CUL3 is a cullin scaffold protein that forms CUL3-RBX1 cullin-RING E3 ubiquitin ligase complexes (CRL3). It bridges the RBX1/E2 ubiquitin-conjugating machinery with BTB/POZ-domain substrate-adaptor proteins (such as KEAP1, the KLHL family, KCTD family, SPOP, and RhoBTB proteins), enabling ubiquitination of adaptor-recruited substrates and, in many cases, their proteasome-mediated degradation. CRL3 activity is regulated by reversible neddylation/deneddylation of CUL3 and by the CAND1 and COP9 signalosome exchange machinery. Through its different substrate adaptors, CRL3 acts in the NRF2/KEAP1 oxidative-stress response, WNK-kinase-dependent renal electrolyte and blood-pressure homeostasis, mitotic progression and cytokinesis, cytoskeletal regulation, and many other substrate-specific processes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005634
nucleus
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CUL3 has nuclear localization in some contexts.
Reason: Nuclear localization is plausible for CUL3, but the review treats it as a broad compartment annotation rather than a pathway-specific function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0016567
protein ubiquitination
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0031625
ubiquitin protein ligase binding
|
IBA
GO_REF:0000033 |
MODIFY |
Summary: CUL3 is associated with ubiquitin ligase machinery, but the binding term is less informative than its scaffold activity.
Reason: The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes; ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex cellular-component annotation should be handled separately rather than used as an MF replacement.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0000209
protein polyubiquitination
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
Reason: Protein polyubiquitination is a proximal CRL3 output, while substrate-specific downstream effects should be curated separately.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
|
|
GO:0000278
mitotic cell cycle
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0000922
spindle pole
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CUL3 has nuclear localization in some contexts.
Reason: Nuclear localization is plausible for CUL3, but the review treats it as a broad compartment annotation rather than a pathway-specific function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CUL3 has cytoplasmic localization in some contexts.
Reason: Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should not be over-interpreted as a specific pathway output.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005794
Golgi apparatus
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: A pool of CUL3 localizes to the Golgi in the RhoBTB3-CUL3 adaptor context, so this localization is adaptor-specific rather than a core CUL3 cellular component.
Reason: Direct evidence (PMID:24145166) shows a RhoBTB3/CUL3/RBX1 ligase pool at the Golgi, so the Golgi annotation is retained as non-core and adaptor-specific, consistent with the IDA Golgi annotation for the same term.
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).
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0005813
centrosome
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005819
spindle
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0006915
apoptotic process
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0006950
response to stress
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0007165
signal transduction
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0010468
regulation of gene expression
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0031461
cullin-RING ubiquitin ligase complex
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031514
motile cilium
|
IEA
GO_REF:0000044 |
MARK AS OVER ANNOTATED |
Summary: This subcellular-location IEA annotation places CUL3 in the motile cilium, but this is not an established core CUL3 cellular component.
Reason: CUL3 has a role in ciliogenesis through ubiquitin-proteasome control of axoneme extension (PMID:25270598), but a stable motile cilium localization is not supported as a core CUL3 cellular component. The Falcon synthesis cautions that specific organellar/cytoskeletal localizations require source-level confirmation before retention.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0031625
ubiquitin protein ligase binding
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: CUL3 is associated with ubiquitin ligase machinery, but the binding term is less informative than its scaffold activity.
Reason: The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes; ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex cellular-component annotation should be handled separately rather than used as an MF replacement.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0098794
postsynapse
|
IEA
GO_REF:0000108 |
KEEP AS NON CORE |
Summary: This inter-ontology IEA annotation places CUL3 at the postsynapse, paired with the postsynaptic protein-catabolism process annotation, but it is not a core CUL3 location.
Reason: Postsynaptic localization is an adaptor/substrate-specific context (CRL3 contributes to postsynaptic protein turnover) rather than a core CUL3 cellular component. It may be valid in neuronal contexts but should not be promoted to a core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:18775313 UBXD7 binds multiple ubiquitin ligases and implicates p97 in... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:18850735 Characterization of the human COP9 signalosome complex using... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:19617556 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:20554658 Kelch-like homologue 9 mutation is associated with an early ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:20562859 Network organization of the human autophagy system. |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:21577200 Tumor-suppressor role for the SPOP ubiquitin ligase in signa... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:21828050 Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuate... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:21988832 Toward an understanding of the protein interaction network o... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:22466964 NEDD8 links cullin-RING ubiquitin ligase function to the p97... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:22542517 KBTBD13 interacts with Cullin 3 to form a functional ubiquit... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:22632832 Adaptor protein self-assembly drives the control of a cullin... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:23563313 CCDC22 deficiency in humans blunts activation of proinflamma... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:23665031 Disease-causing mutations in KLHL3 impair its effect on WNK4... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:25416956 A proteome-scale map of the human interactome network. |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:25619834 KLHL39 suppresses colon cancer metastasis by blocking KLHL20... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:27152988 The BTB domains of the potassium channel tetramerization dom... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:30190310 Dimerization quality control ensures neuronal development an... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:31515488 Extensive disruption of protein interactions by genetic vari... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:31652307 Kelch-like protein 5-mediated ubiquitination of lysine 183 p... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:32296183 A reference map of the human binary protein interactome. |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:37207277 Using brain cell-type-specific protein interactomes to inter... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:37788672 Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:38225382 Systematic discovery of protein interaction interfaces using... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:40205054 Multimodal cell maps as a foundation for structural and func... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0001822
kidney development
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0006954
inflammatory response
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0007229
integrin-mediated signaling pathway
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0010467
gene expression
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0016567
protein ubiquitination
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0017145
stem cell division
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0030163
protein catabolic process
|
IEA
GO_REF:0000107 |
MODIFY |
Summary: CUL3 participates in ubiquitin-dependent substrate catabolism rather than generic protein catabolism.
Reason: The more informative process term is ubiquitin-dependent or proteasome-mediated ubiquitin-dependent protein catabolism.
Proposed replacements:
proteasome-mediated ubiquitin-dependent protein catabolic process
ubiquitin-dependent protein catabolic process
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
|
|
GO:0030332
cyclin binding
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This ortholog-transferred IEA annotation reflects CRL3-mediated targeting of cyclin E for ubiquitination, but direct cyclin binding by CUL3 itself is not established.
Reason: Cyclin E is a CRL3 substrate (recruited via the RhoBTB3 adaptor at the Golgi; PMID:24145166 and PMID:10500095), but substrate recognition is mediated by the BTB adaptor rather than by direct CUL3 cyclin binding. Annotating CUL3 with cyclin binding over-attributes adaptor/substrate recognition to the scaffold.
Supporting Evidence:
PMID:24145166
RhoBTB3 is part of a CUL3–ubiquitin ligase complex on the Golgi that targets Cyclin E.
|
|
GO:0040016
embryonic cleavage
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0042802
identical protein binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: CUL3 self-association is plausible because CRL3 complexes adopt dimeric (2:2) architectures driven by BTB-adaptor dimerization, but this is a low-information binding term.
Reason: Structural studies show CRL3 complexes assemble as 2:2 dimers (a BTB-adaptor dimer recruiting two CUL3-RBX1 arms), so CUL3 molecules are present within a dimeric complex. However, identical protein binding is a generic term that does not capture the informative scaffold function and is retained only as non-core.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
structural/biochemical studies support **2:2 assemblies** (BTB dimer with two CUL3 arms) in CRL3 complexes
|
|
GO:0098978
glutamatergic synapse
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0140252
regulation protein catabolic process at postsynapse
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:22542517 KBTBD13 interacts with Cullin 3 to form a functional ubiquit... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:22632832 Adaptor protein self-assembly drives the control of a cullin... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:26399832 Cell-fate determination by ubiquitin-dependent regulation of... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:29249570 Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation, but this PMID is a review article and the IDA evidence code should be checked.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates. PMID:29249570 is a review article, so the process annotation can be retained but the IDA evidence code is suspicious and may represent an evidence-code mismatch with the accompanying NAS row.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:29249570 Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:31898230 CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases. |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
NAS
PMID:37628845 The Role of PIK3R1 in Metabolic Function and Insulin Sensiti... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
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 |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0005654
nucleoplasm
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: CUL3 has nucleoplasmic/nuclear localization in some contexts.
Reason: Nucleoplasmic localization is treated as a cautious cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0015630
microtubule cytoskeleton
|
IDA
GO_REF:0000052 |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005794
Golgi apparatus
|
IDA
PMID:24145166 Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation... |
KEEP AS NON CORE |
Summary: Direct evidence places a RhoBTB3-CUL3 ubiquitin ligase pool at the Golgi, but this is adaptor-specific rather than a core CUL3 location.
Reason: PMID:24145166 supports a Golgi-localized RhoBTB3/CUL3/RBX1 complex involved in Cyclin E regulation. Retain the direct IDA annotation as non-core and adaptor-specific rather than treating Golgi localization as a general CUL3 cellular component.
Supporting Evidence:
PMID:24145166
RhoBTB3 is part of a CUL3–ubiquitin ligase complex on the Golgi that targets Cyclin E.
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).
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0005515
protein binding
|
IPI
PMID:15107402 RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligas... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:35862218 ARMC5-CUL3 E3 ligase targets full-length SREBF in adrenocort... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:35687106 ARMC5 is part of an RPB1-specific ubiquitin ligase implicate... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:38225631 ARMC5 controls the degradation of most Pol II subunits, and ... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:39504960 Redundant pathways for removal of defective RNA polymerase I... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:39667934 CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:35687106 ARMC5 is part of an RPB1-specific ubiquitin ligase implicate... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:38225631 ARMC5 controls the degradation of most Pol II subunits, and ... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:39504960 Redundant pathways for removal of defective RNA polymerase I... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:39667934 CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0034599
cellular response to oxidative stress
|
IDA
PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:15601839 BTB protein Keap1 targets antioxidant transcription factor N... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0071230
cellular response to amino acid stimulus
|
IDA
PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:1904263
positive regulation of TORC1 signaling
|
IDA
PMID:29769719 KLHL22 activates amino-acid-dependent mTORC1 signalling to p... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0005737
cytoplasm
|
IDA
PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... |
ACCEPT |
Summary: CUL3 has cytoplasmic localization in some contexts.
Reason: Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should not be over-interpreted as a specific pathway output.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0070936
protein K48-linked ubiquitination
|
IDA
PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... |
ACCEPT |
Summary: CUL3 complexes can mediate K48-linked ubiquitination in specific substrate contexts.
Reason: K48-linked ubiquitination is a supported CRL3 output when the source evidence demonstrates degradative ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:27708159 Insulin resistance and diabetes caused by genetic or diet-in... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0160072
ubiquitin ligase complex scaffold activity
|
IDA
PMID:36394357 XAF1 prevents hyperproduction of type I interferon upon vira... |
ACCEPT |
Summary: CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
Reason: This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic machinery and BTB substrate adaptors rather than acting primarily as the catalytic transferase itself.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IMP
PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0070936
protein K48-linked ubiquitination
|
IDA
PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... |
ACCEPT |
Summary: CUL3 complexes can mediate K48-linked ubiquitination in specific substrate contexts.
Reason: K48-linked ubiquitination is a supported CRL3 output when the source evidence demonstrates degradative ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:25684205 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0005515
protein binding
|
IPI
PMID:28169274 Armc5 deletion causes developmental defects and compromises ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:19617556 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation ... |
MARK AS OVER ANNOTATED |
Summary: This localization is not established as a core CUL3 cellular component in this review.
Reason: The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus localization; membrane, Golgi, exosome, sperm flagellum, or other specific locations require source-level confirmation before retention.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0005515
protein binding
|
IPI
PMID:26906416 Characterization of the mammalian family of DCN-type NEDD8 E... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:24192928 Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylatio... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0000209
protein polyubiquitination
|
IDA
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
Reason: Protein polyubiquitination is a proximal CRL3 output, while substrate-specific downstream effects should be curated separately.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
|
|
GO:0005515
protein binding
|
IPI
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031625
ubiquitin protein ligase binding
|
IPI
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
MODIFY |
Summary: CUL3 is associated with ubiquitin ligase machinery, but the binding term is less informative than its scaffold activity.
