Cbl is a RING-type E3 ubiquitin-protein ligase and phosphotyrosine-binding adaptor that recognizes activated receptor tyrosine kinases and other signaling proteins. It ubiquitinates receptors and signaling components to promote endocytosis, lysosomal or proteasomal turnover, and negative feedback on EGFR, PDGFRA, KIT, CSF1R, SRC-family, and immune-receptor signaling pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0061630
ubiquitin protein ligase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005886
plasma membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: plasma membrane is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0007165
signal transduction
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: signal transduction is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0045121
membrane raft
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: membrane raft is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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|
GO:0030971
receptor tyrosine kinase binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: receptor tyrosine kinase binding is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0001784
phosphotyrosine residue binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: phosphotyrosine residue binding is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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|
GO:0004842
ubiquitin-protein transferase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: ubiquitin-protein transferase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005509
calcium ion binding
|
IEA
GO_REF:0000002 |
MARK AS OVER ANNOTATED |
Summary: calcium ion binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: cytoplasm is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005794
Golgi apparatus
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Golgi apparatus is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: plasma membrane is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005929
cilium
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
Reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
Supporting Evidence:
PMID:29237719
c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0007166
cell surface receptor signaling pathway
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: cell surface receptor signaling pathway is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0008270
zinc ion binding
|
IEA
GO_REF:0000043 |
MARK AS OVER ANNOTATED |
Summary: zinc ion binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0016740
transferase activity
|
IEA
GO_REF:0000043 |
MODIFY |
Summary: The annotation captures a real aspect of Cbl biology, but transferase activity is less precise than GO:0061630 ubiquitin protein ligase activity for this gene.
Reason: Use a more specific GO term supported by the gene product role
Proposed replacements:
ubiquitin protein ligase activity
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0023051
regulation of signaling
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: The annotation captures a real aspect of Cbl biology, but regulation of signaling is less precise than GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway for this gene.
Reason: Use a more specific GO term supported by the gene product role
Proposed replacements:
negative regulation of epidermal growth factor receptor signaling pathway
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0046872
metal ion binding
|
IEA
GO_REF:0000120 |
MARK AS OVER ANNOTATED |
Summary: metal ion binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0061630
ubiquitin protein ligase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:1902531
regulation of intracellular signal transduction
|
IEA
GO_REF:0000117 |
MODIFY |
Summary: The annotation captures a real aspect of Cbl biology, but regulation of intracellular signal transduction is less precise than GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway for this gene.
Reason: Use a more specific GO term supported by the gene product role
Proposed replacements:
negative regulation of epidermal growth factor receptor signaling pathway
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:2000583
regulation of platelet-derived growth factor receptor-alpha signaling pathway
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: regulation of platelet-derived growth factor receptor-alpha signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:12559036 CD2AP/CMS regulates endosome morphology and traffic to the d... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:12559036
CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0005515
protein binding
|
IPI
PMID:23374343 Induction of Siglec-G by RNA viruses inhibits the innate imm... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:23374343
Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005515
protein binding
|
IPI
PMID:23799367 Threshold-controlled ubiquitination of the EGFR directs rece... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:23799367
Threshold-controlled ubiquitination of the EGFR directs receptor fate.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:24440350 Targeting of the MET receptor tyrosine kinase by small molec... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:24440350
2014 Jan 17. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0005515
protein binding
|
IPI
PMID:27474268 Co-recruitment analysis of the CBL and CBLB signalosomes in ... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:27474268
Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0005515
protein binding
|
IPI
PMID:7657591 Tyrosine phosphorylation of the c-cbl proto-oncogene protein... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:7657591
Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:9890970 Fyn associates with Cbl and phosphorylates tyrosine 731 in C... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:9890970
Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for phosphatidylinositol 3-kinase.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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|
GO:0000209
protein polyubiquitination
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: protein polyubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005829
cytosol
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005925
focal adhesion
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: focal adhesion is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: ubiquitin-dependent protein catabolic process is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006513
protein monoubiquitination
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: protein monoubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006974
DNA damage response
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: DNA damage response is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0008584
male gonad development
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: male gonad development is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0010332
response to gamma radiation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to gamma radiation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0014823
response to activity
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to activity is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0016567
protein ubiquitination
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: protein ubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0017124
SH3 domain binding
|
IEA
GO_REF:0000120 |
MARK AS OVER ANNOTATED |
Summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0019901
protein kinase binding
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: protein kinase binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0030424
axon
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: axon is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0030426
growth cone
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: growth cone is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0033574
response to testosterone
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to testosterone is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0036120
cellular response to platelet-derived growth factor stimulus
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to platelet-derived growth factor stimulus is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0036312
phosphatidylinositol 3-kinase regulatory subunit binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: phosphatidylinositol 3-kinase regulatory subunit binding is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042594
response to starvation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to starvation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0043066
negative regulation of apoptotic process
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: negative regulation of apoptotic process is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0043303
mast cell degranulation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: mast cell degranulation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0045471
response to ethanol
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: response to ethanol is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0046875
ephrin receptor binding
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0048260
positive regulation of receptor-mediated endocytosis
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: positive regulation of receptor-mediated endocytosis is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0048471
perinuclear region of cytoplasm
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: perinuclear region of cytoplasm is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050821
protein stabilization
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: protein stabilization is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050860
negative regulation of T cell receptor signaling pathway
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of T cell receptor signaling pathway is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050868
negative regulation of T cell activation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: negative regulation of T cell activation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0051865
protein autoubiquitination
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: protein autoubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0070534
protein K63-linked ubiquitination
|
IEA
GO_REF:0000107 |
MODIFY |
Summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling receptors, but the available evidence does not establish K63 linkage specificity.
Reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
Proposed replacements:
protein ubiquitination
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0071456
cellular response to hypoxia
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to hypoxia is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:1990090
cellular response to nerve growth factor stimulus
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: cellular response to nerve growth factor stimulus is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:1990782
protein tyrosine kinase binding
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: protein tyrosine kinase binding is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005794
Golgi apparatus
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: Golgi apparatus is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005886
plasma membrane
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: plasma membrane is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005929
cilium
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
Reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
Supporting Evidence:
PMID:29237719
c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: ubiquitin-dependent protein catabolic process is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0016567
protein ubiquitination
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: protein ubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0017124
SH3 domain binding
|
ISO
GO_REF:0000119 |
MARK AS OVER ANNOTATED |
Summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0043066
negative regulation of apoptotic process
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: negative regulation of apoptotic process is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0046875
ephrin receptor binding
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0048260
positive regulation of receptor-mediated endocytosis
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: positive regulation of receptor-mediated endocytosis is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050821
protein stabilization
|
ISO
GO_REF:0000119 |
MARK AS OVER ANNOTATED |
Summary: protein stabilization is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050860
negative regulation of T cell receptor signaling pathway
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: negative regulation of T cell receptor signaling pathway is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050868
negative regulation of T cell activation
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: negative regulation of T cell activation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0070534
protein K63-linked ubiquitination
|
ISO
GO_REF:0000119 |
MODIFY |
Summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling receptors, but the available evidence does not establish K63 linkage specificity.
Reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
Proposed replacements:
protein ubiquitination
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0097229
sperm end piece
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: sperm end piece is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0000209
protein polyubiquitination
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: protein polyubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005925
focal adhesion
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: focal adhesion is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006513
protein monoubiquitination
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: protein monoubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0017124
SH3 domain binding
|
ISO
GO_REF:0000096 |
MARK AS OVER ANNOTATED |
Summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0019901
protein kinase binding
|
ISO
GO_REF:0000096 |
MARK AS OVER ANNOTATED |
Summary: protein kinase binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0030424
axon
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: axon is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0030426
growth cone
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: growth cone is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0036312
phosphatidylinositol 3-kinase regulatory subunit binding
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: phosphatidylinositol 3-kinase regulatory subunit binding is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0043066
negative regulation of apoptotic process
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: negative regulation of apoptotic process is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0048471
perinuclear region of cytoplasm
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: perinuclear region of cytoplasm is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0051865
protein autoubiquitination
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: protein autoubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:1990782
protein tyrosine kinase binding
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: protein tyrosine kinase binding is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
TAS
Reactome:R-MMU-9763892 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050821
protein stabilization
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: protein stabilization is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050860
negative regulation of T cell receptor signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of T cell receptor signaling pathway is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0050868
negative regulation of T cell activation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: negative regulation of T cell activation is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0070534
protein K63-linked ubiquitination
|
ISS
GO_REF:0000024 |
MODIFY |
Summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling receptors, but the available evidence does not establish K63 linkage specificity.
Reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
Proposed replacements:
protein ubiquitination
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IMP
PMID:12754251 Cbl-mediated ubiquitinylation is required for lysosomal sort... |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:12754251
2003 May 18. Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth factor receptor but is dispensable for endocytosis.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IMP
PMID:15962011 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epiderma... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:15962011
Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i... |
ACCEPT |
Summary: plasma membrane is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:15383614
Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0016567
protein ubiquitination
|
ISO
PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy... |
ACCEPT |
Summary: protein ubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:11823423
A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IGI
PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy... |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:11823423
A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IGI
PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:11823423
A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IMP
PMID:12754251 Cbl-mediated ubiquitinylation is required for lysosomal sort... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:12754251
2003 May 18. Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth factor receptor but is dispensable for endocytosis.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0070086
ubiquitin-dependent endocytosis
|
ISO
PMID:11823423 A mutant EGF-receptor defective in ubiquitylation and endocy... |
ACCEPT |
Summary: ubiquitin-dependent endocytosis is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:11823423
A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0006511
ubiquitin-dependent protein catabolic process
|
IMP
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: ubiquitin-dependent protein catabolic process is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0016567
protein ubiquitination
|
IDA
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: protein ubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IDA
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
IMP
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IDA
PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:15383614
Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IDA
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0061630
ubiquitin protein ligase activity
|
IMP
PMID:23457600 Berberine inhibits proliferation and down-regulates epiderma... |
ACCEPT |
Summary: ubiquitin protein ligase activity is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:23457600
Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0070086
ubiquitin-dependent endocytosis
|
IMP
PMID:15383614 c-Cbl directs EGF receptors into an endocytic pathway that i... |
ACCEPT |
Summary: ubiquitin-dependent endocytosis is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:15383614
Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0016600
flotillin complex
|
IDA
PMID:11001060 CAP defines a second signalling pathway required for insulin... |
KEEP AS NON CORE |
Summary: flotillin complex is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
PMID:11001060
CAP defines a second signalling pathway required for insulin-stimulated glucose transport.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005515
protein binding
|
IPI
PMID:9447983 A novel, multifuntional c-Cbl binding protein in insulin rec... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:9447983
A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9680646 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9680706 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9682158 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9682182 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9763891 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9763892 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005829
cytosol
|
TAS
Reactome:R-MMU-9817994 |
ACCEPT |
Summary: cytosol is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0016567
protein ubiquitination
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: protein ubiquitination is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0032487
regulation of Rap protein signal transduction
|
IMP
PMID:12671687 Negative regulation of Rap1 activation by the Cbl E3 ubiquit... |
KEEP AS NON CORE |
Summary: regulation of Rap protein signal transduction is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
PMID:12671687
Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005794
Golgi apparatus
|
IDA
PMID:29237719 IFT20 modulates ciliary PDGFRα signaling by regulating the s... |
REMOVE |
Summary: The cited study supports IFT20/Golgi effects on ciliary PDGFR signaling and Cbl stability, but does not directly establish Cbl as a Golgi-localized gene product.
Reason: Cited evidence does not support this gene-product annotation
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GO:0005929
cilium
|
IDA
PMID:29237719 IFT20 modulates ciliary PDGFRα signaling by regulating the s... |
KEEP AS NON CORE |
Summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
Reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
Supporting Evidence:
PMID:29237719
c-Cbl becomes enriched in the cilium, and the receptor is subsequently ubiquitinated and internalized
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:2000583
regulation of platelet-derived growth factor receptor-alpha signaling pathway
|
IMP
PMID:29237719 IFT20 modulates ciliary PDGFRα signaling by regulating the s... |
ACCEPT |
Summary: regulation of platelet-derived growth factor receptor-alpha signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
PMID:29237719
Dec 13. IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:8551236 Association of tyrosine protein kinase Zap-70 with the proto... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:8551236
Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:21830225 SH3KBP1-binding protein 1 prevents epidermal growth factor r... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:21830225
Aug 9. SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0006511
ubiquitin-dependent protein catabolic process
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: ubiquitin-dependent protein catabolic process is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0042059
negative regulation of epidermal growth factor receptor signaling pathway
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: negative regulation of epidermal growth factor receptor signaling pathway is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0048260
positive regulation of receptor-mediated endocytosis
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: positive regulation of receptor-mediated endocytosis is directly supported as part of the core molecular function, direct pathway role, or primary localization of Cbl.
Reason: Directly supported core function, process, or location
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0005515
protein binding
|
IPI
PMID:11152963 SETA is a multifunctional adapter protein with three SH3 dom... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:11152963
SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0005515
protein binding
|
IPI
PMID:16455755 Spatial and temporal regulation of GLUT4 translocation by fl... |
MARK AS OVER ANNOTATED |
Summary: protein binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:16455755
Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0046875
ephrin receptor binding
|
IPI
PMID:18034775 Ligand binding induces Cbl-dependent EphB1 receptor degradat... |
KEEP AS NON CORE |
Summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
PMID:18034775
2007 Dec 19. Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
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GO:0006468
protein phosphorylation
|
ISS
GO_REF:0000024 |
REMOVE |
Summary: CBL is phosphorylated by tyrosine kinases but is not itself a protein kinase; the direct catalytic role is ubiquitin transfer.
Reason: Annotation conflicts with known molecular function or domain architecture
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0045453
bone resorption
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: bone resorption is biologically plausible for Cbl but represents a context-specific pathway, localization, interaction, phenotype, or downstream response rather than the primary core function.
Reason: Supported secondary or context-specific role
Supporting Evidence:
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
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GO:0017124
SH3 domain binding
|
IPI
PMID:9447983 A novel, multifuntional c-Cbl binding protein in insulin rec... |
MARK AS OVER ANNOTATED |
Summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports a more specific signaling, catalytic, adaptor, or localization role.
Reason: Overly broad or uninformative relative to the supported core function
Supporting Evidence:
PMID:9447983
A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes.
UniProt:P22682
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.
file:mouse/Cbl/Cbl-deep-research-falcon.md
Falcon deep research report reviewed for GO term specificity, core-function context, and evidence synthesis.
|
provider: falcon
model: Edison Scientific Literature
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start_time: '2026-05-03T13:47:30.165385'
end_time: '2026-05-03T14:04:56.189304'
duration_seconds: 1046.02
template_file: templates/gene_research_go_focused.md
template_variables:
organism: mouse
gene_id: Cbl
gene_symbol: Cbl
uniprot_accession: P22682
protein_description: 'RecName: Full=E3 ubiquitin-protein ligase CBL; EC=2.3.2.27
{ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:20100865}; AltName: Full=Casitas
B-lineage lymphoma proto-oncogene; AltName: Full=Proto-oncogene c-Cbl; AltName:
Full=RING-type E3 ubiquitin transferase CBL {ECO:0000305}; AltName: Full=Signal
transduction protein CBL;'
gene_info: Name=Cbl;
organism_full: Mus musculus (Mouse).
protein_family: Not specified in UniProt
protein_domains: Adaptor_Cbl. (IPR024162); Adaptor_Cbl_EF_hand-like. (IPR014741);
Adaptor_Cbl_N_dom_sf. (IPR036537); Adaptor_Cbl_N_hlx. (IPR003153); Adaptor_Cbl_SH2-like.
