in... | KEEP AS NON CORE | Reason: Four literal anti-tag co-immunoprecipitation records support the CUL3–UBXN7 association in PMID:18775313. UBXN7 recruits ubiquitinated material and p97 machinery; association does not make CUL3 an unfoldase or an enzyme-substrate adaptor. Preserve this positive generic assertion as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18850735 Characterization of the human COP9 signalosome complex using... | MODIFY | Reason: The exact tandem-affinity record identifies COPS5/JAB1, the catalytic deneddylating subunit of COP9 signalosome, as the partner. Enzyme binding describes this positive association more informatively than unrestricted protein binding; it does not assign deneddylase activity to CUL3 or prove an isolated binary interface. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | KEEP AS NON CORE | Reason: Eight literal records support association with TRAIL/TNFSF10 and caspase-8 in the death-receptor signaling context of PMID:19427028. This mixed ligand/protease assertion cannot be uniformly narrowed to protease binding, and does not mean CUL3 itself is a death-receptor ligand or caspase. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | MODIFY | Reason: The positive anti-tag co-immunoprecipitation record is specifically with COPS5, an enzymatic COP9 signalosome subunit. Refine the partner class to enzyme binding while retaining complex-association scope; the experiment does not transfer COPS5 deneddylase activity to CUL3. Proposed replacements: enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19617556 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation ... | KEEP AS NON CORE | Reason: Actual PMID:19617556 experiments support CUL3 association with DCUN1D3/DCNL3 and DCNL3-dependent membrane recruitment/neddylation. DCNL3 is a neddylation cofactor; retain the measured interaction without treating CUL3 as the NEDD8-transfer enzyme. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... | MODIFY | Reason: The actual PMID:20389280 Results and binding-defective KLHL20 constructs place CUL3 recruitment through the KLHL20 BTB region. POZ/BTB domain binding therefore captures the measured recognition more specifically than generic association; the DAPK ubiquitination is the output of the assembled CUL3–ROC1–KLHL20 complex. Proposed replacements: POZ domain binding Supporting Evidence: PMID:20389280 KLHL20 binds DAPK and Cullin 3 (Cul3) via its Kelch-repeat domain and BTB domain, respectively. |
| GO:0005515 protein binding | IPI PMID:20554658 Kelch-like homologue 9 mutation is associated with an early ... | MODIFY | Reason: PMID:20554658 compares wild-type KLHL9 with the L95F change in its BTB domain and measures impaired CUL3 co-immunoprecipitation. This target-specific domain evidence supports POZ/BTB domain binding. It does not establish equivalent behavior of every CUL3 alternative product. Proposed replacements: POZ domain binding Supporting Evidence: PMID:20554658 Coimmunoprecipitation experiments confirmed that the mutation reduces association with Cullin 3 |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | KEEP AS NON CORE | Reason: The exact anti-tag co-immunoprecipitation record supports binding to KBTBD7. Its identity as a BTB protein is not, by itself, a measurement of the contact domain in this source. Retain the positive association, separately from the stronger domain-mapped BTB-binding annotations. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by... | KEEP AS NON CORE | Reason: Eighty-nine literal affinity/co-immunoprecipitation records represent a mixed CUL3 interactome including BTB adaptors, CAND1, COPS5 and other proteins. The source supports complex associations; no single more specific binding class describes all imported partners. Association is not evidence that every partner is a substrate. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21577200 Tumor-suppressor role for the SPOP ubiquitin ligase in signa... | MODIFY | Reason: PMID:21577200 tests the SPOP BTB interaction with CUL3 using binding constructs and in vitro assays. POZ/BTB domain binding is supported by the operative domain evidence, rather than inferred merely from SPOP containing a BTB domain. Proposed replacements: POZ domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21828050 Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuate... | MODIFY | Reason: The complete PMID:21828050 abstract explicitly describes KLHL7 BTB/BACK-region dependence of CUL3-complex assembly and defective binding of disease mutants. Together with established CUL3–BTB recognition, this supports the more informative POZ-domain binding class; full original assay details remain unavailable. Proposed replacements: POZ domain binding Supporting Evidence: PMID:21828050 assembles with Cul3 through its BTB and BACK domains |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Reason: Five literal two-hybrid records cover SPOP, ELOC, SHKBP1, KLHL5 and BTBD10. This heterogeneous set is retained as measured non-core association; neither POZ-domain recognition nor a ligase-substrate adaptor activity can be assigned to every pair from the screen. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22466964 NEDD8 links cullin-RING ubiquitin ligase function to the p97... | KEEP AS NON CORE | Reason: PMID:22466964 investigates UBXN7 association with neddylated cullins. The main text mentions CUL3 UIM-dependent behavior as data not shown; it does not provide a resolved CUL3 binding interface. Retain the positive curated association with that limitation, not a catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22542517 KBTBD13 interacts with Cullin 3 to form a functional ubiquit... | MODIFY | Reason: PMID:22542517 directly reconstitutes human CUL3 residues 1–383 with the KBTBD13 BTB fragment, residues 6–132. The purified-complex result supports POZ/BTB domain binding and is more precise than unrestricted protein binding. The truncated construct is not a tested full alternative CUL3 product. Proposed replacements: POZ domain binding Supporting Evidence: PMID:22542517 KBTBD13 interacts with Cullin 3 (Cul3) and the BTB domain mediates this interaction |
| GO:0005515 protein binding | IPI PMID:22632832 Adaptor protein self-assembly drives the control of a cullin... | MODIFY | Reason: The source describes CUL3 N-terminal recognition of BTB/BACK adaptor modules, including the SPOP structural complex. This substantiates the shared POZ-domain recognition represented by the SPOP/KLHL1/KLHL20 partner set, with curator deference for the additional reported adaptor assays; it does not imply identical affinity for all adaptors. Proposed replacements: POZ domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | MODIFY | Reason: Two exact PMID:22939624 records identify HSP90AB1, including LUMIER and anti-tag co-immunoprecipitation in human HEK293T cells. Refine to Hsp90 protein binding, which describes the partner class without assigning chaperone or folding activity to CUL3 or claiming an isolated binary interaction. Proposed replacements: Hsp90 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23563313 CCDC22 deficiency in humans blunts activation of proinflamma... | UNDECIDED | Reason: The available PMID:23563313 abstract discusses CCDC22–COMMD regulation, but the CUL3–CCDC22 assay was not independently recovered and no literal pair remains in the inspected export. This absence is not a negative binding result. The specific positive source assertion remains unresolved. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23665031 Disease-causing mutations in KLHL3 impair its effect on WNK4... | KEEP AS NON CORE | Reason: PMID:23665031 directly supports CUL3–KLHL3 association in pull-down experiments alongside WNK4 ubiquitination. The inspected study uses full-length KLHL3 and a dominant-negative CUL3 fragment; it does not isolate the contact domain. Retain positive binding without converting a protein identity into a domain-specific assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Reason: Thirty exact positive screen records cover the imported partner set, with two-hybrid assay and sequence-identity evidence preserved. The set is heterogeneous and includes a retired accession resolved through its archived sequence rather than a guessed symbol. Retain supported generic association; no common more specific class is established for the whole source assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | KEEP AS NON CORE | Reason: The exact positive two-hybrid record supports CUL3–KLHL3 association. The screen does not map the interaction specifically to the BTB domain, so retain the positive generic assertion rather than invent a domain-specific result for this experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25619834 KLHL39 suppresses colon cancer metastasis by blocking KLHL20... | KEEP AS NON CORE | Reason: The original PMID:25619834 supports CUL3 binding to ROC1/RBX1 and KLHL20, so the broad positive binding assertion remains valid. Its IVNS1ABP/KLHL39 arm is different: wild-type KLHL39 fails to bind CUL3 in co-immunoprecipitation and purified assays, whereas engineered F75L/M114L substitutions restore binding. Preserve all imported source fields, but do not treat this partner arm as evidence of wild-type KLHL39 recruitment. The supplementary figure pixels were not inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... | KEEP AS NON CORE | Reason: PMID:25684205 