Reason: The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes; ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex cellular-component annotation should be handled separately rather than used as an MF replacement.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0051865
protein autoubiquitination
|
IDA
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
UNDECIDED |
Summary: The source supports Cul3-dependent ubiquitination by assembled BTB-Cul3-Roc1 ligases, but it is unclear whether this row represents CUL3 autoubiquitination specifically.
Reason: CUL3 is the scaffold in the tested ligase assemblies, while ubiquitin transfer is mediated by the assembled E3 complex. Source-level review is needed before retaining protein autoubiquitination as a direct CUL3 process annotation.
Supporting Evidence:
PMID:14528312
Here, we show that Cul3, but not other cullins, binds directly to multiple BTB domains through a conserved amino-terminal domain.
PMID:14528312
In vitro, Cul3 promoted ubiquitination of Caenorhabditis elegans MEI-1, a katanin-like protein whose degradation requires the function of both Cul3 and BTB protein MEL-26.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IDA
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
MODIFY |
Summary: The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself is best represented as the scaffold.
Reason: For CUL3, ubiquitin ligase complex scaffold activity is the more accurate molecular function than a catalytic ubiquitin-protein transferase term.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0031208
POZ domain binding
|
IDA
PMID:14528312 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi... |
ACCEPT |
Summary: CUL3 binds BTB/POZ-domain substrate adaptors in CRL3 complexes.
Reason: POZ/BTB-domain adaptor binding is part of the core CRL3 scaffold architecture.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
|
|
GO:0000922
spindle pole
|
IDA
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005634
nucleus
|
IDA
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
ACCEPT |
Summary: CUL3 has nuclear localization in some contexts.
Reason: Nuclear localization is plausible for CUL3, but the review treats it as a broad compartment annotation rather than a pathway-specific function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005813
centrosome
|
IDA
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0072686
mitotic spindle
|
IDA
PMID:23213400 The CUL3-KLHL18 ligase regulates mitotic entry and ubiquityl... |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:29276004 Missense Variants in RHOBTB2 Cause a Developmental and Epile... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005737
cytoplasm
|
IDA
PMID:28395323 Defining the human sperm microtubulome: an integrated genomi... |
ACCEPT |
Summary: CUL3 has cytoplasmic localization in some contexts.
Reason: Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should not be over-interpreted as a specific pathway output.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0036126
sperm flagellum
|
IDA
PMID:28395323 Defining the human sperm microtubulome: an integrated genomi... |
MARK AS OVER ANNOTATED |
Summary: This localization is not established as a core CUL3 cellular component in this review.
Reason: The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus localization; membrane, Golgi, exosome, sperm flagellum, or other specific locations require source-level confirmation before retention.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0031398
positive regulation of protein ubiquitination
|
IGI
PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0031648
protein destabilization
|
IGI
PMID:24844779 Hypoxia-responsive microRNA-101 promotes angiogenesis via he... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:22748208 A homozygous mutation in KCTD7 links neuronal ceroid lipofus... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:23776465 Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear lo... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:26399832 Cell-fate determination by ubiquitin-dependent regulation of... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8932327 |
ACCEPT |
Summary: CUL3 can be represented in cytosolic CRL3 pathway contexts.
Reason: Cytosolic localization is compatible with CUL3 scaffold biology, although repetitive Reactome cytosol rows are left mostly pending for source-level review.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8952631 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8956040 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9712274 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9755505 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9755507 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9758090 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9759169 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9759172 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9766645 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9766656 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9766677 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9766687 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005112
Notch binding
|
IPI
PMID:25401743 KCTD10 is involved in the cardiovascular system and Notch si... |
MARK AS OVER ANNOTATED |
Summary: This annotation derives from a study of KCTD10 (a CUL3 BTB adaptor) in Notch signaling during embryonic development, but direct CUL3-Notch binding is not the core scaffold function.
Reason: PMID:25401743 links the CUL3-KCTD10 module to Notch signaling, but substrate recognition is mediated by the KCTD10 adaptor rather than direct CUL3-Notch binding. Notch binding is a substrate-contextual, low-information MF that over-attributes adaptor/substrate recognition to the CUL3 scaffold.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
IDA
PMID:25401743 KCTD10 is involved in the cardiovascular system and Notch si... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0005515
protein binding
|
IPI
PMID:26334369 Structural Insights into KCTD Protein Assembly and Cullin3 R... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
IDA
PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0071630
nuclear protein quality control by the ubiquitin-proteasome system
|
IDA
PMID:27561354 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnov... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0031145
anaphase-promoting complex-dependent catabolic process
|
IDA
PMID:10500095 Cullin-3 targets cyclin E for ubiquitination and controls S ... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:25270598 Ubiquitin-proteasome system controls ciliogenesis at the ini... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005515
protein binding
|
IPI
PMID:21778237 COMMD1 (copper metabolism MURR1 domain-containing protein 1)... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-5635854 |
ACCEPT |
Summary: CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
Reason: Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a cautious broad-compartment cellular component annotation consistent with the other accepted nucleus/nucleoplasm rows.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-5635855 |
ACCEPT |
Summary: CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
Reason: Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a cautious broad-compartment cellular component annotation consistent with the other accepted nucleus/nucleoplasm rows.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-HSA-5635856 |
ACCEPT |
Summary: CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
Reason: Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a cautious broad-compartment cellular component annotation consistent with the other accepted nucleus/nucleoplasm rows.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0007080
mitotic metaphase chromosome alignment
|
IMP
PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0007080
mitotic metaphase chromosome alignment
|
IMP
PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:24768539 K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ub... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0016020
membrane
|
HDA
PMID:19946888 Defining the membrane proteome of NK cells. |
MARK AS OVER ANNOTATED |
Summary: This localization is not established as a core CUL3 cellular component in this review.
Reason: The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus localization; membrane, Golgi, exosome, sperm flagellum, or other specific locations require source-level confirmation before retention.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0070062
extracellular exosome
|
HDA
PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... |
MARK AS OVER ANNOTATED |
Summary: This localization is not established as a core CUL3 cellular component in this review.
Reason: The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus localization; membrane, Golgi, exosome, sperm flagellum, or other specific locations require source-level confirmation before retention.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:19158078 Control of rapsyn stability by the CUL-3-containing E3 ligas... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:22578813 Translational homeostasis via the mRNA cap-binding protein, ... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:23453970 Impaired KLHL3-mediated ubiquitination of WNK4 causes human ... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:23576762 Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis v... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0005515
protein binding
|
IPI
PMID:18397884 Regulation of TIP60 by ATF2 modulates ATM activation. |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-1504190 |
ACCEPT |
Summary: CUL3 can be represented in cytosolic CRL3 pathway contexts.
Reason: Cytosolic localization is compatible with CUL3 scaffold biology, although repetitive Reactome cytosol rows are left mostly pending for source-level review.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-1504193 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-1504213 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-5658424 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8952630 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8955241 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8955289 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9018778 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9018787 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9706390 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9929484 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9929486 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9929490 |
ACCEPT |
Summary: CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
Reason: Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a broad-compartment cellular component annotation consistent with the other accepted cytosol/cytoplasm rows for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:23455478 Ubiquitylation-dependent localization of PLK1 in mitosis. |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0000209
protein polyubiquitination
|
IDA
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
Reason: Protein polyubiquitination is a proximal CRL3 output, while substrate-specific downstream effects should be curated separately.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
|
|
GO:0004842
ubiquitin-protein transferase activity
|
IDA
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
MODIFY |
Summary: The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself is best represented as the scaffold.
Reason: For CUL3, ubiquitin ligase complex scaffold activity is the more accurate molecular function than a catalytic ubiquitin-protein transferase term.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0005515
protein binding
|
IPI
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0031208
POZ domain binding
|
IDA
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
ACCEPT |
Summary: CUL3 binds BTB/POZ-domain substrate adaptors in CRL3 complexes.
Reason: POZ/BTB-domain adaptor binding is part of the core CRL3 scaffold architecture.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0032467
positive regulation of cytokinesis
|
IMP
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:19261606 The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is requi... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0004842
ubiquitin-protein transferase activity
|
IDA
PMID:15983046 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote... |
MODIFY |
Summary: The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself is best represented as the scaffold.
Reason: For CUL3, ubiquitin ligase complex scaffold activity is the more accurate molecular function than a catalytic ubiquitin-protein transferase term.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:15983046 Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0006513
protein monoubiquitination
|
IDA
PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... |
KEEP AS NON CORE |
Summary: Some CUL3-adaptor complexes mediate monoubiquitination rather than degradative polyubiquitination.
Reason: Protein monoubiquitination is a valid adaptor/substrate-specific CUL3 output, but it is not the main degradative CRL3 process summarized as core.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0007229
integrin-mediated signaling pathway
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0017145
stem cell division
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0040016
embryonic cleavage
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This automated or broad pathway annotation is downstream of CUL3-adaptor substrate biology rather than a core CUL3 function.
Reason: The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0048208
COPII vesicle coating
|
IMP
PMID:22358839 Ubiquitin-dependent regulation of COPII coat size and functi... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0005515
protein binding
|
IPI
PMID:18826954 SCCRO (DCUN1D1) is an essential component of the E3 complex ... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
GO:0004842
ubiquitin-protein transferase activity
|
IDA
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
MODIFY |
Summary: The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself is best represented as the scaffold.
Reason: For CUL3, ubiquitin ligase complex scaffold activity is the more accurate molecular function than a catalytic ubiquitin-protein transferase term.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0016477
cell migration
|
IMP
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0035024
negative regulation of Rho protein signal transduction
|
IMP
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043149
stress fiber assembly
|
IMP
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:19782033 Cullin mediates degradation of RhoA through evolutionarily c... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
|
IDA
PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate degradation.
Reason: Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
file:human/CUL3/CUL3-deep-research-falcon.md
not all CUL3-dependent ubiquitination is degradative
|
|
GO:0004842
ubiquitin-protein transferase activity
|
IDA
PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... |
MODIFY |
Summary: The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself is best represented as the scaffold.
Reason: For CUL3, ubiquitin ligase complex scaffold activity is the more accurate molecular function than a catalytic ubiquitin-protein transferase term.
Proposed replacements:
ubiquitin ligase complex scaffold activity
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase complex scaffold activity”** / **E3 ligase scaffold** rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold)
|
|
GO:0005827
polar microtubule
|
IDA
PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... |
KEEP AS NON CORE |
Summary: This cytoskeleton/centrosome/spindle localization is likely context-specific for CUL3-adaptor biology.
Reason: Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic or adaptor contexts but are not the core CUL3 location.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
**Membrane/centrosome/cytoskeleton claims require caution:**
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... |
ACCEPT |
Summary: CUL3-containing CRL3 complexes mediate protein ubiquitination.
Reason: Protein ubiquitination is the proximal biological process output of CUL3 scaffold function in CRL3 E3 ligase complexes.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:17543862 A Cul3-based E3 ligase removes Aurora B from mitotic chromos... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:19995937 The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midz... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0031463
Cul3-RING ubiquitin ligase complex
|
IDA
PMID:20389280 The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti... |
ACCEPT |
Summary: CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
Reason: CRL3 complex membership is a core cellular component annotation for CUL3.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate adaptor/receptor proteins** that recruit specific substrates.
file:human/CUL3/CUL3-deep-research-falcon.md
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors
|
|
GO:0005515
protein binding
|
IPI
PMID:18573101 KCTD5, a putative substrate adaptor for cullin3 ubiquitin li... |
MARK AS OVER ANNOTATED |
Summary: This is a generic protein binding annotation supported by a pairwise or high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor binding, RBX1, regulators) are captured by more specific terms.