(IPR014742)
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citation_count: 29
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Cbl' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Cbl (gene ID: Cbl, UniProt: P22682) in mouse.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
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.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Cbl' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Cbl (gene ID: Cbl, UniProt: P22682) in mouse.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The target protein is mouse c-Cbl (gene: Cbl; UniProt: P22682), a member of the CBL-family RING-type E3 ubiquitin ligases. Recent reviews and primary studies consistently describe CBL proteins (c-Cbl, Cbl-b, Cbl-c) as E3 ligases with a conserved N-terminal tyrosine kinase binding domain (TKB/TKBD) and a catalytic RING finger separated by a linker helix region (LHR), matching the UniProt domain expectations for mouse Cbl (Adaptor_Cbl/TKB-related modules). (zutshi2024cblandcblb pages 1-2, nath2024mechanismsofcblmediated pages 1-3, ren2024theroleof pages 1-2)
Ubiquitination is a post-translational modification in which ubiquitin is covalently attached to substrate proteins through an enzymatic cascade (E1 activating enzyme → E2 conjugating enzyme → E3 ligase). Cbl-family proteins are RING-type E3 ligases, meaning they do not form a catalytic ubiquitin thioester intermediate; instead, they bring an E2~ubiquitin conjugate into proximity with the substrate to enable transfer. (nath2024mechanismsofcblmediated pages 1-3)
Across receptor systems, c-Cbl is best understood as an activation-dependent negative regulator of signaling that couples recognition of phosphotyrosine-containing activated signaling complexes to ubiquitin-dependent downregulation (often routing to lysosomes for receptor degradation) and/or proteasomal degradation of signaling proteins. (ren2024theroleof pages 1-2, duan2003cblmediatedubiquitinylationis pages 1-1, nath2024mechanismsofcblmediated pages 1-3)
CBL proteins share a modular architecture:
- TKBD/TKB: a composite domain comprising a 4-helix bundle, EF-hand, and an SH2-like phosphotyrosine-recognition module that mediates binding to phosphorylated targets. (nath2024mechanismsofcblmediated pages 1-3)
- Linker helix region (LHR): a regulatory segment connecting TKBD to the RING; phosphorylation within this region is central to activation. (nath2024mechanismsofcblmediated pages 1-3)
- RING finger: binds E2 enzymes and is required for ubiquitin transfer to substrates. (ren2024theroleof pages 1-2, duan2003cblmediatedubiquitinylationis pages 1-1)
- C-terminal interaction motifs: proline-rich and ubiquitin-associated features (prominent in c-Cbl and Cbl-b) support assembly of signaling complexes and ubiquitin binding. (zutshi2024cblandcblb pages 1-2, nath2024mechanismsofcblmediated pages 1-3)
A representative schematic of domain architecture and ubiquitin-transfer mechanism is shown in Nath & Isakov 2024 (Life) (Figure 1). (nath2024mechanismsofcblmediated media 211be9ea)
c-Cbl catalyzes transfer of ubiquitin from an E2~ubiquitin conjugate to lysine residues on substrate proteins (E3 ubiquitin ligase activity), leading to mono- or polyubiquitination with downstream consequences (endocytosis/endosomal sorting, lysosomal degradation, proteasomal degradation, or signaling rewiring depending on context). (ren2024theroleof pages 1-2, nath2024mechanismsofcblmediated pages 1-3)
Cbl’s substrate specificity is largely context- and phosphorylation-dependent:
- Direct recognition via TKB/TKBD binding to phosphotyrosines on activated receptors/proteins. (nath2024mechanismsofcblmediated pages 1-3, duan2003cblmediatedubiquitinylationis pages 1-1)
- Indirect recruitment through adaptors (e.g., Grb2 linking EGFR to Cbl via Grb2 SH2–pEGFR and Grb2 SH3–Cbl proline-rich interactions). (duan2003cblmediatedubiquitinylationis pages 1-1)
Receptor tyrosine kinases (RTKs)
- EGFR is a canonical substrate/target: Cbl-mediated ubiquitination is required for efficient lysosomal sorting/degradation of EGFR after ligand stimulation; direct binding can occur via EGFR pY1045 to the Cbl TKB domain, with an alternative Grb2-mediated route. (duan2003cblmediatedubiquitinylationis pages 1-1)
- Newer mechanistic refinement (2023): Cbl and Cbl-b can regulate EGFR using distinct interaction modes, where Cbl-b preferentially binds EGFR pY1045, while Cbl relies mainly on Grb2-dependent recruitment in the tested context. (pinillamacua2023cblandcblb pages 1-2)
Immune signaling proteins (T/NK cell context)
A 2024 immune-focused review summarizes that Cbl-family E3 ligases ubiquitinate and downregulate proximal signaling components including TCR/CD3 subunits, Src-family kinases Fyn and Lck, the adaptor LAT, and other pathway components in T and NK cells. (nath2024mechanismsofcblmediated pages 1-3)
Limitations: The retrieved 2023–2024 sources used here describe E2 recruitment conceptually through the RING domain but do not consistently specify a single dominant E2 partner for c-Cbl in vivo; therefore, E2 partner specificity is not asserted beyond “RING-mediated E2 recruitment.” (nath2024mechanismsofcblmediated pages 1-3, ren2024theroleof pages 1-2)
Cbl is regulated by autoinhibition, in which the inactive conformation restricts catalytic function until receptor engagement and phosphorylation relieve inhibition. A conserved linker-region regulatory tyrosine (classically discussed as Tyr371 in c-Cbl) is emphasized as a key activation switch in mechanistic summaries. (liyasova2015molecularpathwayscbl pages 1-2)
A 2024 PNAS study defined a mechanistic module in macrophages: CLR (Dectin-1/2) → Syk → BLNK phosphorylation leads to BLNK association with c-Cbl, which inhibits Fyn-mediated phosphorylation of c-Cbl (including phosphorylation at Y737 as reported) and reduces downstream cytoskeletal/migratory outputs. (yang2024blnknegativelyregulates pages 7-8, yang2024blnknegativelyregulates pages 1-2)
c-Cbl is best viewed as a cytosolic adaptor/E3 that is recruited to activated plasma-membrane signaling complexes and subsequently to endocytic/endosomal trafficking sites, where it ubiquitinates receptors and associated proteins to direct trafficking fate:
- In the EGFR system, Cbl-dependent ubiquitination is required for sorting from early endosomes toward lysosomal degradation (a key step distinct from initial endocytosis). (duan2003cblmediatedubiquitinylationis pages 1-1)
- In macrophages responding to fungal ligands, c-Cbl is linked to F-actin/podosome-associated structures and PI3K-associated cytoskeletal remodeling required for migration. (yang2024blnknegativelyregulates pages 6-7)
Cbl-family ubiquitination of activated RTKs (EGFR paradigm) is a central, experimentally grounded function that links phosphorylation-dependent recognition to endosomal sorting and receptor downregulation. (duan2003cblmediatedubiquitinylationis pages 1-1, pinillamacua2023cblandcblb pages 1-2)
A 2024 iScience mouse study concluded that c-Cbl and Cbl-b have overlapping essential roles in maintaining intestinal epithelial stem cells:
- Whole-body double knockout is embryonic lethal (functional redundancy). (zutshi2024cblandcblb pages 15-16)
- In an Lgr5+ ISC-specific inducible double knockout, loss of Cbl/Cbl-b caused a rapid decrease in Lgr5+ ISCs with an increase in Lgr5-low transit-amplifying-like cells, increased crypt proliferation/fission, and reduced Paneth cells, but without long-term adenoma development in that system. (zutshi2024cblandcblb pages 15-16)
These phenotypes are consistent with Cbl-family control of growth-factor/cytokine signaling intensity (e.g., Akt–mTOR pathway readouts reported in the study). (zutshi2024cblandcblb pages 15-16)
The 2024 PNAS study supports a role for c-Cbl in macrophage podosome organization and migration, affecting host defense:
- Myeloid c-Cbl-deficient mice (Lyz2Cre/+ c-Cbl fl/fl) had increased susceptibility to systemic Candida albicans infection and reduced infiltration of Ly6C+ macrophages into kidneys. (yang2024blnknegativelyregulates pages 6-7)
- Mechanistically, BLNK modulated c-Cbl phosphorylation and PI3K-associated actin remodeling, linking c-Cbl to cytoskeletal outputs required for renal macrophage recruitment. (yang2024blnknegativelyregulates pages 7-8)
A 2023 study showed that even for a canonical substrate like EGFR, Cbl and Cbl-b can operate independently via different receptor-binding modes, and the impact of E3-dead mutants can be cell-context dependent (e.g., relative abundance of endogenous Cbl-b). (pinillamacua2023cblandcblb pages 1-2)
Two 2024 mouse studies extend functional annotation beyond classic RTK/immune-proximal signaling:
- Epithelial stem cell maintenance (intestinal crypt biology). (zutshi2024cblandcblb pages 15-16)
- CLR-driven innate immunity and migration during fungal infection. (yang2024blnknegativelyregulates pages 6-7)
A 2024 EMBO Molecular Medicine study connected PD-1/LAG-3 “dysfunction” signatures to negative regulation of the TCR signalosome and enrichment in ubiquitin ligase pathways, highlighting CBL-family ligases as actionable nodes. (chocarro2024pd1lag3cosignalingprofiling pages 1-2)
The strongest “real-world implementation” currently is pharmacologic targeting of CBL-family regulation in T cells, mainly via CBL-B inhibition as a means to increase T-cell activation.