supports CUL3-complex association with KBTBD6 and KBTBD7 and consequent TIAM1 ubiquitination. The retrieved evidence supports the positive partners, but does not independently establish a common isolated contact-domain assay for both in this review. Retain non-core binding alongside the accepted CRL3 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | MODIFY | Reason: PMID:26949739 validates CUL3 association with ACOT7 in SH-SY5Y immunoprecipitation/cross-linking experiments. ACOT7 is an acyl-CoA thioesterase, making thioesterase binding a supported partner-class refinement. The experiment is a cellular association assay, not proof of purified binary binding or thioesterase activity by CUL3. Proposed replacements: thioesterase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27152988 The BTB domains of the potassium channel tetramerization dom... | MODIFY | Reason: The exact PMID:27152988 record describes direct in vitro electron-microscopy analysis of KCTD6 BTB residues 10–110 with CUL3 N-terminal residues 20–381, including a reported 5:5 complex. This is domain-specific support for POZ binding; the stoichiometry pertains to these fragments and is not generalized to all native CRL3 complexes. Proposed replacements: POZ domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30190310 Dimerization quality control ensures neuronal development an... | UNDECIDED | Reason: The complete PMID:30190310 abstract establishes SCF-FBXL17-mediated quality control of BTB dimers, but does not specify the fourteen imported CUL3 partner assays. No literal target records for this citation were recovered from the inspected interaction export. Preserve the positive IPI source and its partners as unresolved rather than infer either nonbinding or a common contact domain from their BTB identities. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Reason: Five exact two-hybrid records support the ABTB1, KLHL2, GMCL1 and KLHL3 partner set. These are positive associations, while the screen does not resolve every contact domain. Retain the generic assertion without deriving a molecular adaptor activity for CUL3 from partner association. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31652307 Kelch-like protein 5-mediated ubiquitination of lysine 183 p... | KEEP AS NON CORE | Reason: The PMID:31652307 abstract supports KLHL5 linking SK1 to CUL3 and attenuation of SK1 degradation by CUL3 depletion or a dominant-negative construct. This supports a CUL3–KLHL5 association, not an independently mapped domain interaction in the material read. Retain it as non-core binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: Forty-seven exact positive HuRI records support the heterogeneous partner set, including the explicitly imported isoforms Q96KE9-2, Q96MP8-2 and Q9H898-2. These are partner products, not target CUL3 isoform assignments. No single more specific binding class covers every retained pair. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Reason: Three exact two-hybrid records support CUL3–HTT association. They establish a physical screen interaction, not that CUL3 is an HTT substrate receptor or that all HTT-associated disease phenotypes are CUL3 functions. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Twenty-two literal anti-tag co-immunoprecipitation records support the source-specific mixed adaptor/regulator interactome. Preserve association scope and the original source tuple; no single domain- or enzyme-binding class represents every partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | KEEP AS NON CORE | Reason: Twenty-one literal anti-tag co-immunoprecipitation records support a mixed set of CUL3 partners, including RBX1, CAND1 and substrate-adaptor proteins. Retain the association evidence without inferring that every detected complex is binary or catalytically active. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | KEEP AS NON CORE | Reason: Seven literal pull-down, co-immunoprecipitation and BRET records support the SPOP/BRAF source set. Its mixed adaptor/kinase scope cannot be narrowed uniformly to kinase binding, and binding does not assign kinase activity to CUL3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | KEEP AS NON CORE | Reason: Six literal anti-bait co-immunoprecipitation records cover HSP90AB1, CKB, COPS5 and BTBD1. These distinct chaperone, enzyme and adaptor partners support generic complex association, without a single specific binding term covering the entire source assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:37788672 Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom... | KEEP AS NON CORE | Reason: The complete PMID:37788672 abstract reports a purified CUL3–RBX1–KLHL22 complex and GDH1-directed ubiquitination assays. Retain association of the scaffold with the RING and adaptor subunits; the pair set cannot be represented solely as POZ binding. This paper is not the disputed KLHL22–DEPDC5 study. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:38225382 Systematic discovery of protein interaction interfaces using... | KEEP AS NON CORE | Reason: The genuine original PMID:38225382 reports a positive CUL3–KCTD7 BRET result, while classifying its predicted interface as likely wrong and declining interface validation. The exact curated record names partner KCTD7-2. Retain measured proximity/association, but do not use the rejected AlphaFold interface to assert a BTB-domain contact or equivalence of all KCTD7 products. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | UNDECIDED | Reason: The target-specific experimental table for PMID:40205054 was not recovered and the inspected interaction export has no literal matches for this source. Independent knowledge of some CUL3 partners does not verify these particular screen assertions. Preserve the positive machine fields and mark the source-specific interaction assessment unresolved, without inferring nonbinding. Supporting Evidence: |
| GO:0001822 kidney development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: The literal mouse donor source PMID:25250572 uses inducible deletion in already developed adult kidney and measures tubular injury, altered homeostasis and later pathology. Those data establish maintenance requirements, not a performed embryonic kidney-development step by CUL3. Preserve the source identity while marking this particular developmental transfer overly broad. Supporting Evidence: GO_REF:0000107 |
| GO:0006954 inflammatory response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: The actual adult-kidney Cul3 deletion study reports injury-associated inflammatory infiltrates. It does not isolate a CUL3-executed inflammatory-response step from secondary renal damage. The mouse transfer is therefore over-annotated at this source, without denying other immune functions of CRL3. Supporting Evidence: GO_REF:0000107 |
| GO:0007229 integrin-mediated signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: The literal mouse source PMID:22358839 connects CUL3–KLHL12-dependent COPII/collagen secretion to extracellular-matrix and integrin-dependent stem-cell behavior. The directly performed step is cargo export; the experiments do not establish CUL3 as an executor of the integrin signaling cascade itself. Preserve the positive phenotype but not its overextended mechanistic classification. Supporting Evidence: GO_REF:0000107 |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: PMID:25250572 quantifies Klhl3 and Cul3 mRNA across nephron segments and measures altered protein abundance, phosphorylation and physiology after adult renal Cul3 deletion. It does not measure CUL3 executing transcription, RNA processing or translation. The inferred GO:0010467 process assignment therefore exceeds this source-specific evidence and remains MARK_AS_OVER_ANNOTATED. This is an overextension from expression measurements and downstream abundance effects, not a contradictory experiment or a denial of other transcription-related CUL3 functions. Supporting Evidence: GO_REF:0000107 |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Reason: The composite electronic evidence includes a genuine mouse ubiquitination annotation and established human CUL3-complex activity. CUL3 contributes structurally to substrate ubiquitination; its lack of a catalytic active site does not negate process participation. Supporting Evidence: GO_REF:0000120 |
| GO:0017145 stem cell division | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: PMID:22358839 links CUL3-dependent collagen export to embryonic-stem-cell maintenance and differentiation. Those phenotypes do not resolve a direct stem-cell division step executed by CUL3, so the transferred division term exceeds the demonstrated secretory mechanism. Supporting Evidence: GO_REF:0000107 |
| GO:0030163 protein catabolic process | IEA GO_REF:0000107 | MODIFY | Reason: The broad mouse-derived protein-catabolism assertion is supported, and the CUL3-dependent ubiquitin/proteasome mechanism is independently established in human cells. Refine to proteasome-mediated ubiquitin-dependent protein catabolism rather than retain an unspecified proteolytic mechanism. Proposed replacements: proteasome-mediated ubiquitin-dependent protein catabolic process Supporting Evidence: GO_REF:0000107 |