Reason: Bare protein binding (GO:0005515) is low-information and should not be retained as a core CUL3 molecular function. CUL3's biologically meaningful interactions with BTB/POZ-domain substrate adaptors are already captured by POZ domain binding (GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity (GO:0160072). Many of these rows derive from large-scale interactome or affinity screens and capture adaptor, substrate, or non-specific partners rather than a distinct CUL3 function.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often **low-information** and may reflect experimental detection rather than biological specificity.
|
|
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 |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0008284
positive regulation of cell population proliferation
|
TAS
PMID:9733711 Cloning and expression analysis of a novel salicylate suppre... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
|
GO:0097193
intrinsic apoptotic signaling pathway
|
TAS
PMID:8681378 cul-1 is required for cell cycle exit in C. elegans and iden... |
KEEP AS NON CORE |
Summary: This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
Reason: The process can be retained as non-core where source evidence supports a specific CUL3-adaptor substrate context, but the core CUL3 function remains CRL3 scaffold-mediated ubiquitination.
Supporting Evidence:
file:human/CUL3/CUL3-deep-research-falcon.md
oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
|
Q: Which generic protein-binding rows correspond to direct CUL3-BTB adaptor, RBX1, substrate, or regulator interactions that should be converted to more informative terms?
Q: Which substrate-specific pathway and phenotype annotations have direct CUL3 scaffold-dependent evidence rather than adaptor/substrate or disease-context inference?
Q: Which annotations should distinguish CUL3's core scaffold activity from CRL3 regulation by neddylation, deneddylation, CSN, and CAND1-mediated adaptor exchange?
Experiment: Review CRL3 adaptor modules one at a time, separating CUL3 scaffold activity from adaptor-specific substrate recognition and downstream pathway outputs.
Experiment: Prioritize source-level review of membrane, Golgi, centrosome, spindle, cytoskeleton, and synaptic localization claims before retaining them as CUL3 cellular component annotations.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Concise GO annotation research for human CUL3 / UniProt Q13618 (cullin-3). Focus only on GO-relevant evidence: core molecular function as a cullin-RING E3 ubiquitin ligase scaffold / ubiquitin ligase complex scaffold activity; assembly of CRL3 complexes with RBX1 and BTB-domain substrate adaptors; roles in protein ubiquitination, protein polyubiquitination, proteasome-mediated ubiquitin-dependent protein catabolic process; neddylation/deneddylation regulation of CUL3 activity; cellular components including Cul3-RING ubiquitin ligase complex, cytoplasm/cytosol, nucleus, and any membrane/centrosome/cytoskeleton claims that need caution; substrate/adaptor examples such as KEAP1-NFE2L2/NRF2, KLHL3-WNK kinases, SPOP, KCTD proteins, cell-cycle or developmental substrates, and whether these should be core or non-core; distinguish direct CUL3 scaffold function from downstream phenotypes including cell cycle, development, oxidative stress response, neuronal phenotypes, blood pressure/electrolyte homeostasis, viral processes, and disease. Include caveats for generic protein binding or ubiquitin protein ligase binding annotations and for over-annotation from pathway membership or substrate phenotypes. Include PMID/DOI citations and keep under 1500 words.
This report summarizes evidence supporting core Gene Ontology (GO) annotations for human CUL3 as a cullin–RING E3 ubiquitin ligase scaffold (CRL3). Emphasis is on direct molecular function (MF), complex assembly/cellular component (CC), and proximal biological processes (BP) (ubiquitination and ubiquitin-dependent proteolysis), while downstream phenotypes/pathway roles (oxidative stress response, blood pressure, neurodevelopment, cancer, viral infection) are treated as non-core unless the evidence directly establishes CUL3’s mechanistic role.
CUL3 is the central scaffold of CRL3 ubiquitin ligases, bridging (i) a RING protein (RBX1) that recruits E2~ubiquitin and (ii) BTB-domain substrate adaptor/receptor proteins that recruit specific substrates. This architecture is described in recent mechanistic reviews and supported by primary structural work, including explicit CUL3–RBX1 and adaptor-bound complexes (jeong2023targetinge3ubiquitin pages 2-3, sharma2023insightsintothe pages 1-3, hu2024dynamicmoleculararchitecture pages 1-21).
Direct structural/biochemical evidence includes:
- Cryo-EM showing CRL3 assemblies containing CUL3 + RBX1 + BTB adaptor (e.g., KLHL22-based CRL3) and supporting the concept that dimerization of BTB adaptors yields a 2:2 stoichiometry (BTB dimer recruiting two CUL3–RBX1 arms) that supports ligase activity (wang2024aconservednterminal pages 1-2, wang2024aconservednterminal pages 7-8).
- KEAP1–CUL3 crystal structure evidence of a heterotetrameric 2:2 complex (KEAP1:CUL3) with quantitative binding (KD ~0.2 μM), reinforcing the scaffold/adaptor binding model (preprint) (adamson2023structuralandbiochemical pages 1-7).
GO MF term guidance: evidence best supports a CUL3 annotation consistent with “ubiquitin ligase complex scaffold activity” / E3 ligase scaffold rather than “ubiquitin-protein transferase activity” (which is catalytic and typically attributed to the E2/E3 catalytic machinery rather than the scaffold) (jeong2023targetinge3ubiquitin pages 2-3, wang2024aconservednterminal pages 1-2).
Recent structural work shows that CRL3s are multi-subunit complexes with physically resolved interfaces that underlie assembly.
- A May 2024 cryo-EM/biochemistry study on CRL3^KLHL22 identifies a conserved N-terminal motif in CUL3 that contributes to dimeric CRL3 assembly and E3 activity; deletion reduces adaptor binding and changes complex stoichiometry (wang2024aconservednterminal pages 7-8, wang2024aconservednterminal pages 1-2).
- Feb 2024 cryo-EM structural states of CRL3^KBTBD2 include substrate-engaged forms and regulatory complexes with the COP9 signalosome and CAND1, supporting CUL3’s role as a structural platform that coordinates catalytic and regulatory modules (hu2024dynamicmoleculararchitecture pages 1-21).
A 2024 Nature Structural & Molecular Biology study provides multiple cryo-EM reconstructions of CRL3^KBTBD2 including:
- A neddylated CRL3 form (CUL3~NEDD8),
- complexes with the COP9 signalosome (CSN) (including mutant CSN states), and
- a CUL3–RBX1–CAND1 complex.
These structures directly support GO-relevant assertions that CRL3 activity is coupled to neddylation/deneddylation and regulated by exchange factors such as CAND1 (hu2024dynamicmoleculararchitecture pages 1-21).
A 2023 Nature Chemical Biology study developed a conformation-specific probe recognizing NEDD8-linked active cullins and profiled activated CRL networks including CUL3-containing complexes (henneberg2023activitybasedprofilingof pages 1-2). The work includes experimental perturbations with MLN4924 (NAE inhibitor; blocks neddylation) and CSN5i-3 (blocks deneddylation), and explicitly detects NEDD8–CUL3 species by IP–MS (henneberg2023activitybasedprofilingof pages 6-6). This supports GO-relevant statements that (i) neddylation activates CRLs and (ii) active-state abundance is dynamically regulated.
A 2024 review in Signal Transduction and Targeted Therapy compiles recent structures that include CUL3–KLHL22–RBX1, CAND1–CUL3–RBX1, and KBTBD2–NEDD8–CUL3–RBX1–CSN assemblies (listed PDBs/EM structures), and emphasizes that CSN removes NEDD8 whereas CAND1 preferentially binds unneddylated cullins as a negative regulator/exchange factor (zhang2024proteinneddylationand pages 8-10). (Review-level evidence; use primarily to support general regulatory concepts rather than highly specific GO regulator terms.)
While not GO terms per se, applications inform which mechanistic aspects are robustly established.
Strongly supported (core):
- Ubiquitin ligase complex scaffold activity / E3 ubiquitin ligase scaffold — CUL3 is repeatedly defined and structurally demonstrated as a CRL scaffold bridging RBX1 and BTB adaptors, including detailed stoichiometry and interface determinants (wang2024aconservednterminal pages 1-2, adamson2023structuralandbiochemical pages 1-7, hu2024dynamicmoleculararchitecture pages 1-21).
Caution:
- Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein ligase binding” unless the evidence is specifically required for MF, because these terms are often low-information and may reflect experimental detection rather than biological specificity.
Strongly supported (core/proximal):
- Protein ubiquitination / protein polyubiquitination: Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural motifs (wang2024aconservednterminal pages 1-2), and CRL3^KCTD7 demonstrates CUL3-dependent ubiquitination of calpains (sengupta2023theubiquitinlikeproteins pages 4-5).
Proteasome-mediated ubiquitin-dependent protein catabolic process (supported, but adaptor/substrate-dependent):
- Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output (sharma2023insightsintothe pages 1-3). However, not all CUL3-dependent ubiquitination is degradative (see KCTD7/calpain below), so proteasome-related BP annotations should be supported by substrate degradation evidence rather than ubiquitination alone.
Critical caveat (avoid over-annotation):
- Non-degradative ubiquitination: the KCTD7–CUL3–RBX1 complex ubiquitinates calpains with atypical chain linkages (K6/K27/K29/K63) and regulates activity rather than proteasomal turnover; this supports “protein ubiquitination” but argues against automatically applying proteasome-mediated catabolism for all CUL3-dependent ubiquitination (sengupta2023theubiquitinlikeproteins pages 4-5).
- Pathway membership / phenotype-only evidence: oxidative stress response, blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream of CUL3-dependent substrate regulation. These should not be treated as core CUL3 BP terms without direct mechanistic evidence that CUL3’s scaffold activity is required in the specific pathway node being annotated.
Supported (core):
- Cul3-RING ubiquitin ligase complex / cullin-RING ubiquitin ligase complex: direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and BTB adaptors (hu2024dynamicmoleculararchitecture pages 1-21, wang2024aconservednterminal pages 1-2).
Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):
- A 2024 preprint reports differential tumor-context localization of CUL3 (cytoplasmic in one subtype; nuclear/perinuclear in another) and suggests nuclear engagement via interactions with RNA polymerase complexes in DNA damage contexts (pantazi2024ubiquitylationmediatedrnapiigenomic pages 100-104). Because this is preprint-level and partially inference-based, it supports a cautious note that CUL3 can be found in cytoplasmic and nuclear contexts but may not be sufficient alone for strong CC annotations.
Membrane/centrosome/cytoskeleton claims require caution:
- A 2024 structure paper on CRL3^KCTD5 describes compatibility with membrane-bound Gβγ in the reaction complex; this is substrate-contextual and does not justify annotating CUL3 broadly as a membrane component (jeong2023targetinge3ubiquitin pages 2-3).
- No strong direct evidence in the retrieved set supports centrosome or cytoskeleton localization as a general CC term for CUL3; references to kinetochores/mitosis are often substrate-contextual and may reflect downstream phenotype or adaptor targeting rather than stable CUL3 localization.