In preclinical mouse studies reported in EMBO Molecular Medicine (2024), the authors tested anti-PD-1 + anti-LAG-3 with a CBL-B inhibitor in a Lacun3 lung adenocarcinoma model described as refractory to immunotherapy. They report dosing schedules (CBL-B inhibitor 10–30 mg/kg; antibodies 100 µg i.p. schedules) and claim that triple therapy “more than tripled survival” in a tested regimen; they also report n = 6 mice/group for in vivo cohorts. (chocarro2024pd1lag3cosignalingprofiling pages 10-12)
ClinicalTrials.gov includes a first-in-human, multicenter Phase 1a/1b study of NX-1607 (a CBL-B inhibitor) in adults with advanced malignancies:
- Identifier: NCT05107674 (https://clinicaltrials.gov/study/NCT05107674)
- Sponsor: Nurix Therapeutics, Inc.
- Start date: 2021-09-29
- Status: Recruiting
- Enrollment: 345
- Design: oral NX-1607 monotherapy and combination arms (including paclitaxel), with primary endpoints focused on safety/MTD and Phase 1b ORR. (NCT05107674 chunk 1)
The EMBO Molecular Medicine paper also explicitly references ongoing clinical evaluation of CBL-B inhibitors including NCT05662397 (https://clinicaltrials.gov/study/NCT05662397) in the context of combination strategies. (chocarro2024pd1lag3cosignalingprofiling pages 10-12)
Important scope note: These programs are primarily CBL-B-directed; nevertheless, the mechanistic foundation (CBL-family E3 ligases controlling phosphotyrosine-driven signaling thresholds) is shared with c-Cbl/Cbl and informs functional annotation and pathway-level applications. (ren2024theroleof pages 1-2, nath2024mechanismsofcblmediated pages 1-3, chocarro2024pd1lag3cosignalingprofiling pages 1-2)
Although the present report focuses on mouse c-Cbl, recent mechanistic summaries emphasize that CBL mutations are recurrent in hematologic malignancies and motivate therapeutic interest in CBL-pathway modulation. A recent mechanistic account reports that CBL mutations occur in ~5% of myeloid leukemias overall, and in 15–20% of JMML and ~15% of CMML. (tench2026targetingcblubiquitin pages 1-5)
The best-supported “core functional annotation” for mouse c-Cbl (P22682) is:
1) A phosphorylation-activated RING E3 ubiquitin ligase that recognizes activated signaling proteins via its TKBD and ubiquitinates them via RING-mediated E2 recruitment. (nath2024mechanismsofcblmediated pages 1-3, ren2024theroleof pages 1-2)
2) A central negative-feedback regulator of receptor signaling by linking receptor activation to ubiquitin-dependent receptor trafficking and degradation (EGFR archetype). (duan2003cblmediatedubiquitinylationis pages 1-1)
3) A context-dependent signaling rheostat in immune and myeloid cells, where adaptor networks (e.g., BLNK/Fyn/PI3K in CLR signaling) tune c-Cbl phosphorylation state and thereby cytoskeletal/migratory behavior and host defense. (yang2024blnknegativelyregulates pages 7-8, yang2024blnknegativelyregulates pages 6-7)
4) Functionally redundant with Cbl-b in specific tissues such that combined loss reveals essential roles in tissue homeostasis (intestinal stem cell maintenance). (zutshi2024cblandcblb pages 15-16)
| Aspect | Key evidence/findings (concise) | Primary citations (pqac ids) |
|---|---|---|
| Reaction/Function | Mouse c-Cbl (Cbl; UniProt P22682) matches the canonical CBL-family RING-type E3 ubiquitin ligase/adaptor: it recognizes phosphotyrosine-containing targets through its TKB/TKBD and recruits E2 enzymes through its RING domain to catalyze mono- or polyubiquitination, typically promoting receptor downregulation, endosomal sorting, lysosomal degradation, or altered signaling output. A classic well-established function is negative regulation of activated RTKs such as EGFR. | (ren2024theroleof pages 1-2, pinillamacua2023cblandcblb pages 1-2, duan2003cblmediatedubiquitinylationis pages 1-1, nath2024mechanismsofcblmediated pages 1-3) |
| Key domains | Core domain architecture is conserved and matches UniProt/domain annotations: N-terminal TKBD/TKB composed of a 4-helix bundle, EF-hand-like region, and SH2-like phosphotyrosine-recognition module; linker helix region (LHR); catalytic RING finger; plus C-terminal proline-rich region and UBA/leucine zipper features in c-Cbl/CBL-b. | (zutshi2024cblandcblb pages 1-2, nath2024mechanismsofcblmediated pages 1-3, ren2024theroleof pages 1-2, nath2024mechanismsofcblmediated media 211be9ea) |
| Regulation | c-Cbl is autoinhibited in its basal state; activation occurs after recruitment to active tyrosine kinases and phosphorylation of the linker-region regulatory tyrosine (classically Tyr371 in c-Cbl), which relieves autoinhibition and enables productive ubiquitin transfer. Adaptor binding can also modulate activation, and recent work highlights BLNK/Fyn/Syk control of c-Cbl phosphorylation in macrophages. | (tench2026targetingcblubiquitin pages 16-19, liyasova2015molecularpathwayscbl pages 1-2, yang2024blnknegativelyregulates pages 7-8, yang2024blnknegativelyregulates pages 1-2) |
| Representative substrates | Best-established substrates/targets include activated EGFR/RTKs; immune signaling proteins such as TCR/CD3 subunits, ZAP70-associated complexes, Src-family kinases Fyn and Lck, LAT, and C3G are also described for Cbl-family signaling control. For EGFR specifically, Cbl and Cbl-b can bind by distinct mechanisms, with c-Cbl relying mainly on Grb2-dependent recruitment in some cell contexts. | (pinillamacua2023cblandcblb pages 1-2, duan2003cblmediatedubiquitinylationis pages 1-1, nath2024mechanismsofcblmediated pages 1-3) |
| Pathways/cell types | c-Cbl is most firmly placed in RTK downregulation and immune receptor signaling. Established settings include EGFR trafficking/signaling, TCR/NK-cell signaling, cytokine/Src-family kinase pathways, intestinal epithelial stem-cell homeostasis, and CLR/Syk/Fyn/PI3K signaling in macrophages responding to fungal ligands. | (ren2024theroleof pages 1-2, nath2024mechanismsofcblmediated pages 1-3, yang2024blnknegativelyregulates pages 7-8, zutshi2024cblandcblb pages 15-16) |
| Cellular localization | Functional activity is context dependent: c-Cbl is cytosolic/adaptor-like at baseline, then recruited to activated membrane receptor complexes, clathrin-associated/endosomal trafficking machinery, and signaling assemblies where it promotes receptor ubiquitination, internalization, intraluminal vesicle sorting, and lysosomal targeting. In macrophages it also associates with F-actin/podosome-related structures during migration signaling. | (pinillamacua2023cblandcblb pages 1-2, duan2003cblmediatedubiquitinylationis pages 1-1, yang2024blnknegativelyregulates pages 7-8, yang2024blnknegativelyregulates pages 6-7) |
| Mouse phenotypes 2024 iScience & 2024 PNAS | In intestine, c-Cbl and Cbl-b are partly redundant: ISC-specific inducible double loss caused rapid depletion of Lgr5+ stem cells, increase in Lgr5-low transit-amplifying-like cells, increased crypt proliferation/fission, altered differentiation, and reduced Paneth cells; whole-body double knockout is embryonic lethal. In myeloid cells, c-Cbl promoted macrophage migration/podosome organization and kidney Ly6C+ macrophage infiltration during Candida infection; myeloid c-Cbl deficiency increased susceptibility to systemic candidiasis. | (zutshi2024cblandcblb pages 15-16, yang2024blnknegativelyregulates pages 6-7, yang2024blnknegativelyregulates pages 1-2) |
| Translational/therapeutic angles 2024 EMBO Mol Med & clinical trials | A 2024 EMBO Mol Med study identified CBL-family ligases as immunotherapy-relevant nodes downstream of PD-1/LAG-3 dysfunction programs; combined checkpoint blockade plus CBL-B inhibition showed significant antitumor activity in a refractory mouse lung cancer model, with reports that triple therapy more than tripled survival in one regimen and required CD8 T cells. Clinically, CBL-B-directed agents are already in early trials, including NX-1607 (NCT05107674; phase 1, recruiting; planned enrollment 345) and HST-1011 (NCT05662397; phase 1/2, active not recruiting; enrollment 77), illustrating translational exploitation of the broader CBL pathway even though these programs mainly target CBL-B rather than c-Cbl itself. | (chocarro2024pd1lag3cosignalingprofiling pages 10-12, chocarro2024pd1lag3cosignalingprofiling pages 10-10, chocarro2024pd1lag3cosignalingprofiling pages 1-2) |
Table: This table summarizes the core functional annotation of mouse c-Cbl (Cbl; UniProt P22682), including its biochemical role, domains, regulation, representative substrates, localization, mouse phenotypes, and translational relevance. It is useful as a compact evidence map linking recent 2023-2024 findings to established mechanistic literature.