| GO:0030332 cyclin binding | IEA GO_REF:0000107 | ACCEPT | Reason: The literal mouse source PMID:10500095 and the actual mammalian cyclin-E experiments support CUL3 binding to free cyclin E. Cyclin binding does not imply cyclin-dependent kinase activity, and it is not invalid merely because CUL3 is a scaffold. Supporting Evidence: GO_REF:0000107 |
| GO:0040016 embryonic cleavage | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Reason: The source PMID:22358839 establishes developmental consequences of defective CUL3-dependent collagen export, but necessity for early embryo viability does not demonstrate a performed cleavage-division step. Preserve the real secretory mechanism and phenotype without this overextended process assignment. Supporting Evidence: GO_REF:0000107 |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | UNDECIDED | Reason: The accessible PMID:22709582 abstract discusses cullin complexes and heteromeric interactions but does not resolve the specific CUL3 homomeric assay behind this mouse-derived identical-protein-binding assertion. Multimeric CRL3 assemblies can contain several CUL3 molecules without establishing direct self-binding. Preserve the donor and positive source tuple as unresolved; incomplete access is not evidence that CUL3 cannot self-associate. Supporting Evidence: GO_REF:0000107 |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The mouse donor PMID:17062563 places the CUL3–actinfilin ubiquitination machinery in a glutamate-receptor turnover context. Neuronal and synaptosomal evidence supports the conserved synaptic pool, while the inspected experiments do not provide a new direct human CUL3 imaging measurement. Retain the transferred localization as non-core. Supporting Evidence: GO_REF:0000107 |
| GO:0140252 regulation protein catabolic process at postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: PMID:17062563 directly connects a CUL3-containing ligase to GluR6 turnover using neuronal assays and Cul3-deficient mouse synaptosomal material. This is performed ubiquitin-dependent receptor regulation at postsynapses, not simply a downstream neurological phenotype. Retain the conserved specialized process. Supporting Evidence: GO_REF:0000107 |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:22542517 KBTBD13 interacts with Cullin 3 to form a functional ubiquit... | ACCEPT | Reason: PMID:22542517 establishes KBTBD13–CUL3 complex assembly and discusses CRL3-dependent proteolysis. The NAS process is consistent with independently proven CUL3 substrate-turnover mechanisms; the purified binding assay alone is not presented as a degradation assay. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:22632832 Adaptor protein self-assembly drives the control of a cullin... | ACCEPT | Reason: PMID:22632832 provides structural context for CRL3 substrate-adaptor recognition. Its NAS catabolic assertion is retained in the broader, well-established CUL3 ubiquitin/proteasome mechanism, without claiming that every crystallographic construct was assayed for degradation. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... | ACCEPT | Reason: PMID:25684205 supports KBTBD6/7–CUL3-dependent TIAM1 ubiquitination and turnover. Retain proteasome-mediated catabolism with the adaptor and cellular context explicit. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:26399832 Cell-fate determination by ubiquitin-dependent regulation of... | ACCEPT | Reason: The source PMID:26399832 principally demonstrates non-degradative TCOF1/NOLC1 ubiquitination. The broad NAS statement about CUL3 proteasomal function remains biologically correct from independent substrate systems, but those TCOF1/NOLC1 experiments are not direct evidence of their proteasomal destruction. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:29249570 Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam... | ACCEPT | Reason: PMID:29249570 is a review of CRL3-dependent differentiation and proteolysis, not a new primary NUFIP1 or ribophagy experiment. The catabolic function is independently established and retained with the original IDA source tuple unchanged; this citation is not presented as a personally inspected direct assay. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:29249570 Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam... | ACCEPT | Reason: The NAS assertion is compatible with the CUL3-dependent substrate-turnover context reported by PMID:29249570 and independently established CRL3 proteolysis. It is not discarded merely because the same publication also has an experimental source row. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:31898230 CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases. | ACCEPT | Reason: PMID:31898230 is a review of BTB–CUL3–RING ligases. Its NAS catabolic assertion is supported by independent CRL3 substrate-turnover experiments; the review is not presented as a new primary degradation assay. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:37628845 The Role of PIK3R1 in Metabolic Function and Insulin Sensiti... | ACCEPT | Reason: PMID:37628845 is a review; its actual paragraph49 describes KBTBD2–CUL3 interaction and p85alpha degradation, citing the original PMID:27708159. Retain the NAS catabolic assertion with that secondary-source status explicit, without converting the reported mouse metabolic phenotypes into direct human CUL3 assays. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:37788672 Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom... | ACCEPT | Reason: PMID:37788672 resolves a CUL3–RBX1–KLHL22/GDH1 assembly and demonstrates GDH1 polyubiquitination in vitro. Retain the curated catabolic assertion with independent CRL3 turnover corroboration; the abstract does not itself report a proteasome assay, and this is not the disputed DEPDC5 nutrient-response study. Supporting Evidence: |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | ACCEPT | Reason: The scaffold activity is independently established by direct CRL3 assembly studies and the specific human complex described in PMID:19782033. The original full text and a reported erratum remain unavailable; neither that limitation nor the erratum listing establishes a contradiction. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Reason: The current HPA record identifies nucleoplasm as a supported location for antibody HPA072059 in the inspected cell contexts. This corroborates the historical IDA nuclear pool without assuming identical localization in all tissues. Supporting Evidence: GO_REF:0000052 |
| GO:0015630 microtubule cytoskeleton | IDA GO_REF:0000052 | KEEP AS NON CORE | Reason: The actual HPA record supports a microtubule-associated pool with cell-line-dependent staining. Retain the contextual localization; this does not make CUL3 a structural microtubule subunit. Supporting Evidence: GO_REF:0000052 |
| GO:0005794 Golgi apparatus | IDA PMID:24145166 Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation... | KEEP AS NON CORE | Reason: PMID:24145166 directly places CUL3–RHOBTB3 machinery at the Golgi and links it to free cyclin-E control. Retain Golgi localization as a real specialized pool. Supporting Evidence: PMID:24145166 a pool of CUL3 was detected on the Golgi, as previously shown (Singer et al., 1999), where it colocalizes with RhoBTB3 and GCC185 (Fig. 4 A). |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... | ACCEPT | Reason: CUL3 proteasomal catabolism is independently established across multiple substrate systems. The particular KLHL22–DEPDC5 mechanism in PMID:29769719 was challenged by PMID:39780017 and defended with different reagent/condition interpretations in PMID:39780003. Retain the broad correct process without treating DEPDC5 turnover as settled. Supporting Evidence: |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... | ACCEPT | Reason: The KEAP1 BTB-dependent CUL3 assembly and NRF2-ubiquitination experiments in PMID:15601839 support the scaffold role. CUL3 brings the substrate-adaptor and RBX1 modules together; it is not being classified as the KEAP1 substrate receptor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15107402 RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligas... | MODIFY | Reason: The complete PMID:15107402 abstract explicitly maps RHOBTB2 binding to CUL3 through its first BTB domain and shows impaired binding of a cancer-associated mutant. POZ/BTB domain binding is therefore supported, although full original methods were not recovered; the tumor-suppressor substrate-recruitment model is distinguished from the measured binding. Proposed replacements: POZ domain binding Supporting Evidence: PMID:15107402 Cul3, via its first BTB domain |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... | ACCEPT | Reason: The complete PMID:23453970 abstract supports KLHL3–CUL3 complex-mediated WNK kinase ubiquitination. Retain the scaffold assignment with the original source and construct scope, not an autonomous ubiquitin-transfer claim. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:35862218 ARMC5-CUL3 E3 ligase targets full-length SREBF in adrenocort... | ACCEPT | Reason: PMID:35862218 supports CUL3–ARMC5 complex membership through BTB-dependent association and HEK293T co-immunoprecipitation. Mouse Srebf/Armc5 and 3T3-L1 discovery experiments remain distinct from human-cell assays; no universal adrenocortical phenotype is assigned to CUL3. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:35687106 ARMC5 is part of an RPB1-specific ubiquitin ligase implicate... | ACCEPT | Reason: PMID:35687106 demonstrates human CUL3–ARMC5 association and reconstitutes RPB1 ubiquitination with CUL3/RBX1, ARMC5, E1, UBE2E1 and ubiquitin. The whole-complex 3D depiction is a model, not a solved structure; these limits do not negate CRL3 membership. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:38225631 ARMC5 controls the degradation of most Pol II subunits, and ... | ACCEPT | Reason: PMID:38225631 supports human CUL3–ARMC5/POLR2A association in SK-N-SH cells with separate mouse neural-progenitor turnover experiments. Retain CRL3 membership without asserting direct ubiquitination of every RNA polymerase II subunit. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:39504960 Redundant pathways for removal of defective RNA polymerase I... | ACCEPT | Reason: PMID:39504960 establishes ARMC5-dependent CUL3–RNAPII association in human HEK293-derived cells. This supports the CUL3 complex, distinct from the RNA-capping and Integrator functions used to define its context. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:39667934 CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form... | ACCEPT | Reason: PMID:39667934 combines a human CUL3 siRNA screen with ARMC5 perturbation and RPB1-turnover evidence. These data and the other ARMC5 studies support CUL3-containing ligase membership while endogenous ARMC5 antibody limitations remain explicit. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:35687106 ARMC5 is part of an RPB1-specific ubiquitin ligase implicate... | ACCEPT | Reason: The actual PMID:35687106 reconstitution modifies RPB1, while cellular proteasome and mouse-knockout experiments support degradation. CUL3 performs the ligase scaffold step; it is neither an RNA polymerase subunit nor the proteasome itself. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:38225631 ARMC5 controls the degradation of most Pol II subunits, and ... | ACCEPT | Reason: PMID:38225631 supports CUL3–ARMC5-dependent proteasomal turnover of RNA polymerase II machinery, with human-cell ubiquitination and separate mouse neural experiments. Direct modification of all twelve polymerase subunits was not established, and POLR2C increase was not statistically significant. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:39504960 Redundant pathways for removal of defective RNA polymerase I... | ACCEPT | Reason: PMID:39504960 supports basal Ser5-phosphorylated RPB1 ubiquitination and proteasomal turnover by ARMC5–CUL3 machinery. Preserve the distinction from UV-induced elongation-associated turnover; CUL3 is not assigned RNA-capping activity. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:39667934 CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form... | ACCEPT | Reason: PMID:39667934 supports CUL3-dependent, ARMC5-regulated RPB1 turnover using human-cell perturbations, p97/proteasome sensitivity and half-life measurements. The early-transcription pathway remains distinct from K1268-dependent DNA-damage turnover; no new polymerase activity is inferred. Supporting Evidence: |
| GO:0034599 cellular response to oxidative stress | IDA PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... | KEEP AS NON CORE | Reason: KEAP1–CUL3-mediated NRF2 turnover in PMID:15601839 directly mediates an oxidative-stress response. Retain this specialized process alongside the general scaffold core. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... | ACCEPT | Reason: PMID:15601839 links a KEAP1–CUL3 ligase to NRF2 ubiquitination and turnover. The scaffold provides a structural part of the pathway and thus participates in proteasomal catabolism. Supporting Evidence: |
| GO:0071230 cellular response to amino acid stimulus | IDA PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... | UNDECIDED | Reason: The CUL3–KLHL22/DEPDC5 nutrient-response mechanism in PMID:29769719 is substantively disputed. PMID:39780017 found no amino-acid-dependent DEPDC5 turnover or KLHL22 requirement under its antibody, medium and knockout conditions; PMID:39780003 argues for reagent/condition differences and a regulated subpopulation. The available original and reply do not resolve this specific signaling assertion across conditions. Preserve the positive source tuple without declaring the result universally false. Supporting Evidence: |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... | ACCEPT | Reason: The CUL3 scaffold activity is independently established and also represented in the purified KLHL22 complex used by PMID:29769719. Its specific DEPDC5/TORC1 interpretation is disputed by PMID:39780017 and the reply PMID:39780003; that dispute does not invalidate the general scaffold activity or all CUL3–KLHL22 complexes. Supporting Evidence: |
| GO:1904263 positive regulation of TORC1 signaling | IDA PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... | UNDECIDED | Reason: The CUL3–KLHL22/DEPDC5 nutrient-response mechanism in PMID:29769719 is substantively disputed. PMID:39780017 found no amino-acid-dependent DEPDC5 turnover or KLHL22 requirement under its antibody, medium and knockout conditions; PMID:39780003 argues for reagent/condition differences and a regulated subpopulation. The available original and reply do not resolve this specific signaling assertion across conditions. Preserve the positive source tuple without declaring the result universally false. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... | ACCEPT | Reason: PMID:23453970 supports KLHL3–CUL3-dependent WNK kinase ubiquitination and proteasomal control. Preserve the positive process while distinguishing KLHL3 substrate recognition from CUL3 scaffold activity. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... | KEEP AS NON CORE | Reason: The source PMID:27708159 supports a cytoplasmic CUL3–KBTBD2 complex. The location is compatible with independently measured CUL3 pools and does not follow merely from absence of a signal peptide. Supporting Evidence: |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... | ACCEPT | Reason: The source PMID:27708159 supports a CUL3–KBTBD2 ligase producing K48-linked ubiquitination of p85alpha. The specific chain-type assertion is retained with experimental-curator deference; mouse metabolic phenotypes do not imply that every assay was human. Supporting Evidence: |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... | ACCEPT | Reason: PMID:27708159 maps KBTBD2 recruitment to CUL3 and places CUL3 in the p85alpha-directed ubiquitin ligase. The target therefore performs scaffold activity, independently of the downstream insulin-response phenotype. Supporting Evidence: |
| GO:1900076 regulation of cellular response to insulin stimulus | IDA PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... | KEEP AS NON CORE | Reason: PMID:27708159 connects CUL3–KBTBD2-dependent p85alpha degradation to insulin responsiveness. Preserve the source-specific regulatory outcome; the strong mouse adipose phenotypes are not mislabeled as human CUL3 knockouts. Supporting Evidence: |
| GO:0032480 negative regulation of type I interferon production | IDA PMID:36394357 XAF1 prevents hyperproduction of type I interferon upon vira... | KEEP AS NON CORE | Reason: PMID:36394357 reports negative control of IRF7/type-I-interferon output through a CUL3-containing ubiquitination system. Retain this immune context without treating all interferon effects as the universal role of CUL3. Supporting Evidence: |
| GO:0160072 ubiquitin ligase complex scaffold activity | IDA PMID:36394357 XAF1 prevents hyperproduction of type I interferon upon vira... | ACCEPT | Reason: The complete PMID:36394357 abstract supports an XAF1-regulated KLHL22–CUL3 complex that controls IRF7 through K48-linked ubiquitination. The target scaffold activity is coherent; the original full methods were not available, and this is not evidence about DEPDC5. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IMP PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... | ACCEPT | Reason: The KBTBD6/7–CUL3 mechanism in PMID:25684205 controls TIAM1 by ubiquitination and degradation. Preserve the perturbation-based catabolic assertion without assigning TIAM1 exchange-factor activity to CUL3. Supporting Evidence: |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... | ACCEPT | Reason: The original source supports K48-linked ubiquitination by a CUL3-containing complex. Retain the chain-type process as performed structural participation, not intrinsic catalysis by the cullin alone. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... | ACCEPT | Reason: PMID:25684205 establishes KBTBD6/7–CUL3–RBX1 complex membership. The specific CRL3 component annotation is supported by its molecular role and positive binding evidence. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28169274 Armc5 deletion causes developmental defects and compromises ... | KEEP AS NON CORE | Reason: PMID:28169274 uses a human ARMC5 bait, a sequenced CUL3 prey and mammalian co-immunoprecipitation to establish association. Mouse Armc5 phenotypes are not human CUL3 binding experiments. Retain the positive molecular association without manufacturing a separate binding-domain or catalytic function. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:19617556 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation ... | KEEP AS NON CORE | Reason: The actual PMID:19617556 experiments show DCNL3-dependent recruitment of CUL3 to the plasma membrane. A peripheral, partner-recruited pool satisfies localization without a CUL3 transmembrane helix; the prior absence-of-TM objection was not sufficient. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26906416 Characterization of the mammalian family of DCN-type NEDD8 E... | KEEP AS NON CORE | Reason: The actual PMID:26906416 main text and purified-protein methods support CUL3 binding to all five DCNL proteins, including CUL3–RBX1–CAND1 complexes and DCNL-dependent neddylation. This does not make CUL3 the NEDD8-transfer catalyst, and later CUL4A DNA-repair experiments are not CUL3 assays. Retain the DCNL association assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24192928 Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylatio... | KEEP AS NON CORE | Reason: PMID:24192928 supports DCUN1D1/DCUN1D5 binding to cullins in HeLa and in vitro neddylation studies. Preserve CUL3 association while separating the DCNL cofactor role from CUL3 as the modified cullin substrate and CRL scaffold. Supporting Evidence: |