The table below summarizes adaptor modules and indicates which are core vs cautionary for CUL3 GO inference.
| Adaptor / CRL3 example | Example substrate or process context | What is directly evidenced about CUL3 | GO annotation relevance for human CUL3 | Caveats / evidence limits | Recent source (date; DOI/URL) |
|---|---|---|---|---|---|
| KEAP1–CUL3–RBX1 | NRF2 degradation under basal/non-oxidative conditions; KEAP1 recognizes NRF2 degrons | CUL3 N-terminus binds BTB/3-box adaptor KEAP1; CUL3 C-terminus assembles with RBX1; KEAP1:CUL3 forms a heterotetrameric 2:2 assembly; neddylation of CUL3 CTD promotes active ubiquitin-transfer geometry (adamson2023structuralandbiochemical pages 1-7, jeong2023targetinge3ubiquitin pages 2-3) | Core for MF/CC: ubiquitin ligase complex scaffold activity; Cul3-RING ubiquitin ligase complex. Process: protein ubiquitination / polyubiquitination; proteasome-mediated ubiquitin-dependent catabolic process can be supported when tied to NRF2 degradation, but keep focus on scaffold role (adamson2023structuralandbiochemical pages 1-7, sharma2023insightsintothe pages 1-3) | Preprint for detailed KEAP1-CUL3 structure; KEAP1/NRF2 oxidative-stress phenotypes are downstream and should not be over-transferred to CUL3 as core BP beyond ubiquitination/catabolism (adamson2023structuralandbiochemical pages 1-7, sharma2023insightsintothe pages 1-3) | Feb 2023, doi:10.1101/2023.02.15.528651, https://doi.org/10.1101/2023.02.15.528651; Oct 2023, doi:10.1186/s12964-023-01269-z, https://doi.org/10.1186/s12964-023-01269-z |
| KLHL22–CUL3–RBX1 | Polyubiquitination of reported substrates such as PLK1/PD1/DEPDC5; model for CRL3 dimeric activity | Cryo-EM/biochemistry show CUL3 is the scaffold of CRL3; BTB dimer recruits two CUL3-RBX1 arms (2:2); conserved CUL3 N-terminal motif contributes to dimeric assembly and E3 activity; deletion impairs binding and ubiquitination activity (wang2024aconservednterminal pages 1-2, wang2024aconservednterminal pages 7-8) | Core for MF/CC: scaffold activity; Cul3-RING ubiquitin ligase complex assembly. Core/moderate for BP: protein polyubiquitination (directly assayed in CRL3 context) (wang2024aconservednterminal pages 1-2) | Substrate-specific phenotypes (mitosis, autophagy, signaling) should be treated as non-core for CUL3 unless directly evidenced in human CUL3 context; avoid over-annotation from adaptor pathway membership (wang2024aconservednterminal pages 1-2) | May 2024, doi:10.1038/s41467-024-48045-2, https://doi.org/10.1038/s41467-024-48045-2 |
| KLHL12–CUL3 | SEC31 monoubiquitylation; large COPII structure formation / procollagen export | Review/primary evidence states CUL3 is CRL3 scaffold; CRL3^KLHL12 ubiquitylates SEC31; CUL3 neddylation activates CRL3 via conformational change near RBX1/E2-Ub positioning (moretti2023klhl12canform pages 1-2) | Core for MF: scaffold in ubiquitin ligase complex. Caution for BP: “protein ubiquitination” supported; do not default to proteasome-mediated catabolism here because SEC31 example is monoubiquitylation and collagen effects may involve lysosomal handling (moretti2023klhl12canform pages 1-2) | Not a strong basis for proteasome-related GO on CUL3 from this module alone; COPII/ER-exit-site or membrane-trafficking claims are adaptor/substrate-contextual, not core CUL3 location/function (moretti2023klhl12canform pages 1-2) | Mar 2023, doi:10.1091/mbc.e22-08-0383, https://doi.org/10.1091/mbc.e22-08-0383 |
| KBTBD2–CUL3–RBX1 | p85α / PI3K regulatory subunit recruitment; substrate-engaged CRL3 architecture | High-resolution cryo-EM captures CRL3^KBTBD2, substrate-bound complexes, neddylated CUL3, CUL3–RBX1–CAND1, and CUL3 complexes with COP9 signalosome (CSN), providing direct evidence for scaffold assembly plus neddylation/deneddylation and exchange regulation (hu2024dynamicmoleculararchitecture pages 1-21) | Core for MF/CC/BP: ubiquitin ligase complex scaffold activity; Cul3-RING ubiquitin ligase complex; regulation of CRL3 activity by neddylation/deneddylation can support regulation-related annotation if term selection is careful (hu2024dynamicmoleculararchitecture pages 1-21) | Best recent structural support for regulation, but substrate-specific signaling outputs should remain non-core; no direct subcellular localization claim should be expanded beyond complex membership from this study alone (hu2024dynamicmoleculararchitecture pages 1-21) | Feb 2024, doi:10.1038/s41594-023-01182-6, https://doi.org/10.1038/s41594-023-01182-6 |
| KCTD5–CUL3–RBX1 | Gβγ ubiquitylation; membrane-proximal signaling context | Pentameric KCTD5/CUL3/Gβγ complex architecture shows CUL3 in BTB/cullin core CRL3; CUL3-based complex positions substrate for ubiquitin transfer; reaction complex is described as compatible with membrane-bound Gβγ (jeong2023targetinge3ubiquitin pages 2-3) | Core for scaffold/ubiquitination. Caution for localization: membrane compatibility of a specific CRL3^KCTD5 reaction complex does not justify generic membrane annotation for CUL3 (jeong2023targetinge3ubiquitin pages 2-3) | Membrane association is context-specific and substrate-dependent; avoid annotating CUL3 broadly to membrane based on one adaptor/substrate system (jeong2023targetinge3ubiquitin pages 2-3) | Apr 2024, doi:10.1073/pnas.2315018121, https://doi.org/10.1073/pnas.2315018121 |
| KCTD7–CUL3–RBX1 | Calpain regulation by non-degradative ubiquitination | Primary study shows KCTD7 works in complex with CUL3 and RBX1 to ubiquitinate calpains with non-K48 linkage patterns and regulate activity rather than degradation (sengupta2023theubiquitinlikeproteins pages 4-5) | Core for “protein ubiquitination.” Caution/non-core for proteasome-mediated catabolic process, because this is explicitly non-degradative ubiquitination (sengupta2023theubiquitinlikeproteins pages 4-5) | Do not infer protein catabolism/proteasome process from all CUL3 substrates; also avoid inferring neuronal disease phenotypes as direct CUL3 GO BP terms (sengupta2023theubiquitinlikeproteins pages 4-5) | Mar 2023, doi:10.1038/s41421-023-00533-3, https://doi.org/10.1038/s41421-023-00533-3 |
| SPOP–CUL3–RBX1 | Broad substrate adaptor example; cancer- and virus-related substrate studies discussed in reviews | Reviews describe SPOP as a BTB adaptor of the CUL3/RBX1 complex; BACK/BTB adaptors and SPOP higher-order assemblies can enhance CRL3 activity (jeong2023targetinge3ubiquitin pages 2-3) | Useful as supporting example, but usually non-core for CUL3 annotation unless citing direct human CUL3 biochemical evidence in the same experiment. Safe use: adaptor repertoire supporting CRL3 assembly concept (jeong2023targetinge3ubiquitin pages 2-3) | Many SPOP papers focus on adaptor phenotypes or disease substrates, not direct CUL3 scaffold biochemistry; avoid over-annotation from cancer/viral phenotypes to CUL3 BP terms (jeong2023targetinge3ubiquitin pages 2-3) | Oct 2023, doi:10.1038/s12276-023-01087-w, https://doi.org/10.1038/s12276-023-01087-w |
| CUL3 regulation by NEDD8 / CSN / CAND1 | Activation/inactivation cycle of CRL3 complexes | NEDD8 conjugation activates cullin-RING ligases; recent work measures NEDD8-CUL3 and perturbation by MLN4924 or deneddylation inhibitor CSN5i-3; reviews state CSN removes NEDD8; structural studies capture CUL3–RBX1–CAND1 and CUL3~NEDD8–CSN complexes (henneberg2023activitybasedprofilingof pages 1-2, henneberg2023activitybasedprofilingof pages 6-6, sharma2023insightsintothe pages 1-3, zhang2024proteinneddylationand pages 8-10, hu2024dynamicmoleculararchitecture pages 1-21) | Core regulatory context for CRL3 activity. Good support for annotations tied to cullin deneddylation/neddylation regulation or regulation of ubiquitin ligase activity, if the GO term matches the evidence scope (zhang2024proteinneddylationand pages 8-10, hu2024dynamicmoleculararchitecture pages 1-21, henneberg2023activitybasedprofilingof pages 1-2, sharma2023insightsintothe pages 1-3) | Some evidence is general-to-cullin or review-based; use care in assigning highly specific regulator terms unless direct human CUL3 experimental support is cited. No direct support here for broad cellular-component claims beyond CRL3 complex itself (zhang2024proteinneddylationand pages 8-10, henneberg2023activitybasedprofilingof pages 1-2, sharma2023insightsintothe pages 1-3) | Aug 2023, doi:10.1038/s41589-023-01392-5, https://doi.org/10.1038/s41589-023-01392-5; Apr 2024, doi:10.1038/s41392-024-01800-9, https://doi.org/10.1038/s41392-024-01800-9; Feb 2024, doi:10.1038/s41594-023-01182-6, https://doi.org/10.1038/s41594-023-01182-6 |
Table: This table summarizes direct GO-relevant evidence for human CUL3 across key CRL3 adaptor systems, highlighting what supports core scaffold and ubiquitination annotations versus what should be treated cautiously as adaptor-specific, non-degradative, or phenotype-driven.
References
(jeong2023targetinge3ubiquitin pages 2-3): Yelin Jeong, Ah-Reum Oh, Young Hoon Jung, HyunJoon Gi, Young Un Kim, and KyeongJin Kim. Targeting e3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases. Experimental & Molecular Medicine, 55:2097-2104, Oct 2023. URL: https://doi.org/10.1038/s12276-023-01087-w, doi:10.1038/s12276-023-01087-w. This article has 56 citations and is from a peer-reviewed journal.
(sharma2023insightsintothe pages 1-3): Prashant Sharma and Harish E. Chatrathi. Insights into the diverse mechanisms and effects of variant cul3-induced familial hyperkalemic hypertension. Cell Communication and Signaling : CCS, Oct 2023. URL: https://doi.org/10.1186/s12964-023-01269-z, doi:10.1186/s12964-023-01269-z. This article has 6 citations.
(hu2024dynamicmoleculararchitecture pages 1-21): Yuxia Hu, Zhao Zhang, Qiyu Mao, Xiang Zhang, Aihua Hao, Yu Xun, Yeda Wang, Lin Han, Wuqiang Zhan, Qianying Liu, Yue Yin, Chao Peng, Eva Marie Y. Moresco, Zhenguo Chen, Bruce Beutler, and Lei Sun. Dynamic molecular architecture and substrate recruitment of cullin3-ring e3 ligase crl3kbtbd2. Nature structural & molecular biology, 31:336-350, Feb 2024. URL: https://doi.org/10.1038/s41594-023-01182-6, doi:10.1038/s41594-023-01182-6. This article has 21 citations and is from a highest quality peer-reviewed journal.
(wang2024aconservednterminal pages 1-2): Weize Wang, Ling Liang, Zonglin Dai, Peng Zuo, Shang Yu, Yishuo Lu, Dian Ding, Hongyi Chen, Hui Shan, Yan Jin, Youdong Mao, and Yuxin Yin. A conserved n-terminal motif of cul3 contributes to assembly and e3 ligase activity of crl3klhl22. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48045-2, doi:10.1038/s41467-024-48045-2. This article has 16 citations and is from a highest quality peer-reviewed journal.
(wang2024aconservednterminal pages 7-8): Weize Wang, Ling Liang, Zonglin Dai, Peng Zuo, Shang Yu, Yishuo Lu, Dian Ding, Hongyi Chen, Hui Shan, Yan Jin, Youdong Mao, and Yuxin Yin. A conserved n-terminal motif of cul3 contributes to assembly and e3 ligase activity of crl3klhl22. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48045-2, doi:10.1038/s41467-024-48045-2. This article has 16 citations and is from a highest quality peer-reviewed journal.
(adamson2023structuralandbiochemical pages 1-7): Roslin J Adamson, N Connor Payne, Sergio G. Bartual, Ralph Mazitschek, and Alex N Bullock. Structural and biochemical characterization establishes a detailed understanding of keap1-cul3 complex assembly. bioRxiv, Feb 2023. URL: https://doi.org/10.1101/2023.02.15.528651, doi:10.1101/2023.02.15.528651. This article has 34 citations.