A domain-and-mechanism schematic for CBL-family ubiquitination (Figure 1) is available from Nath & Isakov 2024 (Life). (nath2024mechanismsofcblmediated media 211be9ea)
References
(zutshi2024cblandcblb pages 1-2): Neha Zutshi, Bhopal Mohapatra, Pinaki Mondal, Wei An, Benjamin T. Goetz, Shuo Wang, Sicong Li, Matthew D. Storck, David F. Mercer, Adrian Black, Sarah P. Thayer, Jennifer D. Black, Chi Lin, Vimla Band, and Hamid Band. Cbl and cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance. iScience, May 2024. URL: https://doi.org/10.1016/j.isci.2024.109912, doi:10.1016/j.isci.2024.109912. This article has 5 citations and is from a peer-reviewed journal.
(nath2024mechanismsofcblmediated pages 1-3): Pulak Ranjan Nath and Noah Isakov. Mechanisms of cbl-mediated ubiquitination of proteins in t and natural killer cells and effects on immune cell functions. Life, 14:1592, Dec 2024. URL: https://doi.org/10.3390/life14121592, doi:10.3390/life14121592. This article has 2 citations.
(ren2024theroleof pages 1-2): Jiaqi Ren, Linlin Lv, Xufeng Tao, Xiaohan Zhai, Xuyang Chen, Hao Yu, Xinya Zhao, Xin Kong, Zhan Yu, Deshi Dong, and Jing Liu. The role of cbl family ubiquitin ligases in cancer progression and therapeutic strategies. Frontiers in Pharmacology, Jul 2024. URL: https://doi.org/10.3389/fphar.2024.1432545, doi:10.3389/fphar.2024.1432545. This article has 12 citations.
(duan2003cblmediatedubiquitinylationis pages 1-1): Lei Duan, Yuko Miura, Manjari Dimri, Biswanath Majumder, Ingrid L. Dodge, Alagarsamy L. Reddi, Amiya Ghosh, Norvin Fernandes, Pengcheng Zhou, Karen Mullane-Robinson, Navin Rao, Stephen Donoghue, Rick A. Rogers, David Bowtell, Mayumi Naramura, Hua Gu, Vimla Band, and Hamid Band. Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth factor receptor but is dispensable for endocytosis*. Journal of Biological Chemistry, 278:28950-28960, Aug 2003. URL: https://doi.org/10.1074/jbc.m304474200, doi:10.1074/jbc.m304474200. This article has 169 citations and is from a domain leading peer-reviewed journal.
(nath2024mechanismsofcblmediated media 211be9ea): Pulak Ranjan Nath and Noah Isakov. Mechanisms of cbl-mediated ubiquitination of proteins in t and natural killer cells and effects on immune cell functions. Life, 14:1592, Dec 2024. URL: https://doi.org/10.3390/life14121592, doi:10.3390/life14121592. This article has 2 citations.
(pinillamacua2023cblandcblb pages 1-2): Itziar Pinilla-Macua and Alexander Sorkin. Cbl and cbl-b independently regulate egfr through distinct receptor interaction modes. Molecular Biology of the Cell, Dec 2023. URL: https://doi.org/10.1091/mbc.e23-02-0058, doi:10.1091/mbc.e23-02-0058. This article has 26 citations and is from a domain leading peer-reviewed journal.
(liyasova2015molecularpathwayscbl pages 1-2): Mariya S. Liyasova, Ke Ma, and Stanley Lipkowitz. Molecular pathways: cbl proteins in tumorigenesis and antitumor immunity—opportunities for cancer treatment. Clinical Cancer Research, 21:1789-1794, Apr 2015. URL: https://doi.org/10.1158/1078-0432.ccr-13-2490, doi:10.1158/1078-0432.ccr-13-2490. This article has 86 citations and is from a highest quality peer-reviewed journal.
(yang2024blnknegativelyregulates pages 7-8): Yi-Heng Yang, Ke-Fang Xie, Shuai Yang, Huan Wang, Hui-Hui Ma, Min Zhou, Zhong-Wei Wang, Yebo Gu, and Xin-Ming Jia. Blnk negatively regulates innate antifungal immunity through inhibiting c-cbl-mediated macrophage migration. Proceedings of the National Academy of Sciences of the United States of America, Oct 2024. URL: https://doi.org/10.1073/pnas.2400920121, doi:10.1073/pnas.2400920121. This article has 8 citations and is from a highest quality peer-reviewed journal.
(yang2024blnknegativelyregulates pages 1-2): Yi-Heng Yang, Ke-Fang Xie, Shuai Yang, Huan Wang, Hui-Hui Ma, Min Zhou, Zhong-Wei Wang, Yebo Gu, and Xin-Ming Jia. Blnk negatively regulates innate antifungal immunity through inhibiting c-cbl-mediated macrophage migration. Proceedings of the National Academy of Sciences of the United States of America, Oct 2024. URL: https://doi.org/10.1073/pnas.2400920121, doi:10.1073/pnas.2400920121. This article has 8 citations and is from a highest quality peer-reviewed journal.
(yang2024blnknegativelyregulates pages 6-7): Yi-Heng Yang, Ke-Fang Xie, Shuai Yang, Huan Wang, Hui-Hui Ma, Min Zhou, Zhong-Wei Wang, Yebo Gu, and Xin-Ming Jia. Blnk negatively regulates innate antifungal immunity through inhibiting c-cbl-mediated macrophage migration. Proceedings of the National Academy of Sciences of the United States of America, Oct 2024. URL: https://doi.org/10.1073/pnas.2400920121, doi:10.1073/pnas.2400920121. This article has 8 citations and is from a highest quality peer-reviewed journal.
(zutshi2024cblandcblb pages 15-16): Neha Zutshi, Bhopal Mohapatra, Pinaki Mondal, Wei An, Benjamin T. Goetz, Shuo Wang, Sicong Li, Matthew D. Storck, David F. Mercer, Adrian Black, Sarah P. Thayer, Jennifer D. Black, Chi Lin, Vimla Band, and Hamid Band. Cbl and cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance. iScience, May 2024. URL: https://doi.org/10.1016/j.isci.2024.109912, doi:10.1016/j.isci.2024.109912. This article has 5 citations and is from a peer-reviewed journal.
(chocarro2024pd1lag3cosignalingprofiling pages 1-2): Luisa Chocarro, Ester Blanco, Leticia Fernandez-Rubio, Maider Garnica, Miren Zuazo, Maria Jesus Garcia, Ana Bocanegra, Miriam Echaide, Colette Johnston, Carolyn J Edwards, James Legg, Andrew J Pierce, Hugo Arasanz, Gonzalo Fernandez-Hinojal, Ruth Vera, Karina Ausin, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Grazyna Kochan, and David Escors. Pd-1/lag-3 co-signaling profiling uncovers cbl ubiquitin ligases as key immunotherapy targets. EMBO Molecular Medicine, 16:1791-1816, Jul 2024. URL: https://doi.org/10.1038/s44321-024-00098-y, doi:10.1038/s44321-024-00098-y. This article has 18 citations and is from a highest quality peer-reviewed journal.
(chocarro2024pd1lag3cosignalingprofiling pages 10-12): Luisa Chocarro, Ester Blanco, Leticia Fernandez-Rubio, Maider Garnica, Miren Zuazo, Maria Jesus Garcia, Ana Bocanegra, Miriam Echaide, Colette Johnston, Carolyn J Edwards, James Legg, Andrew J Pierce, Hugo Arasanz, Gonzalo Fernandez-Hinojal, Ruth Vera, Karina Ausin, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Grazyna Kochan, and David Escors. Pd-1/lag-3 co-signaling profiling uncovers cbl ubiquitin ligases as key immunotherapy targets. EMBO Molecular Medicine, 16:1791-1816, Jul 2024. URL: https://doi.org/10.1038/s44321-024-00098-y, doi:10.1038/s44321-024-00098-y. This article has 18 citations and is from a highest quality peer-reviewed journal.