| GO:0000209 protein polyubiquitination | IDA PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | ACCEPT | Reason: PMID:14528312 reconstitutes polyubiquitination with MEL-26–CUL3–ROC1 and E1/E2/ubiquitin components. CUL3 supplies the assembly scaffold, and the process statement is valid despite the comparative worm adaptor/substrate components. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | MODIFY | Reason: PMID:14528312 provides direct CUL3 recognition of BTB/POZ substrate adaptors, including comparative worm MEL-26 and human BTB proteins. Refine generic protein binding to POZ domain binding; species and construct boundaries do not imply that every developmental phenotype in the paper was measured for human CUL3. Proposed replacements: POZ domain binding Supporting Evidence: PMID:14528312 Cul3, but not other cullins, binds directly to multiple BTB domains |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | ACCEPT | Reason: The original PMID:14528312 assembly experiments establish CUL3–ROC1 complexes with BTB substrate adaptors. The specific complex membership is directly supported. Supporting Evidence: |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | ACCEPT | Reason: The original complex assay supports CUL3 binding to the RBX1 RING ubiquitin-ligase subunit. Ubiquitin protein ligase binding is a valid association claim and does not itself assert autonomous ubiquitin-transfer activity by CUL3. Retain it separately from the more informative scaffold core. Supporting Evidence: |
| GO:0051865 protein autoubiquitination | IDA PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | UNDECIDED | Reason: PMID:14528312 describes CUL3-complex auto-ubiquitin-ligase activity in supplementary assays. The personally inspected main text does not resolve whether the annotation denotes modification of CUL3 itself, another subunit or ligase-associated substrate, and the decisive supplementary assay was not recovered. Keep the exact positive IDA source unresolved rather than interpret it as autonomous self-catalysis. Supporting Evidence: |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | MODIFY | Reason: PMID:14528312 demonstrates an active CUL3–ROC1–BTB ubiquitin-ligase complex. The gene product supplies the scaffold connecting ROC1 and the substrate adaptor; the more precise scaffold activity captures its own performed role without denying complex-level catalysis. This unqualified activity row is distinct from the explicitly contributes_to transferase rows retained elsewhere. Proposed replacements: ubiquitin ligase complex scaffold activity Supporting Evidence: |
| GO:0031208 POZ domain binding | IDA PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... | ACCEPT | Reason: PMID:14528312 directly maps CUL3 N-terminal binding to BTB/POZ domains using deletions, recombinant proteins and multiple adaptor-domain constructs. The existing specific binding term is well supported. Supporting Evidence: |
| GO:0000922 spindle pole | IDA PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | KEEP AS NON CORE | Reason: PMID:23213400 directly observes CUL3 at spindle poles in its mitotic context. Preserve localization, separate from intrinsic Aurora kinase activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | KEEP AS NON CORE | Reason: PMID:23213400 supports CUL3-complex association with both KLHL18 and Aurora-A during mitotic regulation. This mixed adaptor/kinase assertion is retained as positive association; kinase binding cannot describe the entire pair set and kinase activity belongs to Aurora-A. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | ACCEPT | Reason: The actual PMID:23213400 localization experiments support a nuclear CUL3 pool in addition to its mitotic sites. Retain the broad location without collapsing cell-cycle-dependent distributions. Supporting Evidence: |
| GO:0005813 centrosome | IDA PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | KEEP AS NON CORE | Reason: The same primary imaging supports centrosomal CUL3. This is a cell-cycle-regulated pool and is retained as non-core rather than dismissed because other CRL3 complexes are cytosolic. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | ACCEPT | Reason: PMID:23213400 links CUL3–KLHL18-dependent ubiquitination to Aurora-A regulation. This is a non-degradative ubiquitination mechanism and need not be forced into proteasomal catabolism. Supporting Evidence: |
| GO:0072686 mitotic spindle | IDA PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | KEEP AS NON CORE | Reason: PMID:23213400 supports mitotic-spindle localization of CUL3. Retain the observed subcellular context without implying every CUL3 molecule is spindle bound. Supporting Evidence: |
| GO:1901992 positive regulation of mitotic cell cycle phase transition | IMP PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... | KEEP AS NON CORE | Reason: The CUL3–KLHL18/Aurora-A perturbation experiments support a positive contribution to mitotic entry/progression. This is a specific functional regulatory context, not the molecular activity itself. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29276004 Missense Variants in RHOBTB2 Cause a Developmental and Epile... | UNDECIDED | Reason: PMID:29276004 provides RHOBTB2 disease and turnover evidence, but the exact target-specific CUL3-binding experiment was not independently recovered from the available abstract and has no literal record in the inspected export. Retain the original positive tuple as unresolved rather than infer a false interaction from missing access. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:28395323 Defining the human sperm microtubulome: an integrated genomi... | ACCEPT | Reason: PMID:28395323 explicitly includes CUL3 experimental expression/localization analyses. The title or prominence of DCDC2C does not justify rejecting the curated cytoplasmic observation. Preserve the positive source with the available-abstract/full-text limitation stated. Supporting Evidence: |
| GO:0036126 sperm flagellum | IDA PMID:28395323 Defining the human sperm microtubulome: an integrated genomi... | KEEP AS NON CORE | Reason: The PMID:28395323 abstract explicitly includes experimental CUL3 sperm-flagellar expression patterns, so its curated positive localization is retained. Current HPA sperm staining with another context does not negate that historical experiment; full original imaging was not recovered. Supporting Evidence: |
| GO:0031398 positive regulation of protein ubiquitination | IGI PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... | KEEP AS NON CORE | Reason: The miR-101/CUL3/NRF2 study PMID:24844779 supports a positive CUL3 influence on ubiquitination. Retain the contextual regulatory assertion; altered miRNA expression alone is not used to manufacture a new function. Supporting Evidence: |
| GO:0031648 protein destabilization | IGI PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... | KEEP AS NON CORE | Reason: PMID:24844779 supports CUL3-dependent destabilization in the NRF2 pathway. Preserve this specific cellular outcome without elevating every substrate-related phenotype to core status. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22748208 A homozygous mutation in KCTD7 links neuronal ceroid lipofus... | KEEP AS NON CORE | Reason: The complete PMID:22748208 abstract reports that the KCTD7 Arg184Cys change abolishes interaction with CUL3, supporting the wild-type positive association. That residue result is not a direct demonstration of an isolated BTB contact in the material read. Retain measured binding without a stronger domain claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23776465 Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear lo... | KEEP AS NON CORE | Reason: PMID:23776465 demonstrates incorporation of COPS9/CSNAP into the COP9 signalosome and co-purification with cullins, including CUL3. The imported COPS9-2 is a noncatalytic partner isoform; complex association does not assign COP9 deneddylase activity to either CSNAP or CUL3. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:26399832 Cell-fate determination by ubiquitin-dependent regulation of... | ACCEPT | Reason: PMID:26399832 demonstrates the CUL3–KBTBD8 complex used in non-degradative TCOF1/NOLC1 ubiquitination. Complex membership is directly supported even though these substrates are not degraded in that mechanism. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8932327 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8932327 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952631 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8952631 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8956040 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8956040 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712274 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9712274 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9755505 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9755505 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9755507 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9755507 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9758090 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9758090 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9759169 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9759169 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9759172 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9759172 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9766645 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9766645 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9766656 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9766656 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9766677 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9766677 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9766687 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9766687 |