(henneberg2023activitybasedprofilingof pages 1-2): Lukas T. Henneberg, Jaspal Singh, David M. Duda, Kheewoong Baek, David Yanishevski, Peter J. Murray, Matthias Mann, Sachdev S. Sidhu, and Brenda A. Schulman. Activity-based profiling of cullin–ring e3 networks by conformation-specific probes. Nature Chemical Biology, 19:1513-1523, Aug 2023. URL: https://doi.org/10.1038/s41589-023-01392-5, doi:10.1038/s41589-023-01392-5. This article has 32 citations and is from a highest quality peer-reviewed journal.
(henneberg2023activitybasedprofilingof pages 6-6): Lukas T. Henneberg, Jaspal Singh, David M. Duda, Kheewoong Baek, David Yanishevski, Peter J. Murray, Matthias Mann, Sachdev S. Sidhu, and Brenda A. Schulman. Activity-based profiling of cullin–ring e3 networks by conformation-specific probes. Nature Chemical Biology, 19:1513-1523, Aug 2023. URL: https://doi.org/10.1038/s41589-023-01392-5, doi:10.1038/s41589-023-01392-5. This article has 32 citations and is from a highest quality peer-reviewed journal.
(zhang2024proteinneddylationand pages 8-10): Shizhen Zhang, Qing Yu, Zhijian Li, Yongchao Zhao, and Yi Sun. Protein neddylation and its role in health and diseases. Signal Transduction and Targeted Therapy, Apr 2024. URL: https://doi.org/10.1038/s41392-024-01800-9, doi:10.1038/s41392-024-01800-9. This article has 148 citations and is from a peer-reviewed journal.
(gu2024cullin3ring pages 1-2): Lijie Gu, Yanhong Du, Jianglei Chen, Mohammad Nazmul Hasan, Yung Dai Clayton, David J. Matye, Jacob E. Friedman, and Tiangang Li. Cullin 3 ring e3 ligase inactivation causes nrf2-dependent nadh reductive stress, hepatic lipodystrophy, and systemic insulin resistance. Proceedings of the National Academy of Sciences of the United States of America, Apr 2024. URL: https://doi.org/10.1073/pnas.2320934121, doi:10.1073/pnas.2320934121. This article has 21 citations and is from a highest quality peer-reviewed journal.
(sengupta2023theubiquitinlikeproteins pages 4-5): Swarnab Sengupta and Elah Pick. The ubiquitin-like proteins of saccharomyces cerevisiae. Biomolecules, 13:734, Apr 2023. URL: https://doi.org/10.3390/biom13050734, doi:10.3390/biom13050734. This article has 4 citations.
(pantazi2024ubiquitylationmediatedrnapiigenomic pages 100-104): Vasiliki Pantazi. Ubiquitylation-mediated rnapii genomic eviction in response to dna dsbs. ArXiv, 2024. URL: https://doi.org/10.14232/phd.12363, doi:10.14232/phd.12363. This article has 0 citations.
(moretti2023klhl12canform pages 1-2): Tamara Moretti, Kyungho Kim, Astha Tuladhar, and Jinoh Kim. Klhl12 can form large copii structures in the absence of cul3 neddylation. Molecular Biology of the Cell, Mar 2023. URL: https://doi.org/10.1091/mbc.e22-08-0383, doi:10.1091/mbc.e22-08-0383. This article has 11 citations and is from a domain leading peer-reviewed journal.
Initial Falcon pass, 2026-05-12. CUL3 started as a fully pending review with
228 annotations. I kept this pass centered on the conserved CRL3 scaffold
function and left most generic protein-binding and substrate-specific rows for
later source-level review.
Core molecular function: CUL3 is the scaffold of cullin-RING E3 ligase
complexes. Falcon states that CUL3 bridges RBX1/E2 ubiquitin-conjugating
machinery with BTB-domain substrate adaptors
[file:human/CUL3/CUL3-deep-research-falcon.md "CUL3 is the central
scaffold of CRL3 ubiquitin ligases, bridging (i) a RING protein (RBX1)
that recruits E2~ubiquitin and (ii) BTB-domain substrate adaptor/receptor
proteins that recruit specific substrates."]. I accepted ubiquitin ligase
complex scaffold activity and Cul3-RING ubiquitin ligase complex rows as the
core axis.
Core process: protein ubiquitination, polyubiquitination, and
proteasome-mediated ubiquitin-dependent catabolism are proximal outputs of many
CRL3 complexes [file:human/CUL3/CUL3-deep-research-falcon.md "Proteasomal
targeting is a canonical outcome for many CRLs, and reviews explicitly describe
substrate ubiquitination “for proteasomal degradation” as a CRL3 output"]. I
accepted well-supported ubiquitination and catabolic-process rows, but kept the
caveat that not every CUL3 ubiquitination event is degradative.
Molecular-function specificity: Falcon cautions that CUL3 is best represented
as the scaffold rather than the catalytic ubiquitin transferase
[file:human/CUL3/CUL3-deep-research-falcon.md "evidence best supports a CUL3
annotation consistent with “ubiquitin ligase complex scaffold activity” /
E3 ligase scaffold rather than “ubiquitin-protein transferase activity”
(which is catalytic and typically attributed to the E2/E3 catalytic machinery
rather than the scaffold)"]. I therefore modified ubiquitin-protein transferase
and ubiquitin protein ligase activity rows to the scaffold term.
Non-core contexts: many CUL3 annotations reflect the substrate/adaptor being
studied: KEAP1/NRF2 oxidative stress, KLHL3/WNK ion transport, KLHL12/COPII,
KBTBD/KCTD complexes, mitotic substrates, neuronal phenotypes, viral processes,
and disease models. Falcon warns that broad phenotypes should not be promoted
to core CUL3 functions without direct mechanistic evidence
[file:human/CUL3/CUL3-deep-research-falcon.md "oxidative stress response,
blood pressure/electrolyte phenotypes, neurodevelopmental phenotypes, or
cancer-associated phenotypes can be downstream of CUL3-dependent substrate
regulation. These should not be treated as core CUL3 BP terms without direct
mechanistic evidence that CUL3’s scaffold activity is required in the specific
pathway node being annotated."].
Localization: CUL3 complex membership is core. I accepted a few broad
cytoplasm/cytosol/nuclear rows, but Falcon notes that specific membrane,
centrosome, cytoskeleton, and other locations require caution
[file:human/CUL3/CUL3-deep-research-falcon.md "Membrane/centrosome/cytoskeleton
claims require caution:"]. Most highly specific or repetitive localization
rows remain pending unless a direct source was already strong enough for a
non-core decision.
Left for later: generic protein-binding rows should be triaged by partner
(BTB/POZ adaptor, RBX1, substrate, CSN/CAND1 regulator, or nonspecific
interaction). Substrate-specific phenotype rows should be reviewed one adaptor
module at a time rather than treated as core CUL3 biology.
id: Q13618
gene_symbol: CUL3
product_type: PROTEIN
status: INITIALIZED
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
CUL3 is a cullin scaffold protein that forms CUL3-RBX1 cullin-RING E3 ubiquitin
ligase complexes (CRL3). It bridges the RBX1/E2 ubiquitin-conjugating machinery
with BTB/POZ-domain substrate-adaptor proteins (such as KEAP1, the KLHL family,
KCTD family, SPOP, and RhoBTB proteins), enabling ubiquitination of adaptor-recruited
substrates and, in many cases, their proteasome-mediated degradation. CRL3 activity
is regulated by reversible neddylation/deneddylation of CUL3 and by the CAND1 and COP9
signalosome exchange machinery. Through its different substrate adaptors, CRL3 acts in
the NRF2/KEAP1 oxidative-stress response, WNK-kinase-dependent renal electrolyte and
blood-pressure homeostasis, mitotic progression and cytokinesis, cytoskeletal
regulation, and many other substrate-specific processes.
alternative_products:
- name: 1 (Cul-3 Long)
id: Q13618-1
- name: '2'
id: Q13618-2
sequence_note: VSP_008824
- name: 3 (Cul-3 Short)
id: Q13618-3
sequence_note: VSP_008825
existing_annotations:
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3 has nuclear localization in some contexts.
action: ACCEPT
reason: >-
Nuclear localization is plausible for CUL3, but the review treats it as a broad
compartment annotation rather than a pathway-specific function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0031625
label: ubiquitin protein ligase binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3 is associated with ubiquitin ligase machinery, but the binding term is less
informative than its scaffold activity.
action: MODIFY
reason: >-
The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes;
ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex
cellular-component annotation should be handled separately rather than used as an
MF replacement.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0000209
label: protein polyubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
action: ACCEPT
reason: >-
Protein polyubiquitination is a proximal CRL3 output, while substrate-specific
downstream effects should be curated separately.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- term:
id: GO:0000278
label: mitotic cell cycle
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0000922
label: spindle pole
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
CUL3 has nuclear localization in some contexts.
action: ACCEPT
reason: >-
Nuclear localization is plausible for CUL3, but the review treats it as a broad
compartment annotation rather than a pathway-specific function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
CUL3 has cytoplasmic localization in some contexts.
action: ACCEPT
reason: >-
Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should
not be over-interpreted as a specific pathway output.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
A pool of CUL3 localizes to the Golgi in the RhoBTB3-CUL3 adaptor context, so this
localization is adaptor-specific rather than a core CUL3 cellular component.
action: KEEP_AS_NON_CORE
reason: >-
Direct evidence (PMID:24145166) shows a RhoBTB3/CUL3/RBX1 ligase pool at the Golgi,
so the Golgi annotation is retained as non-core and adaptor-specific, consistent
with the IDA Golgi annotation for the same term.
supported_by:
- reference_id: PMID:24145166
supporting_text: >-
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).
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0005813
label: centrosome
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005819
label: spindle
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0006915
label: apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0006950
label: response to stress
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0007165
label: signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0010468
label: regulation of gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0031461
label: cullin-RING ubiquitin ligase complex
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031514
label: motile cilium
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: >-
This subcellular-location IEA annotation places CUL3 in the motile cilium, but
this is not an established core CUL3 cellular component.
action: MARK_AS_OVER_ANNOTATED
reason: >-
CUL3 has a role in ciliogenesis through ubiquitin-proteasome control of axoneme
extension (PMID:25270598), but a stable motile cilium localization is not supported
as a core CUL3 cellular component. The Falcon synthesis cautions that specific
organellar/cytoskeletal localizations require source-level confirmation before
retention.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0031625
label: ubiquitin protein ligase binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
CUL3 is associated with ubiquitin ligase machinery, but the binding term is less
informative than its scaffold activity.
action: MODIFY
reason: >-
The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes;
ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex
cellular-component annotation should be handled separately rather than used as an
MF replacement.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0098794
label: postsynapse
evidence_type: IEA
original_reference_id: GO_REF:0000108
review:
summary: >-
This inter-ontology IEA annotation places CUL3 at the postsynapse, paired with the
postsynaptic protein-catabolism process annotation, but it is not a core CUL3
location.
action: KEEP_AS_NON_CORE
reason: >-
Postsynaptic localization is an adaptor/substrate-specific context (CRL3 contributes
to postsynaptic protein turnover) rather than a core CUL3 cellular component. It may
be valid in neuronal contexts but should not be promoted to a core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12609982
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17543862
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18775313
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18850735
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19427028
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19615732
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19617556
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20389280
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20554658
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20562859
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21145461
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21577200
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21828050
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21988832
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22466964
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22542517
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22632832
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22939624
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23563313
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23665031
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25502805
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25619834
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25684205
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26949739
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27152988
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:30190310
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31515488
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31652307
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32814053
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:34591642
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35512704
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:37207277
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:37788672
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:38225382
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:40205054
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0001822
label: kidney development
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0006954
label: inflammatory response
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0007229
label: integrin-mediated signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0010467
label: gene expression
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0017145
label: stem cell division
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0030163
label: protein catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
CUL3 participates in ubiquitin-dependent substrate catabolism rather than generic
protein catabolism.
action: MODIFY
reason: >-
The more informative process term is ubiquitin-dependent or proteasome-mediated
ubiquitin-dependent protein catabolism.
proposed_replacement_terms:
- id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
- id: GO:0006511
label: ubiquitin-dependent protein catabolic process
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- term:
id: GO:0030332
label: cyclin binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This ortholog-transferred IEA annotation reflects CRL3-mediated targeting of cyclin
E for ubiquitination, but direct cyclin binding by CUL3 itself is not established.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Cyclin E is a CRL3 substrate (recruited via the RhoBTB3 adaptor at the Golgi;
PMID:24145166 and PMID:10500095), but substrate recognition is mediated by the
BTB adaptor rather than by direct CUL3 cyclin binding. Annotating CUL3 with cyclin
binding over-attributes adaptor/substrate recognition to the scaffold.
supported_by:
- reference_id: PMID:24145166
supporting_text: >-
RhoBTB3 is part of a CUL3–ubiquitin ligase complex on the Golgi that targets
Cyclin E.