(NCT05107674 chunk 1): A Study of NX-1607 in Adults With Advanced Malignancies. Nurix Therapeutics, Inc.. 2021. ClinicalTrials.gov Identifier: NCT05107674
(tench2026targetingcblubiquitin pages 1-5): Andrea J. Tench, Claire E. Martin, Craig D. Simpson, Leanne E. Wybenga-Groot, Diane Ly, Christopher Fladd, Melissa H. Elgie, Syed F. Ahmed, Roger Belizaire, Danny T. Huang, Anne-Claude Gingras, and C. Jane McGlade. Targeting cbl ubiquitin ligase activation to downregulate tyrosine kinase signalling. bioRxiv, Mar 2026. URL: https://doi.org/10.64898/2026.03.16.712190, doi:10.64898/2026.03.16.712190. This article has 0 citations.
(tench2026targetingcblubiquitin pages 16-19): Andrea J. Tench, Claire E. Martin, Craig D. Simpson, Leanne E. Wybenga-Groot, Diane Ly, Christopher Fladd, Melissa H. Elgie, Syed F. Ahmed, Roger Belizaire, Danny T. Huang, Anne-Claude Gingras, and C. Jane McGlade. Targeting cbl ubiquitin ligase activation to downregulate tyrosine kinase signalling. bioRxiv, Mar 2026. URL: https://doi.org/10.64898/2026.03.16.712190, doi:10.64898/2026.03.16.712190. This article has 0 citations.
(chocarro2024pd1lag3cosignalingprofiling pages 10-10): Luisa Chocarro, Ester Blanco, Leticia Fernandez-Rubio, Maider Garnica, Miren Zuazo, Maria Jesus Garcia, Ana Bocanegra, Miriam Echaide, Colette Johnston, Carolyn J Edwards, James Legg, Andrew J Pierce, Hugo Arasanz, Gonzalo Fernandez-Hinojal, Ruth Vera, Karina Ausin, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Grazyna Kochan, and David Escors. Pd-1/lag-3 co-signaling profiling uncovers cbl ubiquitin ligases as key immunotherapy targets. EMBO Molecular Medicine, 16:1791-1816, Jul 2024. URL: https://doi.org/10.1038/s44321-024-00098-y, doi:10.1038/s44321-024-00098-y. This article has 18 citations and is from a highest quality peer-reviewed journal.
id: P22682
gene_symbol: Cbl
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:10090
label: Mus musculus
description: Cbl is a RING-type E3 ubiquitin-protein ligase and phosphotyrosine-binding adaptor
that recognizes activated receptor tyrosine kinases and other signaling proteins. It ubiquitinates
receptors and signaling components to promote endocytosis, lysosomal or proteasomal turnover,
and negative feedback on EGFR, PDGFRA, KIT, CSF1R, SRC-family, and immune-receptor signaling
pathways.
existing_annotations:
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: plasma membrane is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0007165
label: signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: signal transduction is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0045121
label: membrane raft
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: membrane raft is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0030971
label: receptor tyrosine kinase binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: receptor tyrosine kinase binding is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0001784
label: phosphotyrosine residue binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: phosphotyrosine residue binding is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0004842
label: ubiquitin-protein transferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: ubiquitin-protein transferase activity is directly supported as part of the core
molecular function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: calcium ion binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: cytoplasm is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: Golgi apparatus is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: plasma membrane is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005929
label: cilium
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
supported_by:
- reference_id: PMID:29237719
supporting_text: c-Cbl becomes enriched in the cilium, and the receptor is subsequently
ubiquitinated and internalized
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0007166
label: cell surface receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: cell surface receptor signaling pathway is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0008270
label: zinc ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: zinc ion binding is too generic or indirect for Cbl; the evidence supports a
more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016740
label: transferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: The annotation captures a real aspect of Cbl biology, but transferase activity
is less precise than GO:0061630 ubiquitin protein ligase activity for this gene.
action: MODIFY
reason: Use a more specific GO term supported by the gene product role
proposed_replacement_terms:
- id: GO:0061630
label: ubiquitin protein ligase activity
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0023051
label: regulation of signaling
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: The annotation captures a real aspect of Cbl biology, but regulation of signaling
is less precise than GO:0042059 negative regulation of epidermal growth factor receptor
signaling pathway for this gene.
action: MODIFY
reason: Use a more specific GO term supported by the gene product role
proposed_replacement_terms:
- id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0046872
label: metal ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: metal ion binding is too generic or indirect for Cbl; the evidence supports a
more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:1902531
label: regulation of intracellular signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: The annotation captures a real aspect of Cbl biology, but regulation of intracellular
signal transduction is less precise than GO:0042059 negative regulation of epidermal
growth factor receptor signaling pathway for this gene.
action: MODIFY
reason: Use a more specific GO term supported by the gene product role
proposed_replacement_terms:
- id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:2000583
label: regulation of platelet-derived growth factor receptor-alpha signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: regulation of platelet-derived growth factor receptor-alpha signaling pathway
is directly supported as part of the core molecular function, direct pathway role, or
primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12559036
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:12559036
supporting_text: CD2AP/CMS regulates endosome morphology and traffic to the degradative
pathway through its interaction with Rab4 and c-Cbl.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23374343
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:23374343
supporting_text: Induction of Siglec-G by RNA viruses inhibits the innate immune response
by promoting RIG-I degradation.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23799367
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:23799367
supporting_text: Threshold-controlled ubiquitination of the EGFR directs receptor fate.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24440350
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:24440350
supporting_text: 2014 Jan 17. Targeting of the MET receptor tyrosine kinase by small
molecule inhibitors leads to MET accumulation by impairing the receptor downregulation.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:27474268
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:27474268
supporting_text: Co-recruitment analysis of the CBL and CBLB signalosomes in primary
T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:7657591
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:7657591
supporting_text: Tyrosine phosphorylation of the c-cbl proto-oncogene protein product
and association with epidermal growth factor (EGF) receptor upon EGF stimulation.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:9890970
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:9890970
supporting_text: Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding
site for phosphatidylinositol 3-kinase.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0000209
label: protein polyubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein polyubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005925
label: focal adhesion
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: focal adhesion is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: ubiquitin-dependent protein catabolic process is directly supported as part of
the core molecular function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006513
label: protein monoubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein monoubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006974
label: DNA damage response
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: DNA damage response is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0008584
label: male gonad development
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: male gonad development is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0010332
label: response to gamma radiation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: response to gamma radiation is biologically plausible for Cbl but represents
a context-specific pathway, localization, interaction, phenotype, or downstream response
rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0014823
label: response to activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: response to activity is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: protein ubiquitination is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0017124
label: SH3 domain binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein kinase binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0030424
label: axon
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: axon is biologically plausible for Cbl but represents a context-specific pathway,
localization, interaction, phenotype, or downstream response rather than the primary
core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0030426
label: growth cone
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: growth cone is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0033574
label: response to testosterone
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: response to testosterone is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0036120
label: cellular response to platelet-derived growth factor stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: cellular response to platelet-derived growth factor stimulus is biologically
plausible for Cbl but represents a context-specific pathway, localization, interaction,
phenotype, or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0036312
label: phosphatidylinositol 3-kinase regulatory subunit binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: phosphatidylinositol 3-kinase regulatory subunit binding is biologically plausible
for Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042594
label: response to starvation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: response to starvation is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: negative regulation of apoptotic process is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0043303
label: mast cell degranulation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: mast cell degranulation is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0045471
label: response to ethanol
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: response to ethanol is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0046875
label: ephrin receptor binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0048260
label: positive regulation of receptor-mediated endocytosis
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: positive regulation of receptor-mediated endocytosis is directly supported as
part of the core molecular function, direct pathway role, or primary localization of
Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: perinuclear region of cytoplasm is biologically plausible for Cbl but represents
a context-specific pathway, localization, interaction, phenotype, or downstream response
rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050821
label: protein stabilization
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein stabilization is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050860
label: negative regulation of T cell receptor signaling pathway
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: negative regulation of T cell receptor signaling pathway is biologically plausible
for Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050868
label: negative regulation of T cell activation
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: negative regulation of T cell activation is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0051865
label: protein autoubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein autoubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is biologically plausible for Cbl but represents a context-specific pathway,
localization, interaction, phenotype, or downstream response rather than the primary
core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0070534
label: protein K63-linked ubiquitination
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling
receptors, but the available evidence does not establish K63 linkage specificity.