| GO:0005112 Notch binding | IPI PMID:25401743 KCTD10 is involved in the cardiovascular system and Notch si... | ACCEPT | Reason: The actual PMID:25401743 cellular experiments support CUL3 association with full-length Notch1, together with reduced receptor abundance and signaling in the relevant HUVEC context. Notch binding is a valid partner-specific activity even if mediated within a complex; it does not assert direct purified contact or binding to isolated Notch intracellular domain. Supporting Evidence: |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:25401743 KCTD10 is involved in the cardiovascular system and Notch si... | ACCEPT | Reason: The actual Notch1 experiments in PMID:25401743 support CUL3-complex-dependent ubiquitination and receptor destabilization. This is a performed ubiquitin-dependent catabolic role, separate from ligand/receptor signaling activities of Notch. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26334369 Structural Insights into KCTD Protein Assembly and Cullin3 R... | MODIFY | Reason: PMID:26334369 directly analyzes KCTD9 BTB assemblies with CUL3 and reports high-affinity complex formation. POZ/BTB domain binding is therefore an experimentally grounded refinement, not just an inference from KCTD9 nomenclature. Proposed replacements: POZ domain binding Supporting Evidence: PMID:26334369 confirm the 5:5 assembly of KCTD9/Cul3 complexes |
| GO:0005515 protein binding | IPI PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... | KEEP AS NON CORE | Reason: The actual PMID:27561354 source establishes CUL3-associated KLHL15-dependent CtIP turnover in human cells. Association of CtIP/RBBP8 with a CUL3 complex is supported, while substrate recruitment is not evidence that CUL3 directly recognizes every CtIP surface or has nuclease activity. Supporting Evidence: |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... | ACCEPT | Reason: PMID:27561354 demonstrates CUL3/KLHL15-dependent CtIP ubiquitination and turnover. CUL3 supplies scaffold activity in this catabolic mechanism; the data do not by themselves classify CtIP as a damaged or misfolded protein. Supporting Evidence: |
| GO:0071630 nuclear protein quality control by the ubiquitin-proteasome system | IDA PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... | MODIFY | Reason: PMID:27561354 establishes regulated CtIP ubiquitination/turnover, but the inspected experiments do not classify CtIP as a misfolded, damaged or unassembled nuclear quality-control substrate. Refine to the demonstrated proteasome-mediated ubiquitin-dependent catabolic process; the more restrictive quality-control mechanism is not established. Proposed replacements: proteasome-mediated ubiquitin-dependent protein catabolic process Supporting Evidence: PMID:27561354 CUL3-KLHL15 catalyses polyubiquitination and proteasome-dependent degradation of CtIP |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IDA PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S ... | MODIFY | Reason: The actual PMID:10500095 mechanism involves CUL3-dependent turnover of free cyclin E, not catalysis by anaphase-promoting complex. GO:0031145 explicitly requires APC-dependent proteasomal catabolism. Preserve the demonstrated catabolic biology using the corresponding ubiquitin/proteasome process rather than an APC-specific term. Proposed replacements: proteasome-mediated ubiquitin-dependent protein catabolic process Supporting Evidence: PMID:10500095 overexpression of Cul-3 increased ubiquitination of cyclin E |
| GO:0005515 protein binding | IPI PMID:25270598 Ubiquitin-proteasome system controls ciliogenesis at the ini... | MODIFY | Reason: PMID:25270598 maps CUL3 association to the KCTD17 BTB-containing region and reconstitutes the CUL3–RBX1–KCTD17 pathway acting on trichoplein. POZ domain binding captures the measured recognition without confusing CUL3 scaffold function with KCTD17 substrate recognition. Proposed replacements: POZ domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21778237 COMMD1 (copper metabolism MURR1 domain-containing protein 1)... | UNDECIDED | Reason: The complete PMID:21778237 abstract establishes COMMD-family regulation of cullin complexes, but the individual CUL3–COMMD partner assays in this imported multi-partner assertion were not recovered. The lack of literal matches in the current interaction export is not negative evidence. Keep the exact source tuple unresolved pending those assays. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5635854 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain nucleoplasmic localization in the SPOP/GLI complex context. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-5635854 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5635855 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain nucleoplasmic localization in the SPOP/GLI complex context. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-5635855 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5635856 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain nucleoplasmic localization in the SPOP/GLI complex context. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-5635856 |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... | KEEP AS NON CORE | Reason: PMID:17543862 supports CUL3-dependent mitotic chromosome alignment through regulated ubiquitination. Retain the experimentally measured cell-cycle process as a specialized CRL3 context. Supporting Evidence: |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... | KEEP AS NON CORE | Reason: Actual PMID:19995937 experiments link CUL3-dependent Aurora-B regulation to chromosome alignment. This is a performed regulatory mechanism, not merely an association with mitotic cells. Supporting Evidence: |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | IMP PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... | KEEP AS NON CORE | Reason: The mitotic perturbation evidence supports positive control of metaphase/anaphase progression by CUL3-containing ligases. Retain the contextual process without confusing CUL3 with the APC/C complex. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:24768539 K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ub... | ACCEPT | Reason: The complete PMID:24768539 abstract and curated evidence support a CUL3-containing ligase complex. Preserve the defining component role without inventing exact subunit stoichiometry from an abstract-only source. Supporting Evidence: |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | UNDECIDED | Reason: The source PMID:19946888 is a membrane-enriched YTS-cell proteomic screen. Its abstract includes many peripheral or uncertain membrane-associated identifications, and the target-specific CUL3 table entry was not recovered. Independent DCNL3-mediated plasma-membrane recruitment cannot authenticate this particular HDA screen. Preserve the source assertion as unresolved rather than infer absence from CUL3 lacking transmembrane segments. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Reason: The preserved original NHLBI urinary-exosome database accompanying PMID:19056867 identifies CUL3/NP_003581 at zero-based HTML row 325 with one peptide. Retain this curated HDA compartment detection as KEEP_AS_NON_CORE, with limited single-peptide support. GO:0070062 is a cellular-component term: it does not require CUL3 to execute an extracellular reaction. This preparation-specific identification does not establish constitutive secretion, luminal versus surface topology, or extracellular catalytic activity, and those broader claims are not made. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:19158078 Control of rapsyn stability by the CUL-3-containing E3 ligas... | ACCEPT | Reason: The complete PMID:19158078 abstract supports CUL3-complex association in the BTB-adaptor system studied. The specific CRL3 component assignment is coherent with the experimentally established human scaffold. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:22578813 Translational homeostasis via the mRNA cap-binding protein, ... | ACCEPT | Reason: PMID:22578813 establishes a CUL3–KLHL25 complex acting on unbound hypophosphorylated 4E-BP1. This supports CRL3 membership, not a generic claim that all eIF4E-bound 4E-BP1 is degraded. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... | ACCEPT | Reason: The KLHL3–CUL3 WNK-regulatory system in PMID:23453970 is a specific CRL3 complex. Retain the original IDA complex membership rather than infer an autonomous catalytic activity. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:23576762 Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis v... | ACCEPT | Reason: The complete PMID:23576762 abstract supports the CUL3-containing complex in its substrate-adaptor context. Retain the source-specific CRL3 membership with honest full-original access limits. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18397884 Regulation of TIP60 by ATF2 modulates ATM activation. | KEEP AS NON CORE | Reason: PMID:18397884 supports association of CUL3 with ATF2/TIP60 machinery that regulates TIP60 turnover. The mixed transcription-factor/acetyltransferase set supports complex association, not a uniform enzyme-binding refinement or transcription-factor activity by CUL3. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1504190 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-1504190 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1504193 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-1504193 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1504213 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-1504213 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5658424 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-5658424 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952630 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8952630 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955241 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8955241 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955289 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-8955289 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9018778 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9018778 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9018787 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9018787 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706390 | ACCEPT | Reason: The saved current Reactome graph explicitly reaches the Q13618 CUL3 reference entity through the annotated event and its complex components. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9706390 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9929484 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9929484 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9929486 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9929486 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9929490 | ACCEPT | Reason: The selected Reactome event explicitly describes a CUL3-containing complex in this compartment; some nested current graph entities remain unresolved after a bounded retrieval, so a complete new target-path reconstruction is not claimed. Retain the cytosolic CUL3 pool represented in this event. Event membership does not transfer neighboring UBE2M NEDD8-transfer, COP9 deneddylase, proteasome or adaptor activities to CUL3; independent primary localization corroborates the broad compartment. Supporting Evidence: Reactome:R-HSA-9929490 |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:23455478 Ubiquitylation-dependent localization of PLK1 in mitosis. | ACCEPT | Reason: PMID:23455478 establishes a CUL3–RBX1–KLHL22 complex that modifies PLK1 and regulates its kinetochore localization. The Sf9 CUL3–RBX1/bacterial KLHL22 reconstitution supports complex membership; it does not show CUL3 kinase activity or proteasomal PLK1 degradation. Supporting Evidence: |
| GO:0000209 protein polyubiquitination | IDA PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | ACCEPT | Reason: PMID:19261606 links a CUL3–KLHL42 complex to p60 katanin ubiquitin laddering and turnover. This supports polyubiquitination at the assembled-ligase level, with comparative human/mammalian constructs kept distinct. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | ACCEPT | Reason: The source explicitly qualifies this as contributes_to ubiquitin-protein transferase activity. PMID:19261606 demonstrates the CUL3-containing ligase acting on p60 katanin; a structural contribution is a valid weaker assertion and is not contradicted by CUL3 lacking autonomous catalysis. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | KEEP AS NON CORE | Reason: PMID:19261606 demonstrates CUL3 association with KLHL42/KLHDC5 and a p60 katanin-containing complex. The purified or cellular complex context does not imply direct CUL3–katanin contact. Retain this combined adaptor/substrate binding assertion separately from the genuine POZ-binding and ubiquitination annotations. Supporting Evidence: |
| GO:0031208 POZ domain binding | IDA PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | ACCEPT | Reason: The actual PMID:19261606 screen and deletion experiments support BTB/POZ adaptor binding through the CUL3 N terminus. The experimental exon-2 deletion bait is not silently equated with a full-length alternative product. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | ACCEPT | Reason: The CUL3–KLHL42/KLHDC5 complex in PMID:19261606 supports the specific CRL3 membership. Partner and historical-symbol identities are preserved. Supporting Evidence: |
| GO:0032467 positive regulation of cytokinesis | IMP PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | KEEP AS NON CORE | Reason: PMID:19261606 demonstrates CUL3/KLHL42-dependent p60 regulation and abnormal postmitotic bridges after perturbation. Preserve positive cytokinesis regulation as a substrate-specific outcome, not a claim of direct contractile-ring catalysis. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... | ACCEPT | Reason: PMID:19261606 couples CUL3-dependent p60 katanin ubiquitination to increased p60 abundance after CUL3 loss. Retain the ubiquitin/proteasome catabolic role in that mitotic substrate context. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:15983046 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote... | ACCEPT | Reason: This is explicitly contributes_to ubiquitin-protein transferase activity. PMID:15983046 describes ubiquitination by a CUL3-containing complex, so the scaffold contribution is valid without claiming CUL3 alone catalyzes transfer. The activity is not replaced merely to repeat the scaffold core. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:15983046 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote... | ACCEPT | Reason: PMID:15983046 supports CUL3-containing complexes with BTB/Kelch partners. Preserve this direct complex-membership assertion, separately from the different degradation routes of individual ubiquitinated partners. Supporting Evidence: |
| GO:0006513 protein monoubiquitination | IDA PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... | KEEP AS NON CORE | Reason: The actual PMID:22358839 experiments establish SEC31 monoubiquitination by CUL3–KLHL12. The non-degradative modification is retained separately from polyubiquitin-dependent substrate destruction. Supporting Evidence: |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IDA PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... | KEEP AS NON CORE | Reason: CUL3–KLHL12-dependent SEC31 modification changes COPII coat size and collagen export in PMID:22358839. CUL3 performs a regulatory ubiquitination step of ER-to-Golgi trafficking, not merely being cargo of the pathway. Supporting Evidence: |
| GO:0007229 integrin-mediated signaling pathway | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Reason: The literal mouse source PMID:22358839 connects CUL3–KLHL12-dependent COPII/collagen secretion to extracellular-matrix and integrin-dependent stem-cell behavior. The directly performed step is cargo export; the experiments do not establish CUL3 as an executor of the integrin signaling cascade itself. Preserve the positive phenotype but not its overextended mechanistic classification. The ISS source tuple is retained separately from its electronic counterpart. Supporting Evidence: GO_REF:0000024 |
| GO:0017145 stem cell division | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Reason: PMID:22358839 links CUL3-dependent collagen export to embryonic-stem-cell maintenance and differentiation. Those phenotypes do not resolve a direct stem-cell division step executed by CUL3, so the transferred division term exceeds the demonstrated secretory mechanism. The ISS source tuple is retained separately from its electronic counterpart. Supporting Evidence: GO_REF:0000024 |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... | ACCEPT | Reason: The original PMID:22358839 establishes CUL3–KLHL12 complex assembly and SEC31 ubiquitination. This is a genuine CRL3 complex in a non-degradative COPII regulation context. Supporting Evidence: |
| GO:0040016 embryonic cleavage | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Reason: The source PMID:22358839 establishes developmental consequences of defective CUL3-dependent collagen export, but necessity for early embryo viability does not demonstrate a performed cleavage-division step. Preserve the real secretory mechanism and phenotype without this overextended process assignment. The ISS source tuple is retained separately from its electronic counterpart. Supporting Evidence: GO_REF:0000024 |