- term:
id: GO:0040016
label: embryonic cleavage
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
CUL3 self-association is plausible because CRL3 complexes adopt dimeric (2:2)
architectures driven by BTB-adaptor dimerization, but this is a low-information
binding term.
action: KEEP_AS_NON_CORE
reason: >-
Structural studies show CRL3 complexes assemble as 2:2 dimers (a BTB-adaptor dimer
recruiting two CUL3-RBX1 arms), so CUL3 molecules are present within a dimeric
complex. However, identical protein binding is a generic term that does not capture
the informative scaffold function and is retained only as non-core.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
structural/biochemical studies support **2:2 assemblies** (BTB dimer with two CUL3
arms) in CRL3 complexes
- term:
id: GO:0098978
label: glutamatergic synapse
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0140252
label: regulation protein catabolic process at postsynapse
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:22542517
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:22632832
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:25684205
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:26399832
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:29249570
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation, but this PMID is a review article and the IDA evidence code should
be checked.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates. PMID:29249570 is a review article, so the
process annotation can be retained but the IDA evidence code is suspicious and may
represent an evidence-code mismatch with the accompanying NAS row.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:29249570
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:31898230
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: NAS
original_reference_id: PMID:37628845
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:37788672
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:19782033
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: >-
CUL3 has nucleoplasmic/nuclear localization in some contexts.
action: ACCEPT
reason: >-
Nucleoplasmic localization is treated as a cautious cellular component annotation
for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0015630
label: microtubule cytoskeleton
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IDA
original_reference_id: PMID:24145166
review:
summary: >-
Direct evidence places a RhoBTB3-CUL3 ubiquitin ligase pool at the Golgi, but
this is adaptor-specific rather than a core CUL3 location.
action: KEEP_AS_NON_CORE
reason: >-
PMID:24145166 supports a Golgi-localized RhoBTB3/CUL3/RBX1 complex involved in
Cyclin E regulation. Retain the direct IDA annotation as non-core and
adaptor-specific rather than treating Golgi localization as a general CUL3
cellular component.
supported_by:
- reference_id: PMID:24145166
supporting_text: >-
RhoBTB3 is part of a CUL3–ubiquitin ligase complex on the Golgi that targets
Cyclin E.
- reference_id: PMID:24145166
supporting_text: >-
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).
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:29769719
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:15601839
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15107402
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:23453970
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:35862218
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:35687106
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:38225631
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:39504960
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:39667934
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:35687106
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:38225631
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:39504960
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:39667934
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0034599
label: cellular response to oxidative stress
evidence_type: IDA
original_reference_id: PMID:15601839
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:15601839
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0071230
label: cellular response to amino acid stimulus
evidence_type: IDA
original_reference_id: PMID:29769719
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:29769719
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:1904263
label: positive regulation of TORC1 signaling
evidence_type: IDA
original_reference_id: PMID:29769719
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:23453970
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:27708159
review:
summary: >-
CUL3 has cytoplasmic localization in some contexts.
action: ACCEPT
reason: >-
Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should
not be over-interpreted as a specific pathway output.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0070936
label: protein K48-linked ubiquitination
evidence_type: IDA
original_reference_id: PMID:27708159
review:
summary: >-
CUL3 complexes can mediate K48-linked ubiquitination in specific substrate
contexts.
action: ACCEPT
reason: >-
K48-linked ubiquitination is a supported CRL3 output when the source evidence
demonstrates degradative ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:27708159
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:1900076
label: regulation of cellular response to insulin stimulus
evidence_type: IDA
original_reference_id: PMID:27708159
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0032480
label: negative regulation of type I interferon production
evidence_type: IDA
original_reference_id: PMID:36394357
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
evidence_type: IDA
original_reference_id: PMID:36394357
review:
summary: >-
CUL3 provides ubiquitin ligase complex scaffold activity in CRL3 complexes.
action: ACCEPT
reason: >-
This is the core molecular function of CUL3: it scaffolds RBX1/E2 catalytic
machinery and BTB substrate adaptors rather than acting primarily as the catalytic
transferase itself.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IMP
original_reference_id: PMID:25684205
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0070936
label: protein K48-linked ubiquitination
evidence_type: IDA
original_reference_id: PMID:25684205
review:
summary: >-
CUL3 complexes can mediate K48-linked ubiquitination in specific substrate
contexts.
action: ACCEPT
reason: >-
K48-linked ubiquitination is a supported CRL3 output when the source evidence
demonstrates degradative ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:25684205
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:28169274
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:19617556
review:
summary: >-
This localization is not established as a core CUL3 cellular component in this
review.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus
localization; membrane, Golgi, exosome, sperm flagellum, or other specific
locations require source-level confirmation before retention.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26906416
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24192928
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0000209
label: protein polyubiquitination
evidence_type: IDA
original_reference_id: PMID:14528312
review:
summary: >-
CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
action: ACCEPT
reason: >-
Protein polyubiquitination is a proximal CRL3 output, while substrate-specific
downstream effects should be curated separately.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:14528312
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:14528312
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031625
label: ubiquitin protein ligase binding
evidence_type: IPI
original_reference_id: PMID:14528312
review:
summary: >-
CUL3 is associated with ubiquitin ligase machinery, but the binding term is less
informative than its scaffold activity.
action: MODIFY
reason: >-
The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes;
ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex
cellular-component annotation should be handled separately rather than used as an
MF replacement.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0051865
label: protein autoubiquitination
evidence_type: IDA
original_reference_id: PMID:14528312
review:
summary: >-
The source supports Cul3-dependent ubiquitination by assembled BTB-Cul3-Roc1
ligases, but it is unclear whether this row represents CUL3 autoubiquitination
specifically.
action: UNDECIDED
reason: >-
CUL3 is the scaffold in the tested ligase assemblies, while ubiquitin transfer is
mediated by the assembled E3 complex. Source-level review is needed before
retaining protein autoubiquitination as a direct CUL3 process annotation.
supported_by:
- reference_id: PMID:14528312
supporting_text: >-
Here, we show that Cul3, but not other cullins, binds directly to multiple BTB
domains through a conserved amino-terminal domain.
- reference_id: PMID:14528312
supporting_text: >-
In vitro, Cul3 promoted ubiquitination of Caenorhabditis elegans MEI-1, a
katanin-like protein whose degradation requires the function of both Cul3 and
BTB protein MEL-26.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IDA
original_reference_id: PMID:14528312
review:
summary: >-
The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself
is best represented as the scaffold.
action: MODIFY
reason: >-
For CUL3, ubiquitin ligase complex scaffold activity is the more accurate
molecular function than a catalytic ubiquitin-protein transferase term.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0031208
label: POZ domain binding
evidence_type: IDA
original_reference_id: PMID:14528312
review:
summary: >-
CUL3 binds BTB/POZ-domain substrate adaptors in CRL3 complexes.
action: ACCEPT
reason: >-
POZ/BTB-domain adaptor binding is part of the core CRL3 scaffold architecture.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- term:
id: GO:0000922
label: spindle pole
evidence_type: IDA
original_reference_id: PMID:23213400
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23213400
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:23213400
review:
summary: >-
CUL3 has nuclear localization in some contexts.
action: ACCEPT
reason: >-
Nuclear localization is plausible for CUL3, but the review treats it as a broad
compartment annotation rather than a pathway-specific function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005813
label: centrosome
evidence_type: IDA
original_reference_id: PMID:23213400
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:23213400
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0072686
label: mitotic spindle
evidence_type: IDA
original_reference_id: PMID:23213400
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:1901992
label: positive regulation of mitotic cell cycle phase transition
evidence_type: IMP
original_reference_id: PMID:23213400
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:29276004
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:28395323
review:
summary: >-
CUL3 has cytoplasmic localization in some contexts.
action: ACCEPT
reason: >-
Cytoplasmic localization is compatible with CUL3 CRL scaffold function and should
not be over-interpreted as a specific pathway output.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0036126
label: sperm flagellum
evidence_type: IDA
original_reference_id: PMID:28395323
review:
summary: >-
This localization is not established as a core CUL3 cellular component in this
review.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus
localization; membrane, Golgi, exosome, sperm flagellum, or other specific
locations require source-level confirmation before retention.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0031398
label: positive regulation of protein ubiquitination
evidence_type: IGI
original_reference_id: PMID:24844779
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0031648
label: protein destabilization
evidence_type: IGI
original_reference_id: PMID:24844779
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22748208
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23776465
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:26399832
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8932327
review:
summary: >-
CUL3 can be represented in cytosolic CRL3 pathway contexts.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 scaffold biology, although
repetitive Reactome cytosol rows are left mostly pending for source-level review.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8952631
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8956040
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9712274
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9755505
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9755507
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9758090
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9759169
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9759172
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766645
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766656
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766677
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766687
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005112
label: Notch binding
evidence_type: IPI
original_reference_id: PMID:25401743
review:
summary: >-
This annotation derives from a study of KCTD10 (a CUL3 BTB adaptor) in Notch
signaling during embryonic development, but direct CUL3-Notch binding is not the
core scaffold function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
PMID:25401743 links the CUL3-KCTD10 module to Notch signaling, but substrate
recognition is mediated by the KCTD10 adaptor rather than direct CUL3-Notch binding.
Notch binding is a substrate-contextual, low-information MF that over-attributes
adaptor/substrate recognition to the CUL3 scaffold.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:25401743
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26334369
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27561354
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:27561354
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0071630
label: nuclear protein quality control by the ubiquitin-proteasome system
evidence_type: IDA
original_reference_id: PMID:27561354
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0031145
label: anaphase-promoting complex-dependent catabolic process
evidence_type: IDA
original_reference_id: PMID:10500095
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25270598
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21778237
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5635854
review:
summary: >-
CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
action: ACCEPT
reason: >-
Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway
contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a
cautious broad-compartment cellular component annotation consistent with the other
accepted nucleus/nucleoplasm rows.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5635855
review:
summary: >-
CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
action: ACCEPT
reason: >-
Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway
contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a
cautious broad-compartment cellular component annotation consistent with the other
accepted nucleus/nucleoplasm rows.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5635856
review:
summary: >-
CUL3 is represented as nucleoplasmic in Reactome GLI/Hedgehog CRL3 pathway reactions.
action: ACCEPT
reason: >-
Nuclear/nucleoplasmic localization is plausible for CUL3 in specific pathway
contexts (e.g. SPOP-CUL3 acting on GLI transcription factors); this is treated as a
cautious broad-compartment cellular component annotation consistent with the other
accepted nucleus/nucleoplasm rows.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0007080
label: mitotic metaphase chromosome alignment
evidence_type: IMP
original_reference_id: PMID:17543862
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0007080
label: mitotic metaphase chromosome alignment
evidence_type: IMP
original_reference_id: PMID:19995937
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0045842
label: positive regulation of mitotic metaphase/anaphase transition
evidence_type: IMP
original_reference_id: PMID:17543862
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:24768539
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0016020
label: membrane
evidence_type: HDA
original_reference_id: PMID:19946888
review:
summary: >-
This localization is not established as a core CUL3 cellular component in this
review.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus
localization; membrane, Golgi, exosome, sperm flagellum, or other specific
locations require source-level confirmation before retention.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:19056867
review:
summary: >-
This localization is not established as a core CUL3 cellular component in this
review.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The synthesis supports CRL3 complex membership with cautious cytoplasm/nucleus
localization; membrane, Golgi, exosome, sperm flagellum, or other specific
locations require source-level confirmation before retention.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:19158078
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:22578813
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:23453970
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:23576762
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18397884
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1504190
review:
summary: >-
CUL3 can be represented in cytosolic CRL3 pathway contexts.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 scaffold biology, although
repetitive Reactome cytosol rows are left mostly pending for source-level review.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1504193
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1504213
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5658424
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8952630
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8955241
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8955289
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9018778
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9018787
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9706390
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9929484
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9929486
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9929490
review:
summary: >-
CUL3 is represented as cytosolic in Reactome CRL3 pathway reactions.