action: MODIFY
reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
proposed_replacement_terms:
- id: GO:0016567
label: protein ubiquitination
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0071456
label: cellular response to hypoxia
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: cellular response to hypoxia is biologically plausible for Cbl but represents
a context-specific pathway, localization, interaction, phenotype, or downstream response
rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:1990090
label: cellular response to nerve growth factor stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: cellular response to nerve growth factor stimulus is biologically plausible for
Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: protein tyrosine kinase binding is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Golgi apparatus is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: plasma membrane is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005929
label: cilium
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
supported_by:
- reference_id: PMID:29237719
supporting_text: c-Cbl becomes enriched in the cilium, and the receptor is subsequently
ubiquitinated and internalized
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: ubiquitin-dependent protein catabolic process is directly supported as part of
the core molecular function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: protein ubiquitination is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0017124
label: SH3 domain binding
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: negative regulation of apoptotic process is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0046875
label: ephrin receptor binding
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0048260
label: positive regulation of receptor-mediated endocytosis
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: positive regulation of receptor-mediated endocytosis is directly supported as
part of the core molecular function, direct pathway role, or primary localization of
Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050821
label: protein stabilization
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: protein stabilization is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050860
label: negative regulation of T cell receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: negative regulation of T cell receptor signaling pathway is biologically plausible
for Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050868
label: negative regulation of T cell activation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: negative regulation of T cell activation is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
transduction is biologically plausible for Cbl but represents a context-specific pathway,
localization, interaction, phenotype, or downstream response rather than the primary
core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0070534
label: protein K63-linked ubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling
receptors, but the available evidence does not establish K63 linkage specificity.
action: MODIFY
reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
proposed_replacement_terms:
- id: GO:0016567
label: protein ubiquitination
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0097229
label: sperm end piece
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: sperm end piece is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0000209
label: protein polyubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: protein polyubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005925
label: focal adhesion
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: focal adhesion is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006513
label: protein monoubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: protein monoubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0017124
label: SH3 domain binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: protein kinase binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0030424
label: axon
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: axon is biologically plausible for Cbl but represents a context-specific pathway,
localization, interaction, phenotype, or downstream response rather than the primary
core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0030426
label: growth cone
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: growth cone is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0036312
label: phosphatidylinositol 3-kinase regulatory subunit binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: phosphatidylinositol 3-kinase regulatory subunit binding is biologically plausible
for Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: negative regulation of apoptotic process is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: perinuclear region of cytoplasm is biologically plausible for Cbl but represents
a context-specific pathway, localization, interaction, phenotype, or downstream response
rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0051865
label: protein autoubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: protein autoubiquitination is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: protein tyrosine kinase binding is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9763892
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050821
label: protein stabilization
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: protein stabilization is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050860
label: negative regulation of T cell receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: negative regulation of T cell receptor signaling pathway is biologically plausible
for Cbl but represents a context-specific pathway, localization, interaction, phenotype,
or downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0050868
label: negative regulation of T cell activation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: negative regulation of T cell activation is biologically plausible for Cbl but
represents a context-specific pathway, localization, interaction, phenotype, or downstream
response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0070534
label: protein K63-linked ubiquitination
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Cbl is well supported as an E3 ubiquitin ligase that ubiquitinates signaling
receptors, but the available evidence does not establish K63 linkage specificity.
action: MODIFY
reason: Use a broader ubiquitination term because the chain-linkage specificity is unsupported
proposed_replacement_terms:
- id: GO:0016567
label: protein ubiquitination
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:12754251
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:12754251
supporting_text: 2003 May 18. Cbl-mediated ubiquitinylation is required for lysosomal
sorting of epidermal growth factor receptor but is dispensable for endocytosis.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IMP
original_reference_id: PMID:15962011
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:15962011
supporting_text: Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth
factor receptor downregulation.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:15383614
review:
summary: plasma membrane is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:15383614
supporting_text: Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that
involves the ubiquitin-interacting motif of Eps15.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: ISO
original_reference_id: PMID:11823423
review:
summary: protein ubiquitination is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:11823423
supporting_text: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils
a role for Grb2 in negative signaling.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IGI
original_reference_id: PMID:11823423
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:11823423
supporting_text: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils
a role for Grb2 in negative signaling.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IGI
original_reference_id: PMID:11823423
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:11823423
supporting_text: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils
a role for Grb2 in negative signaling.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IMP
original_reference_id: PMID:12754251
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:12754251
supporting_text: 2003 May 18. Cbl-mediated ubiquitinylation is required for lysosomal
sorting of epidermal growth factor receptor but is dispensable for endocytosis.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0070086
label: ubiquitin-dependent endocytosis
evidence_type: ISO
original_reference_id: PMID:11823423
review:
summary: ubiquitin-dependent endocytosis is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:11823423
supporting_text: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils
a role for Grb2 in negative signaling.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: IMP
original_reference_id: PMID:23457600
review:
summary: ubiquitin-dependent protein catabolic process is directly supported as part of
the core molecular function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: IDA
original_reference_id: PMID:23457600
review:
summary: protein ubiquitination is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:23457600
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:23457600
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IDA
original_reference_id: PMID:15383614
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:15383614
supporting_text: Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that
involves the ubiquitin-interacting motif of Eps15.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IDA
original_reference_id: PMID:23457600
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0061630
label: ubiquitin protein ligase activity
evidence_type: IMP
original_reference_id: PMID:23457600
review:
summary: ubiquitin protein ligase activity is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:23457600
supporting_text: Berberine inhibits proliferation and down-regulates epidermal growth
factor receptor through activation of Cbl in colon tumor cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0070086
label: ubiquitin-dependent endocytosis
evidence_type: IMP
original_reference_id: PMID:15383614
review:
summary: ubiquitin-dependent endocytosis is directly supported as part of the core molecular
function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:15383614
supporting_text: Sep 21. c-Cbl directs EGF receptors into an endocytic pathway that
involves the ubiquitin-interacting motif of Eps15.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016600
label: flotillin complex
evidence_type: IDA
original_reference_id: PMID:11001060
review:
summary: flotillin complex is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: PMID:11001060
supporting_text: CAP defines a second signalling pathway required for insulin-stimulated
glucose transport.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:9447983
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:9447983
supporting_text: A novel, multifuntional c-Cbl binding protein in insulin receptor signaling
in 3T3-L1 adipocytes.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9680646
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9680706
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9682158
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9682182
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9763891
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9763892
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9817994
review:
summary: cytosol is directly supported as part of the core molecular function, direct
pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: protein ubiquitination is directly supported as part of the core molecular function,
direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0032487
label: regulation of Rap protein signal transduction
evidence_type: IMP
original_reference_id: PMID:12671687
review:
summary: regulation of Rap protein signal transduction is biologically plausible for Cbl
but represents a context-specific pathway, localization, interaction, phenotype, or
downstream response rather than the primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: PMID:12671687
supporting_text: Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IDA
original_reference_id: PMID:29237719
review:
summary: The cited study supports IFT20/Golgi effects on ciliary PDGFR signaling and Cbl
stability, but does not directly establish Cbl as a Golgi-localized gene product.
action: REMOVE
reason: Cited evidence does not support this gene-product annotation
- term:
id: GO:0005929
label: cilium
evidence_type: IDA
original_reference_id: PMID:29237719
review:
summary: Cbl has evidence for ciliary enrichment during PDGFRalpha feedback regulation, but this is a specialized signaling context rather than the primary localization or core E3 ligase function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role. Cbl's core function is ubiquitination of activated receptors/adaptors; ciliary localization occurs in the IFT20/PDGFRalpha signaling context.