| GO:0048208 COPII vesicle coating | IMP PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... | KEEP AS NON CORE | Reason: The same direct SEC31 modification and coat-size experiments support CUL3 participation in COPII vesicle coating. Preserve that performed regulatory contribution without assigning CUL3 the structural-coat-subunit role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18826954 SCCRO (DCUN1D1) is an essential component of the E3 complex ... | UNDECIDED | Reason: The curated IPI assertion names the CUL3–DCUN1D1 pair, but no literal record for that source pair was recovered in the current interaction exports. The complete PMID:18826954 abstract describes cullin–ROC1 machinery and Cul1 experiments without resolving the CUL3-specific assay, and the full original remains unavailable. Independent DCNL–CUL3 work in PMID:26906416 supports the association biologically but does not verify this precise source assertion. Preserve the positive source tuple unresolved, without inferring nonbinding or transferring NEDD8 catalytic activity to CUL3. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | ACCEPT | Reason: This source explicitly asserts contributes_to ubiquitin-protein transferase activity, not autonomous catalysis. PMID:19782033 describes an active CUL3–BACURD complex; the full original and erratum remain unavailable, but the abstract and independent CRL3 evidence support the curated structural contribution. Preserve the valid contribution alongside the scaffold core. Supporting Evidence: |
| GO:0016477 cell migration | IMP PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | KEEP AS NON CORE | Reason: PMID:19782033 links CUL3–BACURD RhoA turnover to cell migration. Retain the contextual experimentally curated phenotype, with the original full text and erratum contents still unavailable. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | ACCEPT | Reason: The CUL3–BACURD RhoA-control mechanism in PMID:19782033 supports ubiquitination by a CUL3-containing complex. Preserve the positive curated result, while the inaccessible full paper and unrecovered erratum limit a new assay-level reinterpretation. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | ACCEPT | Reason: The source supports a BACURD–CUL3 ligase complex. Its specific membership remains valid alongside independent CRL3 assembly evidence; an erratum listing without its contents is not evidence for withdrawal. Supporting Evidence: |
| GO:0035024 negative regulation of Rho protein signal transduction | IMP PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | KEEP AS NON CORE | Reason: The source describes CUL3–BACURD-mediated RhoA degradation, which supports negative regulation of Rho signaling. This does not make CUL3 a Rho GTPase, GAP or GDI. Supporting Evidence: |
| GO:0043149 stress fiber assembly | IMP PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | KEEP AS NON CORE | Reason: The source-specific RhoA turnover mechanism affects stress-fiber assembly. Preserve the positive contextual process with the original evidence, rather than replace it by an unsupported direct actin-binding activity. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... | ACCEPT | Reason: PMID:19782033 reports CUL3–BACURD-mediated RhoA ubiquitination and proteasomal turnover. Retain the experimentally curated catabolic process with source-access limitations explicit. Supporting Evidence: |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IDA PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... | ACCEPT | Reason: The actual PMID:20389280 E1/UbcH5a/ubiquitin/ATP assays and cellular turnover experiments support CUL3–ROC1–KLHL20-dependent DAPK ubiquitination and proteasomal degradation. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... | ACCEPT | Reason: This source explicitly asserts contributes_to ubiquitin-protein transferase activity, not autonomous catalysis. The actual PMID:20389280 CUL3–ROC1–KLHL20 preparation ubiquitinates DAPK with E1, UbcH5a, ubiquitin and ATP, and CUL3-contact deletion controls establish the assembly contribution. Preserve the valid contribution alongside the scaffold core. Supporting Evidence: |
| GO:0005827 polar microtubule | IDA PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... | KEEP AS NON CORE | Reason: Actual PMID:19995937 identifies CUL3 on polar microtubules during mitosis. Retain this observed localization without transferring Aurora-B kinase activity to CUL3. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... | ACCEPT | Reason: PMID:17543862 directly implicates CUL3 complexes in mitotic substrate ubiquitination. Retain the performed process rather than treating the mitotic setting as evidence of over-annotation. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... | ACCEPT | Reason: PMID:19995937 demonstrates non-degradative Aurora-B ubiquitination by CUL3-containing ligases and its spatial regulation at mitosis. Ubiquitination is supported without imposing a degradation outcome. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... | ACCEPT | Reason: The original PMID:20389280 reconstituted CUL3–ROC1–KLHL20 system supports DAPK ubiquitination. CUL3 supplies the structural connection required for this chemistry. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... | ACCEPT | Reason: PMID:17543862 identifies the CUL3–KLHL9/KLHL13 mitotic ubiquitin-ligase complex. Preserve the specific complex-membership annotation. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... | ACCEPT | Reason: PMID:19995937 supports CUL3-based mitotic ligases controlling Aurora-B localization. Complex membership remains distinct from the downstream chromosome-segregation phenotype. Supporting Evidence: |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... | ACCEPT | Reason: PMID:20389280 directly establishes CUL3–ROC1–KLHL20 complex assembly with DAPK-directed function. The annotation is specific and well grounded. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18573101 KCTD5, a putative substrate adaptor for cullin3 ubiquitin li... | MODIFY | Reason: The complete PMID:18573101 abstract explicitly requires the KCTD5 BTB domain and N-terminal region for CUL3 interaction. This is evidence for POZ/BTB domain recognition, although full original methods remain unavailable. The binding class is more informative than generic association. Proposed replacements: POZ domain binding Supporting Evidence: PMID:18573101 in addition to the BTB domain, some amino acids in the N-terminus of KCTD5 are required for binding to cullin3 |
| GO:0000082 G1/S transition of mitotic cell cycle | TAS PMID:8681378 cul-1 is required for cell cycle exit in C. elegans and iden... | KEEP AS NON CORE | Reason: The cited PMID:8681378 focuses on worm CUL-1, so it is not direct human CUL3 assay evidence. Independent mammalian CUL3/free-cyclin-E experiments in PMID:10500095 support G1/S regulation; retain the biologically sound contextual assertion with that source distinction, not a wrong-gene verdict from an abstract. Supporting Evidence: |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:9733711 Cloning and expression analysis of a novel salicylate suppre... | UNDECIDED | Reason: The complete PMID:9733711 abstract measures CUL3 expression during PMA-induced differentiation and salicylate treatment and proposes a connection to proliferation. Expression changes alone do not resolve positive regulation of proliferation, and the full original was not recovered. Preserve the historical TAS assertion as undecided rather than convert a proposal into a demonstrated activity. Supporting Evidence: |
| GO:0097193 intrinsic apoptotic signaling pathway | TAS PMID:8681378 cul-1 is required for cell cycle exit in C. elegans and iden... | UNDECIDED | Reason: The available PMID:8681378 abstract focuses on worm CUL-1 and does not resolve an intrinsic-apoptosis assay for human CUL3. Other CUL3 apoptotic mechanisms do not identify this specific branch or validate this source. Keep the historical TAS tuple undecided rather than declare misattribution from incomplete access. Supporting Evidence: |
Loading supporting content…
Download this section (compressed HTML)Q: Which CUL3 splice products assemble functional CRL3 complexes in specific tissues, and how do the N-terminal deletions alter adaptor affinity or substrate selection? Historical exon-deletion baits and disease-associated internal deletions are not equivalent to all three official products.
Q: Under which endogenous-protein, epitope-tag, antibody and nutrient-medium conditions does KLHL22 promote DEPDC5 turnover? The original report, later challenge and reply leave the substrate-specific mechanism unresolved.
Experiment: Compare purified full-length Q13618-1, Q13618-2 and Q13618-3 at matched protein concentrations for binding to selected BTB adaptors, RBX1 assembly and substrate-directed ubiquitination. Include the historical bait boundaries separately rather than treating them as full splice products.
Experiment: Test endogenous DEPDC5 turnover and mTORC1 outputs across matched DMEM and RPMI starvation/refeeding protocols, using validated antibodies, untagged controls and independent KLHL22 perturbations. Quantify any cleaved or selectively regulated DEPDC5 pool.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)