action: ACCEPT
reason: >-
Cytosolic localization is compatible with CUL3 CRL3 scaffold function; this is a
broad-compartment cellular component annotation consistent with the other accepted
cytosol/cytoplasm rows for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Cytosol/cytoplasm and nucleus (plausible but evidence here is limited):**
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:23455478
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0000209
label: protein polyubiquitination
evidence_type: IDA
original_reference_id: PMID:19261606
review:
summary: >-
CUL3-containing CRL3 complexes can mediate protein polyubiquitination.
action: ACCEPT
reason: >-
Protein polyubiquitination is a proximal CRL3 output, while substrate-specific
downstream effects should be curated separately.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- term:
id: GO:0004842
label: ubiquitin-protein transferase activity
evidence_type: IDA
original_reference_id: PMID:19261606
qualifier: contributes_to
review:
summary: >-
The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself
is best represented as the scaffold.
action: MODIFY
reason: >-
For CUL3, ubiquitin ligase complex scaffold activity is the more accurate
molecular function than a catalytic ubiquitin-protein transferase term.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19261606
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0031208
label: POZ domain binding
evidence_type: IDA
original_reference_id: PMID:19261606
review:
summary: >-
CUL3 binds BTB/POZ-domain substrate adaptors in CRL3 complexes.
action: ACCEPT
reason: >-
POZ/BTB-domain adaptor binding is part of the core CRL3 scaffold architecture.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:19261606
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0032467
label: positive regulation of cytokinesis
evidence_type: IMP
original_reference_id: PMID:19261606
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:19261606
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0004842
label: ubiquitin-protein transferase activity
evidence_type: IDA
original_reference_id: PMID:15983046
qualifier: contributes_to
review:
summary: >-
The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself
is best represented as the scaffold.
action: MODIFY
reason: >-
For CUL3, ubiquitin ligase complex scaffold activity is the more accurate
molecular function than a catalytic ubiquitin-protein transferase term.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:15983046
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0006513
label: protein monoubiquitination
evidence_type: IDA
original_reference_id: PMID:22358839
review:
summary: >-
Some CUL3-adaptor complexes mediate monoubiquitination rather than degradative
polyubiquitination.
action: KEEP_AS_NON_CORE
reason: >-
Protein monoubiquitination is a valid adaptor/substrate-specific CUL3 output, but
it is not the main degradative CRL3 process summarized as core.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
evidence_type: IDA
original_reference_id: PMID:22358839
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0007229
label: integrin-mediated signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0017145
label: stem cell division
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:22358839
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0040016
label: embryonic cleavage
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: >-
This automated or broad pathway annotation is downstream of CUL3-adaptor substrate
biology rather than a core CUL3 function.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The Falcon synthesis warns against promoting broad pathway, development, disease,
or phenotype terms to core CUL3 annotations without direct mechanistic evidence at
the annotated pathway node.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0048208
label: COPII vesicle coating
evidence_type: IMP
original_reference_id: PMID:22358839
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18826954
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0004842
label: ubiquitin-protein transferase activity
evidence_type: IDA
original_reference_id: PMID:19782033
qualifier: contributes_to
review:
summary: >-
The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself
is best represented as the scaffold.
action: MODIFY
reason: >-
For CUL3, ubiquitin ligase complex scaffold activity is the more accurate
molecular function than a catalytic ubiquitin-protein transferase term.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0016477
label: cell migration
evidence_type: IMP
original_reference_id: PMID:19782033
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:19782033
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:19782033
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0035024
label: negative regulation of Rho protein signal transduction
evidence_type: IMP
original_reference_id: PMID:19782033
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043149
label: stress fiber assembly
evidence_type: IMP
original_reference_id: PMID:19782033
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:19782033
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
evidence_type: IDA
original_reference_id: PMID:20389280
review:
summary: >-
CUL3-containing CRL3 complexes support ubiquitin-dependent proteasomal substrate
degradation.
action: ACCEPT
reason: >-
Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output
for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination
remains a caveat for some substrates.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews
explicitly describe substrate ubiquitination “for proteasomal degradation” as a
CRL3 output
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
not all CUL3-dependent ubiquitination is degradative
- term:
id: GO:0004842
label: ubiquitin-protein transferase activity
evidence_type: IDA
original_reference_id: PMID:20389280
qualifier: contributes_to
review:
summary: >-
The ubiquitin ligase activity belongs to the assembled CRL3 complex; CUL3 itself
is best represented as the scaffold.
action: MODIFY
reason: >-
For CUL3, ubiquitin ligase complex scaffold activity is the more accurate
molecular function than a catalytic ubiquitin-protein transferase term.
proposed_replacement_terms:
- id: GO:0160072
label: ubiquitin ligase complex scaffold activity
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
evidence best supports a CUL3 annotation consistent with **“ubiquitin ligase
complex scaffold activity”** / **E3 ligase scaffold** rather than
“ubiquitin-protein transferase activity” (which is catalytic and typically
attributed to the E2/E3 catalytic machinery rather than the scaffold)
- term:
id: GO:0005827
label: polar microtubule
evidence_type: IDA
original_reference_id: PMID:19995937
review:
summary: >-
This cytoskeleton/centrosome/spindle localization is likely context-specific for
CUL3-adaptor biology.
action: KEEP_AS_NON_CORE
reason: >-
Centrosome, spindle, and cytoskeletal annotations may be valid in specific mitotic
or adaptor contexts but are not the core CUL3 location.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
**Membrane/centrosome/cytoskeleton claims require caution:**
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:17543862
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:19995937
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:20389280
review:
summary: >-
CUL3-containing CRL3 complexes mediate protein ubiquitination.
action: ACCEPT
reason: >-
Protein ubiquitination is the proximal biological process output of CUL3 scaffold
function in CRL3 E3 ligase complexes.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example,
CRL3^KLHL22 assays support ubiquitination activity dependence on CUL3 structural
motifs
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:17543862
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:19995937
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0031463
label: Cul3-RING ubiquitin ligase complex
evidence_type: IDA
original_reference_id: PMID:20389280
review:
summary: >-
CUL3 is a core component of Cul3-RING ubiquitin ligase complexes.
action: ACCEPT
reason: >-
CRL3 complex membership is a core cellular component annotation for CUL3.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a
**RING protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain
substrate adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
direct structural evidence places CUL3 in CRL3 assemblies containing RBX1 and
BTB adaptors
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18573101
review:
summary: >-
This is a generic protein binding annotation supported by a pairwise or
high-throughput interaction; the informative CUL3 interactions (BTB/POZ adaptor
binding, RBX1, regulators) are captured by more specific terms.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Bare protein binding (GO:0005515) is low-information and should not be retained as a
core CUL3 molecular function. CUL3's biologically meaningful interactions with
BTB/POZ-domain substrate adaptors are already captured by POZ domain binding
(GO:0031208), and its scaffold role by ubiquitin ligase complex scaffold activity
(GO:0160072). Many of these rows derive from large-scale interactome or affinity
screens and capture adaptor, substrate, or non-specific partners rather than a
distinct CUL3 function.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Avoid annotating CUL3 with generic “protein binding” or “ubiquitin protein
ligase binding” unless the evidence is specifically required for MF, because
these terms are often **low-information** and may reflect experimental detection
rather than biological specificity.
- term:
id: GO:0000082
label: G1/S transition of mitotic cell cycle
evidence_type: TAS
original_reference_id: PMID:8681378
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: TAS
original_reference_id: PMID:9733711
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
- term:
id: GO:0097193
label: intrinsic apoptotic signaling pathway
evidence_type: TAS
original_reference_id: PMID:8681378
review:
summary: >-
This is a substrate-, adaptor-, or phenotype-specific downstream process for CUL3.
action: KEEP_AS_NON_CORE
reason: >-
The process can be retained as non-core where source evidence supports a specific
CUL3-adaptor substrate context, but the core CUL3 function remains CRL3
scaffold-mediated ubiquitination.
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
oxidative stress response, blood pressure/electrolyte phenotypes,
neurodevelopmental phenotypes, or cancer-associated phenotypes can be downstream
of CUL3-dependent substrate regulation. These should not be treated as core CUL3
BP terms without direct mechanistic evidence that CUL3’s scaffold activity is
required in the specific pathway node being annotated.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to
orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000108
title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
links
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10500095
title: Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian
cells.
findings: []
- id: PMID:12609982
title: TIP120A associates with cullins and modulates ubiquitin ligase activity.
findings: []
- id: PMID:14528312
title: Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.
findings: []
- id: PMID:15107402
title: RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex.
findings: []
- id: PMID:15601839
title: BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination
by the Cullin 3-Roc1 ligase.
findings: []
- id: PMID:15983046
title: Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3,
targets Keap1 for degradation by a proteasome-independent pathway.
findings: []
- id: PMID:17543862
title: A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating
mitotic progression and completion of cytokinesis in human cells.
findings: []
- id: PMID:18397884
title: Regulation of TIP60 by ATF2 modulates ATM activation.
findings: []
- id: PMID:18573101
title: KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases.
findings: []
- id: PMID:18775313
title: UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover.
findings: []
- id: PMID:18826954
title: SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation.
findings: []
- id: PMID:18850735
title: Characterization of the human COP9 signalosome complex using affinity purification
and mass spectrometry.
findings: []
- id: PMID:19056867
title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
findings: []
- id: PMID:19158078
title: Control of rapsyn stability by the CUL-3-containing E3 ligase complex.
findings: []
- id: PMID:19261606
title: The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal
mitosis in mammalian cells.
findings: []
- id: PMID:19427028
title: Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8
mediate extrinsic apoptosis signaling.
findings: []
- id: PMID:19615732
title: Defining the human deubiquitinating enzyme interaction landscape.
findings: []
- id: PMID:19617556
title: The human Dcn1-like protein DCNL3 promotes Cul3 neddylation at membranes.
findings: []
- id: PMID:19782033
title: Cullin mediates degradation of RhoA through evolutionarily conserved BTB
adaptors to control actin cytoskeleton structure and cell movement.
findings: []
- id: PMID:19946888
title: Defining the membrane proteome of NK cells.
findings: []
- id: PMID:19995937
title: The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules
in anaphase and is required for cytokinesis.
findings: []
- id: PMID:20389280
title: The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control
interferon responses.
findings: []
- id: PMID:20554658
title: Kelch-like homologue 9 mutation is associated with an early onset autosomal
dominant distal myopathy.
findings: []
- id: PMID:20562859
title: Network organization of the human autophagy system.
findings: []
- id: PMID:21145461
title: Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative
proteomics.
findings: []
- id: PMID:21577200
title: Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis
of the oncogenic co-activator SRC-3/AIB1.
findings: []
- id: PMID:21778237
title: COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin
RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein
1) binding.
findings: []
- id: PMID:21828050
title: Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal
dominant retinitis pigmentosa causative mutation.
findings: []
- id: PMID:21988832
title: Toward an understanding of the protein interaction network of the human liver.
findings: []
- id: PMID:22358839
title: Ubiquitin-dependent regulation of COPII coat size and function.
findings: []
- id: PMID:22466964
title: NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
findings: []
- id: PMID:22542517
title: KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase.
findings: []
- id: PMID:22578813
title: Translational homeostasis via the mRNA cap-binding protein, eIF4E.
findings: []
- id: PMID:22632832
title: Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin
ligase.
findings: []
- id: PMID:22748208
title: A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the
ubiquitin-proteasome system.
findings: []
- id: PMID:22939624
title: Quantitative analysis of HSP90-client interactions reveals principles of
substrate recognition.
findings: []
- id: PMID:23213400
title: The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A.
findings: []
- id: PMID:23453970
title: Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension.
findings: []
- id: PMID:23455478
title: Ubiquitylation-dependent localization of PLK1 in mitosis.
findings: []
- id: PMID:23563313
title: CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling.
findings: []
- id: PMID:23576762
title: Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination
and degradation of WNK4.
findings: []
- id: PMID:23665031
title: Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation.
findings: []
- id: PMID:23776465
title: Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear localization through
Nedd8 modification.
findings: []
- id: PMID:24145166
title: Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation and promotes
cell cycle progression.
findings: []
- id: PMID:24192928
title: Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity
and nuclear localization.
findings: []
- id: PMID:24768539
title: K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase
Regulates Protein Trafficking.
findings: []
- id: PMID:24844779
title: Hypoxia-responsive microRNA-101 promotes angiogenesis via heme oxygenase-1/vascular
endothelial growth factor axis by targeting cullin 3.
findings: []
- id: PMID:25270598
title: Ubiquitin-proteasome system controls ciliogenesis at the initial step of
axoneme extension.
findings: []
- id: PMID:25401743
title: KCTD10 is involved in the cardiovascular system and Notch signaling during
early embryonic development.
findings: []
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings: []
- id: PMID:25502805
title: A massively parallel pipeline to clone DNA variants and examine molecular
phenotypes of human disease mutations.
findings: []
- id: PMID:25619834
title: KLHL39 suppresses colon cancer metastasis by blocking KLHL20-mediated PML
and DAPK ubiquitination.
findings: []
- id: PMID:25684205
title: CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially
restrict TIAM1-RAC1 signaling.
findings: []
- id: PMID:26334369
title: Structural Insights into KCTD Protein Assembly and Cullin3 Recognition.
findings: []
- id: PMID:26399832
title: Cell-fate determination by ubiquitin-dependent regulation of translation.
findings: []
- id: PMID:26906416
title: Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.
findings: []
- id: PMID:26949739
title: Identification of Human Neuronal Protein Complexes Reveals Biochemical Activities
and Convergent Mechanisms of Action in Autism Spectrum Disorders.
findings: []
- id: PMID:27152988
title: The BTB domains of the potassium channel tetramerization domain proteins
prevalently assume pentameric states.
findings: []
- id: PMID:27561354
title: Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune
DNA-end resection.
findings: []
- id: PMID:27708159
title: Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2
deficiency in mice.
findings: []
- id: PMID:28169274
title: Armc5 deletion causes developmental defects and compromises T-cell immune
responses.
findings: []
- id: PMID:28395323
title: 'Defining the human sperm microtubulome: an integrated genomics approach.'
findings: []
- id: PMID:29249570
title: Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.
findings: []
- id: PMID:29276004
title: Missense Variants in RHOBTB2 Cause a Developmental and Epileptic Encephalopathy
in Humans, and Altered Levels Cause Neurological Defects in Drosophila.
findings: []
- id: PMID:29769719
title: KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis
and ageing.
findings: []
- id: PMID:30190310
title: Dimerization quality control ensures neuronal development and survival.
findings: []
- id: PMID:31515488
title: Extensive disruption of protein interactions by genetic variants across the
allele frequency spectrum in human populations.
findings: []
- id: PMID:31652307
title: Kelch-like protein 5-mediated ubiquitination of lysine 183 promotes proteasomal
degradation of sphingosine kinase 1.
findings: []
- id: PMID:31898230
title: 'CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases.'
findings: []
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings: []
- id: PMID:32814053
title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
and Uncovers Widespread Protein Aggregation in Affected Brains.
findings: []
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the human
interactome.
findings: []
- id: PMID:34591642
title: A protein network map of head and neck cancer reveals PIK3CA mutant drug
sensitivity.
findings: []
- id: PMID:35512704
title: Systematic discovery of mutation-directed neo-protein-protein interactions
in cancer.
findings: []
- id: PMID:35687106
title: ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal
hyperplasia.
findings: []
- id: PMID:35862218
title: ARMC5-CUL3 E3 ligase targets full-length SREBF in adrenocortical tumors.
findings: []
- id: PMID:36394357
title: XAF1 prevents hyperproduction of type I interferon upon viral infection by
targeting IRF7.
findings: []
- id: PMID:37207277
title: Using brain cell-type-specific protein interactomes to interpret neurodevelopmental
genetic signals in schizophrenia.
findings: []
- id: PMID:37628845
title: The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.
findings: []
- id: PMID:37788672
title: Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic
enzyme.
findings: []
- id: PMID:38225382
title: Systematic discovery of protein interaction interfaces using AlphaFold and
experimental validation.
findings: []
- id: PMID:38225631
title: ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation
increases neural tube defect risks in mice and humans.
findings: []
- id: PMID:39504960
title: Redundant pathways for removal of defective RNA polymerase II complexes at
a promoter-proximal pause checkpoint.
findings: []
- id: PMID:39667934
title: CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form parallel mechanisms
to control early stages of RNA Pol II transcription.
findings: []
- id: PMID:40205054
title: Multimodal cell maps as a foundation for structural and functional genomics.
findings: []
- id: PMID:8681378
title: cul-1 is required for cell cycle exit in C. elegans and identifies a novel
gene family.
findings: []
- id: PMID:9733711
title: Cloning and expression analysis of a novel salicylate suppressible gene,
Hs-CUL-3, a member of cullin/Cdc53 family.
findings: []
- id: Reactome:R-HSA-1504190
title: DVL is ubiquitinated by CUL3:KLHL12:RBX1
findings: []
- id: Reactome:R-HSA-1504193
title: Ubiquitinated DVL is degraded by the proteasome
findings: []
- id: Reactome:R-HSA-1504213
title: DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex
findings: []
- id: Reactome:R-HSA-5635854
title: GLI2,3 are degraded by the proteasome
findings: []
- id: Reactome:R-HSA-5635855
title: phosphorylated GLI proteins bind SPOP:CUL3:RBX1
findings: []
- id: Reactome:R-HSA-5635856
title: SPOP:CUL3:RBX1 ubiquitinates GLI2,3
findings: []
- id: Reactome:R-HSA-5658424
title: KBTBD7:CUL3:RBX1 ubiquitinates NF1
findings: []
- id: Reactome:R-HSA-8932327
title: NFE2L2 binds KEAP1:NEDD8-CUL3:RBX1
findings: []
- id: Reactome:R-HSA-8952630
title: NEDD8:AcM-UBE2M binds CRL3 E3 ubiquitin ligase complex
findings: []
- id: Reactome:R-HSA-8952631
title: AcM-UBE2M transfers NEDD8 to CRL3 E3 ubiquitin ligase complex
findings: []
- id: Reactome:R-HSA-8955241
title: CAND1 binds cytosolic CRL E3 ubiquitin ligases
findings: []
- id: Reactome:R-HSA-8955289
title: COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
findings: []
- id: Reactome:R-HSA-8956040
title: COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
findings: []
- id: Reactome:R-HSA-9018778
title: RHOBTB1 binds interacting proteins at the endosome membrane
findings: []
- id: Reactome:R-HSA-9018787
title: RHOBTB2 binds interacting proteins at the endosome membrane
findings: []
- id: Reactome:R-HSA-9706390
title: RHOBTB3 binds interacting proteins at trans-Golgi network
findings: []
- id: Reactome:R-HSA-9712274
title: NFE2L2 inducers bind to KEAP1:CUL3:RBX1:NFE2L2
findings: []
- id: Reactome:R-HSA-9755505
title: KEAP1:NEDD8-CUL3:RBX1 complex ubiquitinates NFE2L2
findings: []
- id: Reactome:R-HSA-9755507
title: UBXN7:UBF1:NPLOC4:VCP hexamer binds NFE2L2:CRL3 complex
findings: []
- id: Reactome:R-HSA-9758090
title: Ubiquitinated NFE2L2 is extracted from CRL3 complex for degradation
findings: []
- id: Reactome:R-HSA-9759169
title: p-S349 SQSTM1 oligomer binds KEAP1:CUL3:RBX1
findings: []
- id: Reactome:R-HSA-9759172
title: KEAP1:CUL3:RBX1 ubiquitinates p-S349 SQSTM1 oligomer
findings: []
- id: Reactome:R-HSA-9766645
title: CUL3:RBX1 ubiquitinates KEAP1
findings: []
- id: Reactome:R-HSA-9766656
title: RBX1:CUL3 dissociates from forming autophagosome
findings: []
- id: Reactome:R-HSA-9766677
title: MAP1LC3B binds KEAP1 and SQSTM1
findings: []
- id: Reactome:R-HSA-9766687
title: SESN1,SESN1 bind SQSTM1 and KEAP1
findings: []
- id: Reactome:R-HSA-9929484
title: SPOP:CUL3:RBX1 binds to CD274
findings: []
- id: Reactome:R-HSA-9929486
title: SPOP-mediated degradation of CD274 by 26S Proteosome
findings: []
- id: Reactome:R-HSA-9929490
title: CD274 ubiquitination by SPOP:CUL3:RBX1 complex
findings: []
- id: file:human/CUL3/CUL3-deep-research-falcon.md
title: Falcon deep research report on CUL3
findings: []
core_functions:
- molecular_function:
id: GO:0160072
label: ubiquitin ligase complex scaffold activity
description: >-
CUL3 is the scaffold of CRL3 cullin-RING E3 ubiquitin ligase complexes,
connecting RBX1/E2 catalytic machinery to BTB-domain substrate adaptors.
This scaffold function drives substrate ubiquitination, including
polyubiquitination and proteasome-mediated degradation in many adaptor
contexts, while non-degradative ubiquitination and downstream phenotypes are
substrate-specific.
directly_involved_in:
- id: GO:0016567
label: protein ubiquitination
- id: GO:0000209
label: protein polyubiquitination
- id: GO:0043161
label: proteasome-mediated ubiquitin-dependent protein catabolic process
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005634
label: nucleus
supported_by:
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
CUL3 is the **central scaffold** of CRL3 ubiquitin ligases, bridging (i) a **RING
protein (RBX1)** that recruits E2~ubiquitin and (ii) **BTB-domain substrate
adaptor/receptor proteins** that recruit specific substrates.
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Multiple CRL3 systems demonstrate ubiquitination output; for example, CRL3^KLHL22
assays support ubiquitination activity dependence on CUL3 structural motifs
- reference_id: file:human/CUL3/CUL3-deep-research-falcon.md
supporting_text: >-
Proteasomal targeting is a canonical outcome for many CRLs, and reviews explicitly
describe substrate ubiquitination “for proteasomal degradation” as a CRL3 output
proposed_new_terms: []
suggested_questions:
- question: >-
Which generic protein-binding rows correspond to direct CUL3-BTB adaptor,
RBX1, substrate, or regulator interactions that should be converted to more
informative terms?
- question: >-
Which substrate-specific pathway and phenotype annotations have direct CUL3
scaffold-dependent evidence rather than adaptor/substrate or disease-context
inference?
- question: >-
Which annotations should distinguish CUL3's core scaffold activity from CRL3
regulation by neddylation, deneddylation, CSN, and CAND1-mediated adaptor exchange?
suggested_experiments:
- description: >-
Review CRL3 adaptor modules one at a time, separating CUL3 scaffold activity
from adaptor-specific substrate recognition and downstream pathway outputs.
- description: >-
Prioritize source-level review of membrane, Golgi, centrosome, spindle,
cytoskeleton, and synaptic localization claims before retaining them as CUL3
cellular component annotations.