supported_by:
- reference_id: PMID:29237719
supporting_text: c-Cbl becomes enriched in the cilium, and the receptor is subsequently
ubiquitinated and internalized
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:2000583
label: regulation of platelet-derived growth factor receptor-alpha signaling pathway
evidence_type: IMP
original_reference_id: PMID:29237719
review:
summary: regulation of platelet-derived growth factor receptor-alpha signaling pathway
is directly supported as part of the core molecular function, direct pathway role, or
primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: PMID:29237719
supporting_text: Dec 13. IFT20 modulates ciliary PDGFRα signaling by regulating the
stability of Cbl E3 ubiquitin ligases.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:8551236
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:8551236
supporting_text: Association of tyrosine protein kinase Zap-70 with the protooncogene
product p120c-cbl in T lymphocytes.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21830225
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:21830225
supporting_text: Aug 9. SH3KBP1-binding protein 1 prevents epidermal growth factor receptor
degradation by the interruption of c-Cbl-CIN85 complex.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006511
label: ubiquitin-dependent protein catabolic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: ubiquitin-dependent protein catabolic process is directly supported as part of
the core molecular function, direct pathway role, or primary localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: negative regulation of epidermal growth factor receptor signaling pathway is
directly supported as part of the core molecular function, direct pathway role, or primary
localization of Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0048260
label: positive regulation of receptor-mediated endocytosis
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: positive regulation of receptor-mediated endocytosis is directly supported as
part of the core molecular function, direct pathway role, or primary localization of
Cbl.
action: ACCEPT
reason: Directly supported core function, process, or location
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11152963
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:11152963
supporting_text: SETA is a multifunctional adapter protein with three SH3 domains that
binds Grb2, Cbl, and the novel SB1 proteins.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16455755
review:
summary: protein binding is too generic or indirect for Cbl; the evidence supports a more
specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:16455755
supporting_text: Spatial and temporal regulation of GLUT4 translocation by flotillin-1
and caveolin-3 in skeletal muscle cells.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0046875
label: ephrin receptor binding
evidence_type: IPI
original_reference_id: PMID:18034775
review:
summary: ephrin receptor binding is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: PMID:18034775
supporting_text: 2007 Dec 19. Ligand binding induces Cbl-dependent EphB1 receptor degradation
through the lysosomal pathway.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: CBL is phosphorylated by tyrosine kinases but is not itself a protein kinase;
the direct catalytic role is ubiquitin transfer.
action: REMOVE
reason: Annotation conflicts with known molecular function or domain architecture
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0045453
label: bone resorption
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: bone resorption is biologically plausible for Cbl but represents a context-specific
pathway, localization, interaction, phenotype, or downstream response rather than the
primary core function.
action: KEEP_AS_NON_CORE
reason: Supported secondary or context-specific role
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- term:
id: GO:0017124
label: SH3 domain binding
evidence_type: IPI
original_reference_id: PMID:9447983
review:
summary: SH3 domain binding is too generic or indirect for Cbl; the evidence supports
a more specific signaling, catalytic, adaptor, or localization role.
action: MARK_AS_OVER_ANNOTATED
reason: Overly broad or uninformative relative to the supported core function
supported_by:
- reference_id: PMID:9447983
supporting_text: A novel, multifuntional c-Cbl binding protein in insulin receptor signaling
in 3T3-L1 adipocytes.
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors.
Recognizes activated receptor tyrosine kinases and mediates their ubiquitination to
terminate signaling. CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating
enzyme to acceptor protein lysine. DOMAIN: The RING-type zinc finger domain mediates
binding to an E2 ubiquitin-conjugating enzyme; the N-terminus includes a phosphotyrosine
binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
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:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
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:0000096
title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat
orthologs
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs
using Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000119
title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human
orthologs
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:11001060
title: CAP defines a second signalling pathway required for insulin-stimulated glucose transport.
findings: []
- id: PMID:11152963
title: SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2,
Cbl, and the novel SB1 proteins.
findings: []
- id: PMID:11823423
title: A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role
for Grb2 in negative signaling.
findings: []
- id: PMID:12559036
title: CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through
its interaction with Rab4 and c-Cbl.
findings: []
- id: PMID:12671687
title: Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase.
findings: []
- id: PMID:12754251
title: Cbl-mediated ubiquitinylation is required for lysosomal sorting of epidermal growth
factor receptor but is dispensable for endocytosis.
findings: []
- id: PMID:15383614
title: c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting
motif of Eps15.
findings: []
- id: PMID:15962011
title: Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor
downregulation.
findings: []
- id: PMID:16455755
title: Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3
in skeletal muscle cells.
findings: []
- id: PMID:18034775
title: Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal
pathway.
findings: []
- id: PMID:21830225
title: SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by
the interruption of c-Cbl-CIN85 complex.
findings: []
- id: PMID:23374343
title: Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting
RIG-I degradation.
findings: []
- id: PMID:23457600
title: Berberine inhibits proliferation and down-regulates epidermal growth factor receptor
through activation of Cbl in colon tumor cells.
findings: []
- id: PMID:23799367
title: Threshold-controlled ubiquitination of the EGFR directs receptor fate.
findings: []
- id: PMID:24440350
title: Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads
to MET accumulation by impairing the receptor downregulation.
findings: []
- id: PMID:27474268
title: Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies
CD5 as a key regulator of TCR-induced ubiquitylation.
findings: []
- id: PMID:29237719
title: IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin
ligases.
findings: []
- id: PMID:7657591
title: Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association
with epidermal growth factor (EGF) receptor upon EGF stimulation.
findings: []
- id: PMID:8551236
title: Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl
in T lymphocytes.
findings: []
- id: PMID:9447983
title: A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1
adipocytes.
findings: []
- id: PMID:9890970
title: Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for
phosphatidylinositol 3-kinase.
findings: []
- id: Reactome:R-MMU-9680646
title: Pik3r11:Pik3ca,b,d (Pi3k), Plcg2 (PLCgamma2), Grb2:Sos1, Shc1 (Shc), Ptpn11 (Shp2),
Grb2:Gab2, Grb2:Gab3, Grap2 (MONA), Cbl:Grb2, Inpp5d (SHIP1), Inppl1 (SHIP2) bind p-8Y-Csf1r
and are activated
findings: []
- id: Reactome:R-MMU-9680706
title: Csf1r trans-autophosphorylates on multiple tyrosine residues
findings: []
- id: Reactome:R-MMU-9682158
title: Csf1r-associated Plcg2 hydrolyzes phosphatidylcholine yielding choline phosphate
and 1,2-diacylglycerol
findings: []
- id: Reactome:R-MMU-9682182
title: Csf1r-associated PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate
findings: []
- id: Reactome:R-MMU-9763891
title: Src family kinases phosphorylate Cbl in Csf1 dimer:p-Y559-Csf1r dimer:Cbl
findings: []
- id: Reactome:R-MMU-9763892
title: p-Y-Cbl autoubiquitinates and multiubiquitinates p-Y-559-Csf12
findings: []
- id: Reactome:R-MMU-9817994
title: Csf1 dimer:p-Y559-Csf1r dimer:Fyn,Hck,Src,Yes1 binds Cbl
findings: []
- id: UniProt:P22682
title: UniProt record for Cbl (P22682)
findings: []
- id: file:mouse/Cbl/Cbl-deep-research-falcon.md
title: Deep research report on Cbl (falcon)
findings: []
core_functions:
- molecular_function:
id: GO:0061630
label: ubiquitin protein ligase activity
description: Transfers ubiquitin to activated receptor tyrosine kinases and signaling substrates
to attenuate signaling and promote receptor downregulation.
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005886
label: plasma membrane
directly_involved_in:
- id: GO:0016567
label: protein ubiquitination
- id: GO:0042059
label: negative regulation of epidermal growth factor receptor signaling pathway
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes
activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling.
CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor
protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating
enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
- molecular_function:
id: GO:0030971
label: receptor tyrosine kinase binding
description: The TKB/phosphotyrosine-binding region recognizes activated receptor tyrosine
kinases, positioning the RING E3 ligase domain for substrate ubiquitination.
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005886
label: plasma membrane
directly_involved_in:
- id: GO:0070086
label: ubiquitin-dependent endocytosis
supported_by:
- reference_id: UniProt:P22682
supporting_text: 'FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
of many signaling pathways by mediating ubiquitination of cell surface receptors. Recognizes
activated receptor tyrosine kinases and mediates their ubiquitination to terminate signaling.
CATALYTIC ACTIVITY: transfers ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor
protein lysine. DOMAIN: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating
enzyme; the N-terminus includes a phosphotyrosine binding/TKB domain.'
- reference_id: file:mouse/Cbl/Cbl-deep-research-falcon.md
supporting_text: Falcon deep research report reviewed for GO term specificity, core-function
context, and evidence synthesis.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []