CBL (c-Cbl) is a cytoplasmic RING-type ubiquitin E3 ligase and signaling adaptor that is recruited to activated tyrosine-kinase complexes. Its N-terminal tyrosine kinase-binding module recognizes selected phosphotyrosine motifs, while a linker and RING domain recruit an E2 ubiquitin-conjugating enzyme; Tyr371 phosphorylation helps relieve autoinhibition. Its proline-rich region binds SH3-domain adaptors, and phosphorylated CBL can itself recruit SH2-domain partners. CBL ubiquitinates receptors and associated signaling proteins, contributing to receptor trafficking and attenuation of growth-factor signals. Ubiquitination can also regulate signaling without accelerating degradation: CBL and CBLB redundantly modify ligand-engaged LAG3, enabling its inhibitory activity in T cells. CBL can act through noncatalytic interactions as well, with context-dependent effects on survival signaling. It acts in the cytosol and on the cytoplasmic side of membrane-associated complexes. Germline CBL variants cause a Noonan-like disorder with variable predisposition to juvenile myelomonocytic leukemia; disease-associated linker/RING variants can disrupt ubiquitination and receptor trafficking.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000209 protein polyubiquitination | IEA GO_REF:0000107 | ACCEPT | Summary: Retain polyubiquitination as an executed CBL process. Reason: CBL catalyses ubiquitin-chain assembly rather than merely being a substrate of it. The human LAG3 study provides an independent target basis, including CBL/CBLB double-loss and individual rescue and K63-chain controls. The original rat/Ensembl transfer is preserved; its specific donor experiment was not independently reconstructed. |
| GO:0001784 phosphotyrosine residue binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain phosphotyrosine recognition by the TKB domain. Reason: The domain prediction agrees with CBL phosphopeptide structures and binding measurements in PMID:18273061 and PMID:22266821. This is CBL recognizing phosphorylated residues on a ligand; it is distinct from other proteins recognizing phosphorylated CBL. Positive target-peptide results do not imply that every tested receptor peptide binds. |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Retain the broad ubiquitin-transferase activity. Reason: The RING-domain mapping agrees with the experimentally established E3 activity in PMID:10514377 and PMID:22266821. CBL recruits and activates an E2; the broad parent does not imply that CBL forms a HECT-like catalytic thioester. The existing, more informative E3 assertion supplies the core function. |
| GO:0004842 ubiquitin-protein transferase activity | TAS PMID:15465819 Ubiquitin ligase activity of c-Cbl guides the epidermal grow... | ACCEPT | Summary: Retain ubiquitin-transferase activity in EGFR trafficking. Reason: The source links CBL ligase activity to Eps15 recruitment and ligand-bound EGFR entry into coated pits. This agrees with independent direct E3 evidence; it does not assign the catalytic activity of E2 or EGFR to CBL. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-182986 | ACCEPT | Summary: Retain the curated CBL ubiquitination reaction. Reason: The complete cached Reactome summary identifies CBL-mediated ubiquitination in the specified reaction. This supports the broad transferase parent, with E3 activity already represented separately. Reaction context is preserved rather than treating every receptor or adaptor as an interchangeable substrate. Supporting Evidence: Reactome:R-HSA-182986 |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-182993 | ACCEPT | Summary: Retain the curated CBL ubiquitination reaction. Reason: The complete cached Reactome summary identifies CBL-mediated ubiquitination in the specified reaction. This supports the broad transferase parent, with E3 activity already represented separately. Reaction context is preserved rather than treating every receptor or adaptor as an interchangeable substrate. Supporting Evidence: Reactome:R-HSA-182993 |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-183084 | ACCEPT | Summary: Retain the curated CBL ubiquitination reaction. Reason: The complete cached Reactome summary identifies CBL-mediated ubiquitination in the specified reaction. This supports the broad transferase parent, with E3 activity already represented separately. Reaction context is preserved rather than treating every receptor or adaptor as an interchangeable substrate. Supporting Evidence: Reactome:R-HSA-183084 |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-183089 | ACCEPT | Summary: Retain the curated CBL ubiquitination reaction. Reason: The complete cached Reactome summary identifies CBL-mediated ubiquitination in the specified reaction. This supports the broad transferase parent, with E3 activity already represented separately. Reaction context is preserved rather than treating every receptor or adaptor as an interchangeable substrate. Supporting Evidence: Reactome:R-HSA-183089 |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain structural calcium binding as non-core. Reason: The reviewed UniProt record records the calcium-binding site within the TKB architecture, consistent with the EF-hand region and structural literature. This supports bound calcium without making CBL a calcium sensor or a calcium-channel regulator. |
| GO:0005515 protein binding | IPI PMID:10068674 Cloning and characterization of a lymphoid-specific, inducib... | KEEP AS NON CORE | Summary: Retain the CBLβPTPN22 association as non-core. Reason: The complete PMID:10068674 abstract supports complex formation with the lymphoid tyrosine phosphatase. It does not make CBL a phosphatase or establish CBL recognizing a phosphorylated residue on PTPN22. Retain the qualitative interaction under the project binding policy; the exact binary interface is not resolved here. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10092522 The proto-oncogene p120(Cbl) is a downstream substrate of th... | MODIFY | Summary: Refine binding to the HCK tyrosine kinase. Reason: PMID:10092522 describes the CBLβHCK complex and kinase-dependent CBL phosphorylation. This supports binding to a protein tyrosine kinase, not CBL kinase activity or recognition of phosphoserine. Preserve the original P08631-2 tested-product identity; no isoform-exclusive mechanism is claimed. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:10092522 the interaction between Cbl and Hck is direct |
| GO:0005515 protein binding | IPI PMID:10679202 Cloning and characterization of a novel adaptor protein, CIN... | MODIFY | Summary: Refine the CIN85 association to SH3-domain binding. Reason: The complete PMID:10679202 abstract identifies CIN85 SH3-domain-dependent association with the CBL proline-rich region. The recognized domain belongs to CIN85; CBL supplies its binding sequence. Independent structural work in PMID:15090612 and PMID:19268472 corroborates this direction. Proposed replacements: SH3 domain binding |
| GO:0005515 protein binding | IPI PMID:11157475 SHP2 and cbl participate in alpha-chemokine receptor CXCR4-m... | MODIFY | Summary: Refine the 14-3-3 beta association. Reason: PMID:11157475 supports CBL association with 14-3-3 beta. The partner is the phosphoserine-binding adaptor; phosphorylation of CBL is not evidence that CBL recognizes phosphoserine. The informative own activity is binding the 14-3-3 protein. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:11157475 association of cbl with PI-3 kinase, Crk-L, and 14-3-3beta proteins |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAQ (14-3-3 theta/tau) interaction to 14-3-3 protein binding. Reason: The exact P27348 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAB (14-3-3 beta/alpha) interaction to 14-3-3 protein binding. Reason: The exact P31946 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβSFN (14-3-3 sigma) interaction to 14-3-3 protein binding. Reason: The exact P31947 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAG (14-3-3 gamma) interaction to 14-3-3 protein binding. Reason: The exact P61981 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAE (14-3-3 epsilon) interaction to 14-3-3 protein binding. Reason: The exact P62258 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAZ (14-3-3 zeta/delta) interaction to 14-3-3 protein binding. Reason: The exact P63104 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad... | MODIFY | Summary: Refine the supported CBLβYWHAH (14-3-3 eta) interaction to 14-3-3 protein binding. Reason: The exact Q04917 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The complete abstract explicitly reports CBL binding by multiple 14-3-3 family members; the exact individual pair-level experiment was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11891219 A novel Src homology 2 domain-containing molecule, Src-like ... | KEEP AS NON CORE | Summary: Retain SLAP2 association as non-core. Reason: PMID:11891219 describes CBL recruitment in the SLAP2 signaling-adaptor context. This supports an association but does not identify which domain of the intact partner is contacted by CBL in the inspected abstract. Retain generic binding rather than infer SH2- or SH3-domain recognition solely from the partner architecture. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12177062 CIN85 participates in Cbl-b-mediated down-regulation of rece... | KEEP AS NON CORE | Summary: Retain the CIN85 association with the target-assay limit explicit. Reason: The PMID:12177062 abstract foregrounds Cbl-b, so it cannot by itself establish the exact CBL construct in the original experiment. That does not demonstrate miscitation. The same CBLβCIN85 association has independent primary support in PMID:10679202 and PMID:15090612; retain the qualitative edge without pretending that the original target panel was read. |
| GO:0005515 protein binding | IPI PMID:12815057 Tyrosine phosphorylation of Sprouty2 enhances its interactio... | MODIFY | Summary: Refine SPRY2 recognition to phosphotyrosine binding. Reason: PMID:12815057 describes tyrosine-phosphorylation-dependent SPRY2 recognition by the CBL TKB region, with Tyr55 central to the interaction. CBL is the reader of the SPRY2 phosphotyrosine motif; the specific activity is supported independently by the CBLβSPRY2 peptide structure in PMID:18273061. Proposed replacements: phosphotyrosine residue binding |
| GO:0005515 protein binding | IPI PMID:14596919 Dab2 links CIN85 with clathrin-mediated receptor internaliza... | KEEP AS NON CORE | Summary: Retain CIN85 binding without transferring the DAB2 interface. Reason: PMID:14596919 foregrounds DAB2βCIN85 mechanisms. The inspected abstract does not locate a CBL-specific interface in that experiment; the CBLβCIN85 edge is independently supported by PMID:10679202 and PMID:15090612. Retain the generic association while keeping the original assay boundary explicit. |
| GO:0005515 protein binding | IPI PMID:15090612 CIN85 associates with multiple effectors controlling intrace... | MODIFY | Summary: Refine CIN85 binding to recognition of its SH3 domain. Reason: PMID:15090612 directly maps CBL proline/arginine-containing motifs engaging CIN85 SH3 domains. This is domain binding by CBL, not CBL possessing an SH3 domain. The mapped interface supports the refinement. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:15090612 CIN85 src homology 3 domains specifically bind to a proline-arginine |
| GO:0005515 protein binding | IPI PMID:15094368 Engagement of beta2 integrins recruits 14-3-3 proteins to c-... | MODIFY | Summary: Refine 14-3-3 theta association. Reason: The complete PMID:15094368 abstract supports CBLβ14-3-3 association. CBL is the phosphorylated ligand in this mechanism; binding a 14-3-3 protein is the informative activity and does not confer the partnerβs phosphoserine-recognition function on CBL. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:15094368 phosphorylation associated with the scaffolding and anti-apoptotic 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:15282549 LRIG1 restricts growth factor signaling by enhancing recepto... | KEEP AS NON CORE | Summary: Retain LRIG1 association as non-core. Reason: PMID:15282549 supports CBL recruitment in the LRIG1/EGFR downregulation complex. Recruitment and coassociation support this generic edge without proving a purified binary interface or transferring LRIG1 membrane-receptor properties to CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15657067 Phosphotyrosine signaling networks in epidermal growth facto... | KEEP AS NON CORE | Summary: Retain the screen-derived EGFR association. Reason: The original PMID:15657067 pair-level assay was not independently recovered. The exact curated EGFR edge is corroborated in UniProt and by target-specific CBLβEGFR binding experiments in PMID:7657591. Retain qualitative binding under the project policy without claiming that the screen table was inspected. |
| GO:0005515 protein binding | IPI PMID:15708858 c-Cbl mediates ubiquitination, degradation, and down-regulat... | KEEP AS NON CORE | Summary: Retain proteinase-activated receptor 2 association as non-core. Reason: PMID:15708858 describes the CBL-containing receptor complex and CBL RING-dependent receptor trafficking. This supports association in that context, not a protease activity of CBL or an independently demonstrated purified receptorβCBL binary contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15737992 Structural characterization of a novel Cbl phosphotyrosine r... | MODIFY | Summary: Refine APS recognition to phosphotyrosine binding. Reason: PMID:15737992 directly investigates binding of the CBL TKB domain to phosphorylated APS sequences. The activity is CBL recognition of the partner phosphotyrosine motif, not the reverse SH2-domain interaction. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:15737992 phosphopeptide interaction with the Cbl TKB domain |
| GO:0005515 protein binding | IPI PMID:15962011 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epiderma... | MODIFY | Summary: Refine SPRY2 recognition to phosphotyrosine binding. Reason: The PMID:15962011 signaling-complex result is consistent with the directly mapped CBL TKBβSPRY2 phosphotyrosine interface in PMID:12815057 and PMID:18273061. This independent same-partner evidence supports the specific recognition activity without assigning every ternary-complex effect to CBL alone. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:12815057 phosphorylation on tyrosine 55, is required |
| GO:0005515 protein binding | IPI PMID:15962011 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epiderma... | MODIFY | Summary: Refine EGFR binding to receptor tyrosine kinase binding. Reason: PMID:15962011 places CBL in the EGFR/SPRY2/CIN85 complex. Independent target-specific receptor binding in PMID:7657591 establishes the same EGFR edge. Binding an RTK is supported; neither receptor catalytic activity nor a unique direct interface in every complex is transferred to CBL. Proposed replacements: receptor tyrosine kinase binding |
| GO:0005515 protein binding | IPI PMID:15962011 Sprouty2 acts at the Cbl/CIN85 interface to inhibit epiderma... | MODIFY | Summary: Refine CIN85 association using the independently mapped SH3 interface. Reason: The source PMID:15962011 describes the signaling complex, while PMID:15090612 directly maps the same CBLβCIN85 contact to CIN85 SH3 domains. This supports CBL SH3-domain binding without treating the complex-level result alone as domain mapping. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:15090612 CIN85 src homology 3 domains specifically bind to a proline-arginine |
| GO:0005515 protein binding | IPI PMID:16407834 Cbl escapes Cdc42-mediated inhibition by downregulation of t... | MODIFY | Summary: Refine beta-PIX association to SH3-domain binding. Reason: PMID:16407834 maps beta-PIX SH3-mediated association with CBL. The domain belongs to the partner, making SH3-domain binding the relevant recognition activity; CBL is not assigned beta-PIX exchange-factor activity. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:16407834 the SH3 domain of betaPix specifically interacts |
| GO:0005515 protein binding | IPI PMID:16407834 Cbl escapes Cdc42-mediated inhibition by downregulation of t... | KEEP AS NON CORE | Summary: Retain CIN85 coassociation in the beta-PIX context. Reason: PMID:16407834 concerns recruitment and competition within the CBL/beta-PIX/CIN85 system. The qualitative CIN85 edge is also independently supported by PMID:15090612. Retain this context-specific association without equating complex assembly with a new catalytic activity. |
| GO:0005515 protein binding | IPI PMID:16467851 Recruitment and activation of PLCgamma1 in T cells: a new in... | KEEP AS NON CORE | Summary: Retain the recorded xenolog PLCG1 interaction. Reason: PMID:16467851 supports PLCG1βCBL association. The machine partner P08487 is retained exactly and UniProt labels this interaction as xenologous. Neither a human-only construct assignment nor CBL phospholipase activity is inferred from the generic edge. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16636290 Targeting AMAP1 and cortactin binding bearing an atypical sr... | KEEP AS NON CORE | Summary: Retain SRC association in the AMAP1 signaling context. Reason: PMID:16636290 foregrounds AMAP1-associated signaling, and the exact CBL target interface is not fully exposed in the abstract. The SRCβCBL association is independently supported by PMID:17094785 and the curated interaction record. Retain the qualitative edge without asserting that the original complex experiment maps a binary contact. |
| GO:0005515 protein binding | IPI PMID:16893902 A Src homology 3-binding sequence on the C terminus of Sprou... | KEEP AS NON CORE | Summary: Retain SPRY2 association with the original source limit. Reason: PMID:16893902 foregrounds GRB2-dependent SPRY2 signaling. The inspected abstract does not independently resolve its exact CBL experiment; the same CBLβSPRY2 association is directly supported by PMID:12815057. Retain generic binding without substituting a GRB2 interface for a CBL interface. |
| GO:0005515 protein binding | IPI PMID:16914641 Intersectin regulates epidermal growth factor receptor endoc... | MODIFY | Summary: Refine EGFR association to receptor tyrosine kinase binding. Reason: PMID:16914641 places EGFR and CBL in an intersectin-regulated complex, and PMID:7657591 independently establishes CBLβEGFR recognition. The binding partner is an RTK; this does not imply CBL receptor or kinase activity. Proposed replacements: receptor tyrosine kinase binding |
| GO:0005515 protein binding | IPI PMID:16914641 Intersectin regulates epidermal growth factor receptor endoc... | MODIFY | Summary: Refine intersectin binding to SH3-domain binding. Reason: PMID:16914641 maps the CBLβintersectin interaction to the partnerβs SH3 domains. CBL provides a proline-rich ligand; the domain-recognition direction therefore supports SH3-domain binding. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:16914641 Src homology (SH) 3 domains binding to the Pro-rich COOH terminus of Cbl |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | MODIFY | Summary: Refine p85 association to PI3K regulatory-subunit binding. Reason: PMID:16982329 reports p85 in the CBL-associated signaling complex. Independent biochemical mapping of the same p85 interaction in PMID:9160881 and PMID:9890970 supports regulatory-subunit binding. The catalytic PI3K function is not assigned to CBL. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: PMID:9160881 p85 interacts with the proline-rich domain of Cbl |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | KEEP AS NON CORE | Summary: Retain JNK1 coassociation as non-core. Reason: PMID:16982329 supports a CBL-associated signaling complex containing JNK. Coimmunoprecipitation does not by itself identify a purified binary kinase contact or establish that CBL catalyses phosphorylation; retain the generic association. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | KEEP AS NON CORE | Summary: Retain CRKL coassociation as non-core. Reason: PMID:16982329 supports CRKL within a CBL-associated complex. It does not make phosphorylated CBL a phosphotyrosine reader in that particular edge. Retain the qualitative association; domain-specific evidence from other CRKL studies is kept distinct. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17020880 Atypical polyproline recognition by the CMS N-terminal Src h... | KEEP AS NON CORE | Summary: Retain CD2AP association without transferring the paralog peptide structure. Reason: PMID:17020880 studies a Cbl-b-derived peptide with the adaptor domain, so that structure alone does not establish an identical CBL contact. The exact CBLβCD2AP association is corroborated by the reviewed UniProt interaction record. Preserve qualitative binding and the original target-assay uncertainty; do not infer a wrong-gene annotation from the title. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17094785 Identification and functional characterization of an Src hom... | MODIFY | Summary: Refine SRC association to SH3-domain binding. Reason: PMID:17094785 directly investigates the CBL proline-rich sequence engaging the SRC SH3 domain. This is CBL binding a domain on SRC; it does not confer SRC kinase activity on CBL. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17094785 of Src binding to proline-rich sequences of Cbl |
| GO:0005515 protein binding | IPI PMID:17094785 Identification and functional characterization of an Src hom... | MODIFY | Summary: Refine the proline-rich CBLβGRB2 interaction to SH3 domain binding. Reason: Newly inspected original PMID:17094785 Results report that CBL peptide 494 competes for GST-GRB2 association, while the SRC-preferring peptide 540 has little effect; the former result is described as data not shown. Fig. 4 uses 293-VnR lysate pull-downs. Independent PMID:11997436 GST-SH3 and GRB2 deletion experiments establish the partner-domain direction. CBL supplies a proline-rich ligand for GRB2 SH3 domains; this does not transfer the distinct SRC site or claim an all-purified binary assay. Proposed replacements: SH3 domain binding |
| GO:0005515 protein binding | IPI PMID:17141222 PI3-kinase/Akt-dependent antiapoptotic signaling by the PDGF... | KEEP AS NON CORE | Summary: Retain SRC association with the original assay limit explicit. Reason: PMID:17141222 does not expose the complete CBL-specific experiment in the inspected abstract. The same SRCβCBL edge is independently supported by PMID:17094785 and UniProt. Retain the generic association without a new claim about the original construct or interface. |
| GO:0005515 protein binding | IPI PMID:17372230 A critical role for the E3-ligase activity of c-Cbl in VEGFR... | KEEP AS NON CORE | Summary: Retain the exact xenolog PLCG1 association. Reason: PMID:17372230 describes constitutive PLCG1βCBL coassociation. The source partner F1SDV6 is preserved and the reviewed interaction record identifies xenologous evidence. This supports a bounded association, not an assumed human partner or a phospholipase activity of CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17395426 Abi-1 forms an epidermal growth factor-inducible complex wit... | MODIFY | Summary: Refine ABI1-2 association to SH3-domain binding. Reason: PMID:17395426 maps the ABI1 interaction with CBL using the partnerβs SH3 region. The exact Q8IZP0-2 product identity remains unchanged; testing that product does not establish isoform exclusivity. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:17395426 an Abi-1 mutant lacking the SH3 domain (DeltaSH3) fails to interact with Cbl |
| GO:0005515 protein binding | IPI PMID:17974561 Tesk1 interacts with Spry2 to abrogate its inhibition of ERK... | MODIFY | Summary: Refine SPRY2 recognition to phosphotyrosine binding. Reason: The CBL/SPRY2 ubiquitination context in PMID:17974561 is consistent with the directly established CBL TKBβSPRY2 phosphotyrosine interface in PMID:12815057 and PMID:18273061. The refinement concerns the same binding partner and does not transfer SPRY2 regulatory activity to CBL. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:12815057 phosphorylation on tyrosine 55, is required |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 Figure 5A directly measures APS phosphopeptide binding to CBL-TKB by isothermal titration calorimetry, including a pH-dependent comparison; Figure 4G also tests full-length CBL with rat myc-tagged APS and IR-B using a mutational binding assay. Independent PMID:15737992 supplies the CBL TKBβAPS phosphopeptide structure and additional calorimetry. Together these establish CBL recognition of the partner phosphotyrosine motif. The exact machine partner remains unchanged, and the rat whole-protein construct is distinguished from the human annotation. Proposed replacements: phosphotyrosine residue binding |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:18273061 complexed with phosphorylated peptides |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:18273061 complexed with phosphorylated peptides |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:18273061 complexed with phosphorylated peptides |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:17094785 binding of the tyrosine kinase-binding domain to the Src phosphotyrosine 416 |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | UNDECIDED | Summary: The FLT1-specific binding assertion remains unresolved. Reason: Newly inspected original PMID:18273061 Results and Fig. 5 report no measurable binding of the wild-type phosphorylated VEGFR1 peptide under the tested conditions; engineered V1331N/L1332R substitutions restore binding. That is not evidence that the native FLT1 peptide shares the positive interface mapped for the other partners. The original annotation may refer to a different construct or assay not resolved here. Preserve uncertainty without claiming that intact FLT1 can never associate with CBL or inventing a residue-loss analysis. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:18273061 complexed with phosphorylated peptides |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:18273061 Fig. 4H reports endogenous GRB2 co-immunoprecipitation with full-length CBL and TKB mutants in 293T cells. This control supports association but does not isolate the GRB2 contact domain; TKB peptide structures from other partners are not transferred to GRB2. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:18273061 Structural basis for a novel intrapeptidyl H-bond and revers... | MODIFY | Summary: Refine the assayed partner phosphopeptide recognition. Reason: PMID:18273061 experimentally tests CBL TKB recognition of the recorded partnerβs phosphorylated peptide, using structural and/or binding measurements. This supports CBL phosphotyrosine-residue binding. The construct-level evidence is not a claim that every intact receptor interaction uses only this motif or that every partner peptide tested in the paper was positive. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:18273061 complexed with phosphorylated peptides |
| GO:0005515 protein binding | IPI PMID:18654987 Identification of multi-SH3 domain-containing protein intera... | KEEP AS NON CORE | Summary: Retain intersectin association from the interaction screen. Reason: The exact PMID:18654987 target-screen table was not independently recovered. UniProt corroborates the same edge and PMID:16914641 independently supports CBLβintersectin association. Retain qualitative binding while preserving the original screen-access limit. |
| GO:0005515 protein binding | IPI PMID:19268472 Novel insights into the mechanisms of CIN85 SH3 domains bind... | MODIFY | Summary: Refine CIN85 association to SH3-domain binding. Reason: The complete PMID:19268472 abstract describes structural recognition of CBL and CBLB proline-rich peptides by CIN85 SH3 domains. CBL recognition of the partner domain is supported without collapsing the two paralogs or assigning CBL an SH3 domain. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:19268472 CIN85A and CIN85B binding to proline-arginine peptides |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | KEEP AS NON CORE | Summary: Retain the exact curated signaling-network association. Reason: PMID:19380743 is a phosphotyrosine-dependent interaction-network study. The exact partner edge is corroborated in the reviewed CBL interaction record, but the original pair-level assay and binding direction were not independently resolved. Phosphorylated CBL recruiting another protein does not establish CBL phosphotyrosine recognition in this row. Retain generic binding without a stronger interface claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | KEEP AS NON CORE | Summary: Retain the exact curated signaling-network association. Reason: PMID:19380743 is a phosphotyrosine-dependent interaction-network study. The exact partner edge is corroborated in the reviewed CBL interaction record, but the original pair-level assay and binding direction were not independently resolved. Phosphorylated CBL recruiting another protein does not establish CBL phosphotyrosine recognition in this row. Retain generic binding without a stronger interface claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | KEEP AS NON CORE | Summary: Retain the exact curated signaling-network association. Reason: PMID:19380743 is a phosphotyrosine-dependent interaction-network study. The exact partner edge is corroborated in the reviewed CBL interaction record, but the original pair-level assay and binding direction were not independently resolved. Phosphorylated CBL recruiting another protein does not establish CBL phosphotyrosine recognition in this row. Retain generic binding without a stronger interface claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19380743 Charting the molecular network of the drug target Bcr-Abl. | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:19380743 profiles BCR-ABL-associated complexes by affinity purification and mass spectrometry in K562 cells. The original CBLβGRB2 target record and interface remain uninspected; this is not the separate kinase-assisted two-hybrid study. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:20308550 The phosphatase and tensin homolog regulates epidermal growt... | MODIFY | Summary: Refine EGFR association to receptor tyrosine kinase binding. Reason: PMID:20308550 describes CBL recruitment to activated EGFR, with direct target-specific receptor recognition independently established in PMID:7657591. This supports the partner-class refinement while retaining the distinction between receptor binding, ubiquitination and trafficking outcomes. Proposed replacements: receptor tyrosine kinase binding |
| GO:0005515 protein binding | IPI PMID:20562913 Differential roles of ERK and Akt pathways in regulation of ... | KEEP AS NON CORE | Summary: Retain EGFR association with source-specific uncertainty. Reason: The original PMID:20562913 target panel was not independently recovered. The exact curated EGFR edge and independent PMID:7657591 binding evidence support qualitative retention; they do not establish the construct or interface used in the unavailable original panel. |
| GO:0005515 protein binding | IPI PMID:20618440 Proteomic and biochemical analysis of 14-3-3-binding protein... | MODIFY | Summary: Refine the supported CBLβYWHAZ (14-3-3 zeta/delta) interaction to 14-3-3 protein binding. Reason: The exact P63104 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original interaction-study pair-level assay was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20711168 A Dyn2-CIN85 complex mediates degradative traffic of the EGF... | KEEP AS NON CORE | Summary: Retain CIN85 association in the dynamin signaling context. Reason: PMID:20711168 foregrounds dynamin-associated signaling; the exact CBL-specific interface in that paper was not independently recovered. The CBLβCIN85 association has independent support in PMID:15090612 and PMID:19268472, supporting qualitative retention without claiming the original panel was verified. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:20936779 supplies a human MAPK interaction map. The original CBLβGRB2 construct and pair-level result were not independently recovered. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:21163258 An adjacent arginine, and the phosphorylated tyrosine in the... | MODIFY | Summary: Refine MET recognition to phosphotyrosine binding. Reason: PMID:21163258 describes the METβCBL recognition site, corroborated by the CBL TKBβMET peptide structure in PMID:18273061. CBL recognizes the phosphorylated receptor motif; it does not acquire MET kinase activity. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:21163258 Met) binds to the c-Cbl phosphotyrosine-recognition |
| GO:0005515 protein binding | IPI PMID:21570973 Ligand-induced downregulation of TrkA is partly regulated th... | MODIFY | Summary: Refine TrkA association to receptor tyrosine kinase binding. Reason: PMID:21570973 describes phosphorylated TrkA association with CBL and receptor ubiquitination. This supports binding to the RTK partner without implying that receptor phosphorylation is catalysed by CBL. Proposed replacements: receptor tyrosine kinase binding Supporting Evidence: PMID:21570973 direct interactions between c-Cbl and phosphorylated TrkA |
| GO:0005515 protein binding | IPI PMID:21706016 Selected reaction monitoring mass spectrometry reveals the d... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:21706016 measures growth-factor-dependent GRB2 complexes in HEK293T cells by AP-SRM. Its exact CBL record and any corresponding domain comparison were not independently inspected; no APS recruitment claim is made. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:22266821 Structural basis for autoinhibition and phosphorylation-depe... | MODIFY | Summary: Refine ZAP70 phosphopeptide recognition. Reason: Selected original PMID:22266821 structures use a ZAP70 phosphopeptide bound to the CBL TKB region. This directly supports phosphotyrosine recognition by CBL. The human CBL fragment and purified structural context are distinguished from full-length signaling complexes in cells. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:22266821 TKBD alone or bound to ZAP-70 peptide |
| GO:0005515 protein binding | IPI PMID:22266821 Structural basis for autoinhibition and phosphorylation-depe... | MODIFY | Summary: Refine UBE2D2 binding to ubiquitin-conjugating-enzyme binding. Reason: PMID:22266821 directly assays UbcH5B/UBE2D2 binding to CBL using structures and surface plasmon resonance, with GST controls and CBL phosphorylation/mutant comparisons. CBL binds the E2 while providing RING E3 activity; it is not itself assigned the E2 conjugating activity. Proposed replacements: ubiquitin conjugating enzyme binding Supporting Evidence: PMID:22266821 enhanced E2-binding module |
| GO:0005515 protein binding | IPI PMID:23799367 Threshold-controlled ubiquitination of the EGFR directs rece... | MODIFY | Summary: Refine EGFR recruitment to RTK binding. Reason: PMID:23799367 describes cooperative CBL recruitment to phosphorylated EGFR in the presence of GRB2. This supports receptor tyrosine kinase binding while retaining the distinction between direct TKB recognition and adaptor-assisted recruitment. Proposed replacements: receptor tyrosine kinase binding Supporting Evidence: PMID:23799367 recruitment of the E3 ligase Cbl, in complex with Grb2, to the EGFR |
| GO:0005515 protein binding | IPI PMID:23799367 Threshold-controlled ubiquitination of the EGFR directs rece... | MODIFY | Summary: Refine GRB2-mediated receptor recruitment to the supported SH3-binding mechanism. Reason: PMID:23799367 reports cooperative CBL recruitment to EGFR, including GRB2 depletion and GRB2 addition in recruitment/ubiquitination assays. Independent PMID:11997436 directly tests GRB2 SH3-domain pull-downs and deletion constructs during CBL receptor recruitment, supplying the domain-specific mechanism used for this refinement. The 2013 recruitment result alone does not map the domain, and no purified binary-interface claim is made. This bounded recruitment interpretation is not imposed on unrelated unresolved GRB2 screening contexts. Proposed replacements: SH3 domain binding |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | MODIFY | Summary: Refine the supported CBLβYWHAB (14-3-3 beta/alpha) interaction to 14-3-3 protein binding. Reason: The exact P31946 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original pair-specific interaction panel was not independently recovered. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: Refine the supported CBLβYWHAE (14-3-3 epsilon) interaction to 14-3-3 protein binding. Reason: The exact P62258 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original proteostasis-network target table was not independently inspected; no chaperone function or substrate relationship is inferred. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:25036637 supplies a human proteostasis interaction network. The original CBLβGRB2 target table and binding interface remain uninspected; no chaperone role is assigned to CBL. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: Refine the supported CBLβYWHAH (14-3-3 eta) interaction to 14-3-3 protein binding. Reason: The exact Q04917 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original proteostasis-network target table was not independently inspected; no chaperone function or substrate relationship is inferred. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | KEEP AS NON CORE | Summary: Retain the exact curated proteostasis-interactome edge. Reason: PMID:25036637 provides interaction-network evidence and the reviewed CBL entry lists the exact source partner. The original target-specific table was not independently read. Under the standing binding policy this supports qualified non-core retention, not a new chaperone, catalytic or substrate activity for CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | KEEP AS NON CORE | Summary: Retain the exact curated proteostasis-interactome edge. Reason: PMID:25036637 provides interaction-network evidence and the reviewed CBL entry lists the exact source partner. The original target-specific table was not independently read. Under the standing binding policy this supports qualified non-core retention, not a new chaperone, catalytic or substrate activity for CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: Retain MET association in the proximity-assay context. Reason: PMID:25241761 uses a proximity-based assay; proximity alone does not map a binary interface. The same METβCBL edge is independently supported by PMID:18273061 and PMID:21163258. Retain the qualitative association without treating proximity as purified direct binding. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | KEEP AS NON CORE | Summary: Retain the exact phosphotyrosine-network association. Reason: PMID:25814554 and the reviewed UniProt record corroborate this partner edge. The original pair-level recognition direction was not independently resolved. In particular, another protein recognizing phosphorylated CBL is not evidence that CBL recognizes a phosphorylated residue on that partner. Retain generic binding with the target-table access limit explicit. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | KEEP AS NON CORE | Summary: Retain the exact phosphotyrosine-network association. Reason: PMID:25814554 and the reviewed UniProt record corroborate this partner edge. The original pair-level recognition direction was not independently resolved. In particular, another protein recognizing phosphorylated CBL is not evidence that CBL recognizes a phosphorylated residue on that partner. Retain generic binding with the target-table access limit explicit. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | KEEP AS NON CORE | Summary: Retain the exact phosphotyrosine-network association. Reason: PMID:25814554 and the reviewed UniProt record corroborate this partner edge. The original pair-level recognition direction was not independently resolved. In particular, another protein recognizing phosphorylated CBL is not evidence that CBL recognizes a phosphorylated residue on that partner. Retain generic binding with the target-table access limit explicit. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:25814554 studies phosphorylation-dependent interactions with a kinase-assisted two-hybrid approach. The exact CBLβGRB2 pair and its phosphorylation/domain dependence were not independently inspected; a domain mechanism from another target cannot be transferred. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | KEEP AS NON CORE | Summary: Retain the exact phosphotyrosine-network association. Reason: PMID:25814554 and the reviewed UniProt record corroborate this partner edge. The original pair-level recognition direction was not independently resolved. In particular, another protein recognizing phosphorylated CBL is not evidence that CBL recognizes a phosphorylated residue on that partner. Retain generic binding with the target-table access limit explicit. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27059931 Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA p... | MODIFY | Summary: Refine EGFR association to RTK binding. Reason: PMID:27059931 compares EGFR variant behavior with wild-type receptor and reports reduced CBL engagement for the variant. A reduced mutant interaction does not negate the positive wild-type association. The partner-class refinement is receptor tyrosine kinase binding, without assuming identical affinity across variants. Proposed replacements: receptor tyrosine kinase binding Supporting Evidence: PMID:27059931 EGFRvA binds less to E3 ubiquitin ligase c-Cbl than EGFR does |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Refine the supported CBLβYWHAG (14-3-3 gamma) interaction to 14-3-3 protein binding. Reason: The exact P61981 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original BioPlex target table was not independently inspected; an affinity association does not alone establish a purified binary interface. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:28514442 supplies BioPlex affinity-purification/mass-spectrometry association evidence. The original CBLβGRB2 target table and contact surface were not independently inspected. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Refine the supported CBLβYWHAH (14-3-3 eta) interaction to 14-3-3 protein binding. Reason: The exact Q04917 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original BioPlex target table was not independently inspected; an affinity association does not alone establish a purified binary interface. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain the exact BioPlex association as non-core. Reason: The PMID:28514442 source and UniProt list the exact interaction partner. The original BioPlex target-specific table was not independently recovered. Retain a qualified association under the project policy; affinity coassociation does not by itself establish direct contact, substrate identity or a new cellular process. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29237719 IFT20 modulates ciliary PDGFRΞ± signaling by regulating the s... | KEEP AS NON CORE | Summary: Retain CBLB coassociation in the IFT20 complex. Reason: Original PMID:29237719 Results report CBLB coimmunoprecipitation with FLAG-tagged human CBL constructs in HEK293T cells, with wild-type and RING-mutant comparisons. This supports association in the complex, not necessarily a purified binary heterodimer or identical functions of the two ligases. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29237719 IFT20 modulates ciliary PDGFRΞ± signaling by regulating the s... | KEEP AS NON CORE | Summary: Retain the CBLβIFT20 association. Reason: Original PMID:29237719 Results include FLAGβIFT20 affinity isolation and reciprocal endogenous coimmunoprecipitation with CBL in HEK293T cells. Only a fraction of IFT20 is associated with CBL; this does not establish that CBL is a constitutive component of every IFT-B complex or that the interaction is a purified binary contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | KEEP AS NON CORE | Summary: Retain the exact KRAS-network coassociation. Reason: PMID:31980649 supplies affinity-interaction-network evidence and UniProt corroborates the exact CBL partner. The original pair-level table remains uninspected. Retain qualitative association without transferring a KRAS phenotype, direct-contact mechanism or substrate status to CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:31980649 supplies a KRAS/EGFR network context. The original CBLβGRB2 target table and interface remain uninspected; the network context does not define CBL recognition of a GRB2 domain. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | KEEP AS NON CORE | Summary: Retain the exact KRAS-network coassociation. Reason: PMID:31980649 supplies affinity-interaction-network evidence and UniProt corroborates the exact CBL partner. The original pair-level table remains uninspected. Retain qualitative association without transferring a KRAS phenotype, direct-contact mechanism or substrate status to CBL. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain the recorded neurodegeneration-network association. Reason: The exact partner edge in PMID:32814053 is corroborated by the reviewed CBL entry. The original target-specific experiment was not independently recovered. The association is retained as non-core without making the partner a CBL substrate or assigning CBL the partnerβs neurodegenerative disease mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain the recorded neurodegeneration-network association. Reason: The exact partner edge in PMID:32814053 is corroborated by the reviewed CBL entry. The original target-specific experiment was not independently recovered. The association is retained as non-core without making the partner a CBL substrate or assigning CBL the partnerβs neurodegenerative disease mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the supported CBLβYWHAB (14-3-3 beta/alpha) interaction to 14-3-3 protein binding. Reason: The exact P31946 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original BioPlex cell-specific target table was not independently inspected; no cell-type-independent mechanism is inferred. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the exact BioPlex network association. Reason: PMID:33961781 is a systematic affinity-interaction source, and the reviewed CBL record corroborates this exact partner. Its original target table remains uninspected. Retain qualitative non-core binding; do not infer a purified interface or a partner-specific catalytic activity from a network edge. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the exact BioPlex network association. Reason: PMID:33961781 is a systematic affinity-interaction source, and the reviewed CBL record corroborates this exact partner. Its original target table remains uninspected. Retain qualitative non-core binding; do not infer a purified interface or a partner-specific catalytic activity from a network edge. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the supported CBLβYWHAG (14-3-3 gamma) interaction to 14-3-3 protein binding. Reason: The exact P61981 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original BioPlex cell-specific target table was not independently inspected; no cell-type-independent mechanism is inferred. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:33961781 supplies cell-specific BioPlex association evidence. The original CBLβGRB2 target table and contact surface remain uninspected. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Refine the supported CBLβYWHAH (14-3-3 eta) interaction to 14-3-3 protein binding. Reason: The exact Q04917 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original BioPlex cell-specific target table was not independently inspected; no cell-type-independent mechanism is inferred. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the exact BioPlex network association. Reason: PMID:33961781 is a systematic affinity-interaction source, and the reviewed CBL record corroborates this exact partner. Its original target table remains uninspected. Retain qualitative non-core binding; do not infer a purified interface or a partner-specific catalytic activity from a network edge. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Refine the supported CBLβYWHAG (14-3-3 gamma) interaction to 14-3-3 protein binding. Reason: The exact P61981 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original OpenCell pair record was not independently inspected; imaging or coassociation is not recast as a purified direct-binding assay. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Refine the supported CBLβYWHAE (14-3-3 epsilon) interaction to 14-3-3 protein binding. Reason: The exact P62258 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original OpenCell pair record was not independently inspected; imaging or coassociation is not recast as a purified direct-binding assay. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Refine the supported CBLβYWHAZ (14-3-3 zeta/delta) interaction to 14-3-3 protein binding. Reason: The exact P63104 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original OpenCell pair record was not independently inspected; imaging or coassociation is not recast as a purified direct-binding assay. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAQ (14-3-3 theta/tau) interaction to 14-3-3 protein binding. Reason: The exact P27348 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAB (14-3-3 beta/alpha) interaction to 14-3-3 protein binding. Reason: The exact P31946 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβSFN (14-3-3 sigma) interaction to 14-3-3 protein binding. Reason: The exact P31947 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAG (14-3-3 gamma) interaction to 14-3-3 protein binding. Reason: The exact P61981 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAE (14-3-3 epsilon) interaction to 14-3-3 protein binding. Reason: The exact P62258 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAZ (14-3-3 zeta/delta) interaction to 14-3-3 protein binding. Reason: The exact P63104 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Refine the supported CBLβYWHAH (14-3-3 eta) interaction to 14-3-3 protein binding. Reason: The exact Q04917 partner is a 14-3-3 family member and its CBL association is independently corroborated in the reviewed UniProt interaction record. The original systematic 14-3-3 target record was not independently inspected; no claim is made that all seven partner rows arose from one experiment. GO:0071889 specifies binding to this protein class; it does not assign phosphoserine recognition to CBL or specify the interaction surface. This is a more informative description of the retained qualitative interaction, with the original assay-access limit preserved. Proposed replacements: 14-3-3 protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the source-specific CBLβGRB2 association without assigning an unresolved interface. Reason: PMID:40205054 supplies a multimodal cell-map context. The exact CBLβGRB2 interaction record and interface remain uninspected. The exact curated UniProt edge and independent PMID:11997436 support the interaction. The latter establishes an SH3-mediated recruitment mode, already represented in the core, but does not establish that this original assay uses the same domain rather than another GRB2 contact or a larger complex. Retain generic non-core binding under the standing policy; partner identity alone is insufficient for this domain-specific replacement. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the exact Cell Map interaction-network association. Reason: PMID:40205054 is a systematic interaction source and UniProt corroborates this exact partner. The original target-specific table remains uninspected. Retain the qualitative association without asserting binary contact, a new process or substrate status. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:5668240 [Stability of diluted solutions of peracetic acid]. | UNDECIDED | Summary: The SHIP2 interaction citation remains unresolved. Reason: The canonical PMID:5668240 record is an abstract-only peracetic-acid paper and does not expose the reported CBLβINPPL1 assay. That discrepancy does not establish the intended replacement PMID, an experimental wrong-gene error or absence of a real CBLβSHIP2 interaction. Preserve the original reference and exact O15357 partner while requesting provenance resolution; do not remove the experimental annotation solely from the cached title. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:7657591 Tyrosine phosphorylation of the c-cbl proto-oncogene protein... | MODIFY | Summary: Refine EGFR association to receptor tyrosine kinase binding. Reason: PMID:7657591 directly tests CBL binding to phosphorylated EGFR using the N-terminal CBL region. This supports recognition of the RTK partner without transferring its kinase activity to CBL. Proposed replacements: receptor tyrosine kinase binding Supporting Evidence: PMID:7657591 associates with activated EGF receptor |
| GO:0005515 protein binding | IPI PMID:8524328 The product of the cbl oncogene forms stable complexes in vi... | MODIFY | Summary: Refine binding to the CRK SH2 domain. Reason: PMID:8524328 describes CRK SH2-domain association with tyrosine-phosphorylated CBL. CBL is the ligand for the partner domain, so SH2-domain binding is appropriate; phosphotyrosine-residue recognition by CBL would reverse the experimentally described direction. Proposed replacements: SH2 domain binding Supporting Evidence: PMID:8524328 this interaction is mediated by the SH2 domain of Crk |
| GO:0005515 protein binding | IPI PMID:8626543 Stimulation through the T cell receptor induces Cbl associat... | MODIFY | Summary: Refine the CRK-family interaction to SH2-domain binding. Reason: PMID:8626543 investigates CRK/CRKL association with phosphorylated CBL in human T-cell contexts and maps recognition to the partner SH2 domain. CBL supplies the phosphorylated binding sequence. This supports SH2-domain binding, not CBL reading phosphotyrosine on CRK or CRKL. Proposed replacements: SH2 domain binding Supporting Evidence: PMID:8626543 Cbl was able to interact with the Crk SH2 domain |
| GO:0005515 protein binding | IPI PMID:8626543 Stimulation through the T cell receptor induces Cbl associat... | MODIFY | Summary: Refine the CRK-family interaction to SH2-domain binding. Reason: PMID:8626543 investigates CRK/CRKL association with phosphorylated CBL in human T-cell contexts and maps recognition to the partner SH2 domain. CBL supplies the phosphorylated binding sequence. This supports SH2-domain binding, not CBL reading phosphotyrosine on CRK or CRKL. Proposed replacements: SH2 domain binding Supporting Evidence: PMID:8626543 Cbl was able to interact with the Crk SH2 domain |
| GO:0005515 protein binding | IPI PMID:8663231 Activation-modulated association of 14-3-3 proteins with Cbl... | MODIFY | Summary: Refine the 14-3-3 theta interaction. Reason: The source studies CBL association with 14-3-3 proteins and the role of CBL serine phosphorylation. The binding partner is the 14-3-3 adaptor; the informative CBL activity is binding that protein, not recognition of a phosphoserine residue. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:8663231 association between 14-3-3tau and Cbl was detected |
| GO:0005515 protein binding | IPI PMID:9092538 Serine phosphorylation of Cbl induced by phorbol ester enhan... | MODIFY | Summary: Refine the 14-3-3 theta interaction. Reason: The source studies CBL association with 14-3-3 proteins and the role of CBL serine phosphorylation. The binding partner is the 14-3-3 adaptor; the informative CBL activity is binding that protein, not recognition of a phosphoserine residue. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:9092538 interaction between Cbl and two 14-3-3 isoforms |
| GO:0005515 protein binding | IPI PMID:9160881 Yeast two-hybrid in vivo association of the Src kinase Lyn w... | MODIFY | Summary: Refine p85 recognition to PI3K regulatory-subunit binding. Reason: PMID:9160881 maps association between CBL and the p85 regulatory subunit using two-hybrid and biochemical domain/phosphorylation comparisons. The tested subunit is the regulatory partner; neither PI3K catalysis nor phosphotyrosine recognition by CBL follows from p85 recognizing CBL. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: PMID:9160881 p85 interacts with the proline-rich domain of Cbl |
| GO:0005515 protein binding | IPI PMID:9447983 A novel, multifuntional c-Cbl binding protein in insulin rec... | KEEP AS NON CORE | Summary: Retain the recorded mouse CAP association with the construct limit. Reason: The complete PMID:9447983 abstract describes CAP SH3-mediated association with CBL in the 3T3-L1 insulin-signaling context. The exact human CBL construct behind this source row was not independently resolved. Preserve the Q62417 mouse partner and retain the plausible conserved association under curator deference, rather than remove it because the paper uses a model system. The separately curated SH3-domain activity remains independently supported. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9890970 Fyn associates with Cbl and phosphorylates tyrosine 731 in C... | MODIFY | Summary: Refine p85 association to PI3K regulatory-subunit binding. Reason: PMID:9890970 tests CBL phosphorylation-site mutants and the p85 association, including loss of binding after mutation of the relevant CBL site. The measured partner is PI3K p85; CBL is not thereby assigned the partnerβs phosphotyrosine-reader or lipid-kinase activity. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: PMID:9890970 Mutation of Tyr731 in GST-CBL-LZIP eliminated binding of the p85 subunit |
| GO:0005515 protein binding | IPI PMID:9890970 Fyn associates with Cbl and phosphorylates tyrosine 731 in C... | MODIFY | Summary: Refine the FYN association to protein tyrosine kinase binding. Reason: PMID:9890970 studies FYN-dependent CBL phosphorylation and association. Preserve the exact P39688 xenolog partner and avoid assuming a human-only construct. The supported refinement is binding a protein tyrosine kinase, not transferring FYN catalysis to CBL. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:9890970 Fyn was observed to be constitutively associated with Cbl |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the cytoplasmic pool of CBL. Reason: The UniProt subcellular-location mapping agrees with soluble CBL and its regulated recruitment to receptor complexes. Cytoplasm is broader than cytosol and is compatible with peripheral membrane association; it does not imply a transmembrane segment or an exclusively cytoplasmic distribution. Supporting Evidence: GO_REF:0000120 |
| GO:0005794 Golgi apparatus | IDA PMID:29237719 IFT20 modulates ciliary PDGFRΞ± signaling by regulating the s... | KEEP AS NON CORE | Summary: Retain the assayed Golgi localization as non-core. Reason: PMID:29237719 uses GFP-tagged human CBL in murine fibroblast contexts and identifies a Golgi pool alongside the primary-cilium region. The construct and host species are kept distinct. This supports contextual localization without establishing a universal endogenous human Golgi function. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain Golgi localization with the ortholog/construct limit. Reason: The mouse-derived location is biologically consistent with the independently inspected human CBL construct in the Golgi/ciliary study. The original propagated source and access limit remain explicit; no independent endogenous human localization experiment is invented. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the directly curated cytosolic localization. Reason: The HPA IDA is consistent with the independently established soluble CBL pool and recruitment to receptor signaling complexes. The original HPA image was not re-adjudicated here; retention rests on curator deference plus coherent independent biology, not a claim that the image was inspected. Supporting Evidence: GO_REF:0000052 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1112690 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-1112690 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225949 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-1225949 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1225960 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-1225960 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295621 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-1295621 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295622 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-1295622 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182969 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-182969 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182986 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-182986 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182988 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-182988 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182990 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-182990 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182993 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-182993 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183036 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183036 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183051 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183051 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183052 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183052 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183055 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183055 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183058 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183058 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183067 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183067 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183072 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183072 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183084 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183084 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183089 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183089 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-183094 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-183094 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205244 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-205244 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332235 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-4332235 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332236 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-4332236 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5637794 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5637794 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654672 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654672 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654673 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654673 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654677 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654677 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654679 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654679 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654684 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654684 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654729 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654729 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654730 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654730 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5654734 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-5654734 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-879917 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-879917 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848818 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8848818 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848829 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8848829 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8866279 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8867754 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8867756 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868071 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868072 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868230 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868236 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868648 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868651 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868658 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868659 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868660 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8868661 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8869438 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8871193 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8871194 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8874685 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8874685 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875183 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8875183 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875451 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8875451 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875482 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8875482 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875490 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8875490 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876240 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8876240 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876258 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-8876258 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912627 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-912627 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912727 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-912727 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912734 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-912734 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-912790 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-912790 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-934604 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-934604 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706293 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-9706293 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706350 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-9706350 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706354 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-9706354 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9706356 | ACCEPT | Summary: Retain cytosolic CBL in the specified curated reaction. Reason: The source reaction places CBL in a signaling complex compatible with its soluble cytosolic pool and recruitment to the cytoplasmic side of membranes. Retain this broad compartment under curator deference. Some events phosphorylate, recruit, sequester or release CBL; this location assertion does not claim that CBL catalyses every event or that the cached summary independently reproduces the full Reactome physical-entity hierarchy. Supporting Evidence: Reactome:R-HSA-9706356 |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited plasma-membrane association. Reason: The PAINT assertion is consistent with direct target evidence for recruitment of CBL to the cytoplasmic face of activated receptor complexes. The PTN placement and alignment were not independently re-examined. CBL appearing among descendant evidence is expected and is not circular support. |
| GO:0005886 plasma membrane | IDA PMID:15465819 Ubiquitin ligase activity of c-Cbl guides the epidermal grow... | ACCEPT | Summary: Retain CBL at the membrane during receptor trafficking. Reason: The source tests CBL-dependent recruitment of endocytic machinery and entry of ligand-bound EGFR into coated pits. This is peripheral association with the cytoplasmic membrane face, not an integral-membrane topology claim. Supporting Evidence: PMID:15465819 plasma membrane recruitment of Eps15 |
| GO:0005886 plasma membrane | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | ACCEPT | Summary: Retain membrane-associated CBL in LAG3 signaling. Reason: The original study links CBL to ligand-engaged LAG3 at the plasma membrane, with human Jurkat and primary T-cell controls. CBL/CBLB single-loss versus double-loss and rescue establish redundancy in this context; they do not make CBL necessary on its own in every T cell. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the conserved membrane-associated CBL pool. Reason: The mouse-derived location agrees with independent human receptor-associated CBL evidence. CBL is recruited to the cytoplasmic face rather than spanning the bilayer; the original donor identity is preserved. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1225956 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1225960 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-182986 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-182994 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-183002 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-183036 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-183058 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-183084 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867041 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867044 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867047 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8951490 | ACCEPT | Summary: Retain plasma-membrane CBL in the specified receptor context. Reason: The complete cached Reactome summary describes the specified receptor-associated event, consistent with independent CBL recruitment at the cytoplasmic membrane face. A location assertion does not confer the receptor or kinase activity on CBL, and mutant-specific reductions in binding do not negate the broader membrane-associated pool. |
| GO:0005925 focal adhesion | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific focal-adhesion transfer remains unresolved. Reason: The rat/Ensembl source is preserved, but the original donor localization assay and its target-specific controls were not independently recovered. Interaction with focal-adhesion signaling proteins alone does not establish occupancy of the focal-adhesion structure. This is an evidence-access limit, not a claim that the location is impossible. Supporting Evidence: GO_REF:0000107 |
| GO:0005929 cilium | IDA PMID:29237719 IFT20 modulates ciliary PDGFRΞ± signaling by regulating the s... | KEEP AS NON CORE | Summary: Retain contextual ciliary localization. Reason: PMID:29237719 distinguishes GFP-tagged human CBL localization in murine cells from endogenous mouse Cbl enrichment after PDGF-AA stimulation. The inspected ciliary-marker and Golgi comparisons support this contextual localization. It is not a claim that CBL is a constitutive IFT-B subunit or that every human cell uses this compartment. Supporting Evidence: |
| GO:0005929 cilium | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the mouse-derived ciliary localization with its model limit. Reason: The source is consistent with the ciliary PDGFRA study, including human CBL constructs in murine cells. Preserve the mouse transfer and avoid recasting it as a direct endogenous human imaging experiment. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Retain ubiquitin-dependent protein catabolism. Reason: CBL performs the substrate-ubiquitination step that can commit activated receptors to degradation. Independent human CBL variant and receptor-degradation evidence supports the process; CBL is neither the protease nor a passive substrate in this assertion. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:25178484 RASopathy-associated CBL germline mutations cause aberrant u... | ACCEPT | Summary: Retain CBL participation in receptor degradation. Reason: The source compares human CBL disease variants with wild-type CBL and reports impaired EGFR ubiquitination and degradation for selected variants. Together with direct E3 evidence, this identifies the step performed by CBL rather than inferring participation solely from disease or necessity. Supporting Evidence: PMID:25178484 impaired CBL-mediated EGFR ubiquitylation and degradation |
| GO:0006513 protein monoubiquitination | IEA GO_REF:0000107 | ACCEPT | Summary: Retain monoubiquitination as a CBL reaction. Reason: The rat transfer is independently consistent with curated CBL monoubiquitination reactions for CIN85 and MET. This does not assert that every substrate receives only one ubiquitin, nor erase the independently supported polyubiquitination activity. Supporting Evidence: GO_REF:0000107 Reactome:R-HSA-182986 Reactome:R-HSA-8875183 |
| GO:0006974 DNA damage response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain a contextual DNA-damage response with the mechanistic controls distinguished from abundance changes. Reason: PMID:19546888 tests camptothecin-treated rat neuronal cells, including combined Cbl/Cbl-b knockdown that sensitizes PC12 cells to death. Human-cell knockdown and human c-Cbl construct experiments place a suppressive action at MLK-to-MKK/JNK signaling, although the precise noncatalytic interaction mechanism remains unresolved. The DNA-damage experiment is not merely a measurement of Cbl disappearance, but the double-knockdown result does not isolate CBL from CBLB. Retain the broad transferred response as non-core with these model and redundancy limits, without assigning CBL a DNA-repair enzyme activity. Supporting Evidence: GO_REF:0000107 PMID:19546888 sensitized neuronal cells to death promoted by NGF deprivation or DNA damage |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain broad signal transduction as non-core. Reason: The inherited assertion is consistent with CBL catalytic and recruitment roles, but the broad process does not describe its specific work as precisely as the E3 and receptor-regulation assertions. The PAINT node placement was not independently inspected; donor number is not used to discount the inheritance judgment. Supporting Evidence: GO_REF:0000033 |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain broad cell-surface receptor signaling as non-core. Reason: The InterPro mapping is coherent with CBL recruitment and regulation of receptor complexes. Retention does not equate an intracellular E3/adaptor with a membrane receptor or imply that all CBL substrates generate the same signaling outcome. Supporting Evidence: GO_REF:0000002 |
| GO:0008584 male gonad development | IEA GO_REF:0000107 | UNDECIDED | Summary: Male gonad development remains a narrower unresolved claim than the established testicular phenotype. Reason: The prior claim that Cbl-null mice are fertile and lack a gonadal phenotype is contradicted by PMID:16301331: the paper reports disrupted seminiferous germ-cell organization, loss of postmeiotic cells and predominantly male hypofertility. However, GO:0008584 concerns progression of the male gonad to its mature structure. The inspected experiments principally resolve adult germ-cell homeostasis and androgen-dependent apoptosis; an earlier developmental apoptotic defect is proposed in the Discussion as ongoing work. The precise developmental step behind this rat-to-human assertion remains unresolved. Preserve the source and positive testicular evidence without equating adult hypofertility with a demonstrated human gonad-development mechanism. |
| GO:0010332 response to gamma radiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The traced irradiation readout overextends the demonstrated role of CBL. Reason: The dated official comparative graph links the rat gamma-radiation IEP annotation to PMID:16301331. In that source, localized irradiation removes successive germ-cell populations so that changing Cbl abundance can identify the cells that normally express it. The authors explicitly consider loss of spermatocytes and altered expression as explanations. These experiments do not resolve a CBL activity executing the gamma-radiation response; CBL is measured as a marker in a cell-depletion experiment. Transferring this readout as the human process assertion overstates the demonstrated role. This conclusion follows the actual assay, not the IEP code alone, and does not imply that CBL cannot modulate other DNA-damage or apoptotic responses. Supporting Evidence: GO_REF:0000107 PMID:16301331 To assess the testicular cell population supporting Cbl transcript and protein expression |
| GO:0014823 response to activity | IEA GO_REF:0000107 | UNDECIDED | Summary: The activity-response transfer needs its donor experiment. Reason: The exact rat/Ensembl source remains unchanged. The donor intervention, CBL-specific assay and meaning of activity in that experiment were not independently resolved. An electronic or expression-pattern evidence code alone is not a basis for dismissing the process. Supporting Evidence: GO_REF:0000107 |
| GO:0016567 protein ubiquitination | IDA PMID:17974561 Tesk1 interacts with Spry2 to abrogate its inhibition of ERK... | ACCEPT | Summary: Retain CBL-dependent protein ubiquitination. Reason: PMID:17974561 distinguishes Tesk1 effects on SPRY2 signaling from its lack of effect on SPRY2 inhibition of CBL-mediated EGFR ubiquitination. That contextual negative result does not negate the positively established CBL ubiquitination reaction. Supporting Evidence: PMID:17974561 Cbl-mediated ubiquitination of the epidermal growth factor receptor |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the mapped protein-ubiquitination process. Reason: The mouse/UniPathway mapping agrees with direct human CBL E3 activity and substrate ubiquitination. The target itself performs the ubiquitination step; no new biological process is inferred merely from a binding interaction. |
| GO:0016567 protein ubiquitination | IMP PMID:17094949 Spred-2 steady-state levels are regulated by phosphorylation... | ACCEPT | Summary: Retain the SPRED ubiquitination context. Reason: The study combines CBL/CBLB depletion, dominant inhibitory CBL and wild-type CBL overexpression with SPRED ubiquitination measurements. These support CBL participation, while preserving paralog redundancy and distinguishing ubiquitination from a claim that CBL is a kinase. Supporting Evidence: PMID:17094949 wild type Cbl enhanced Spred-2 ubiquitination |
| GO:0016567 protein ubiquitination | TAS PMID:15465819 Ubiquitin ligase activity of c-Cbl guides the epidermal grow... | ACCEPT | Summary: Retain ubiquitination in EGFR trafficking. Reason: The source connects CBL ligase activity to endocytic recruitment and receptor uptake. Independent E3 assays identify CBL as performing the ubiquitination step, rather than merely associating with a ubiquitinated protein. |
| GO:0016600 flotillin complex | IEA GO_REF:0000107 | UNDECIDED | Summary: Flotillin-complex membership remains unresolved. Reason: The exact mouse source is preserved. CAP-associated recruitment to a flotillin-containing membrane domain is not by itself proof of membership in the specifically named complex. The donor complex-isolation or membership evidence was not independently recovered, so the prior confident membership claim is not retained without that evidence. Supporting Evidence: GO_REF:0000107 |
| GO:0016600 flotillin complex | ISS GO_REF:0000024 | UNDECIDED | Summary: Flotillin-complex membership remains unresolved. Reason: The exact mouse source is preserved. CAP-associated recruitment to a flotillin-containing membrane domain is not by itself proof of membership in the specifically named complex. The donor complex-isolation or membership evidence was not independently recovered, so the prior confident membership claim is not retained without that evidence. Supporting Evidence: GO_REF:0000024 |
| GO:0017124 SH3 domain binding | IEA GO_REF:0000120 | ACCEPT | Summary: Retain SH3-domain binding as an own recruitment activity. Reason: CBL proline-rich sequences bind SH3 domains of partners such as CIN85 and intersectin. The contacted domain belongs to the partner, so the direction is appropriate. Direct target evidence supports the activity independently of the uninspected individual ARBA rule logic. |
| GO:0017124 SH3 domain binding | IPI PMID:9447983 A novel, multifuntional c-Cbl binding protein in insulin rec... | ACCEPT | Summary: Retain the experimentally curated SH3-domain activity. Reason: The source describes SH3-mediated CAPβCBL association in a mouse 3T3-L1 context. Preserve the exact mouse CAP partner and defer to the curator for the original CBL construct mapping. Independent CBLβCIN85 structures establish the same own molecular activity; this is not a claim that the original experiment was wholly human. |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-9607240 | KEEP AS NON CORE | Summary: Retain cytokine-pathway participation in its specific context. Reason: The complete Reactome FLT3 pathway summary supplies a cytokine-signaling context for CBL-mediated receptor regulation. This is contextual pathway participation rather than a separate cytokine-binding or receptor activity of CBL. Supporting Evidence: Reactome:R-HSA-9607240 |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain broad protein-kinase binding as non-core. Reason: Independent target experiments establish CBL association with receptor and non-receptor tyrosine kinases. The broad rat-derived assertion is sound, while more informative existing partner-class annotations provide its mechanistic coverage. |
| GO:0023051 regulation of signaling | IEA GO_REF:0000002 | ACCEPT | Summary: Retain regulation of signaling. Reason: The domain mapping agrees with experimentally established CBL ubiquitination and recruitment mechanisms that alter receptor-signal duration. Retention does not imply that CBL is always a negative regulator in every pathway. |
| GO:0030424 axon | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific neuronal location requires donor-level verification. Reason: The rat/Ensembl source is retained exactly. Its target-localization experiment, neuronal compartment markers and human transfer were not independently resolved. General neuronal expression or receptor association would not by itself establish this specific compartment, but absent access is not evidence against the annotation. Supporting Evidence: GO_REF:0000107 |
| GO:0030426 growth cone | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific neuronal location requires donor-level verification. Reason: The rat/Ensembl source is retained exactly. Its target-localization experiment, neuronal compartment markers and human transfer were not independently resolved. General neuronal expression or receptor association would not by itself establish this specific compartment, but absent access is not evidence against the annotation. Supporting Evidence: GO_REF:0000107 |
| GO:0030971 receptor tyrosine kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited receptor-tyrosine-kinase binding. Reason: Direct CBL receptor-recognition studies support the molecular activity independently of the PAINT donor list. The exact ancestral node and alignment were not inspected, so no unsupported assertion about the evolutionary depth of acquisition is made. Indirect GRB2-assisted recruitment is distinguished from direct TKB binding, and a fly donor does not weaken the inherited claim merely by being the only listed experimental member. |
| GO:0033574 response to testosterone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the contextual androgen response with the rodent cellular mechanism bounded. Reason: PMID:16301331 combines rat flutamide, hypophysectomy/testosterone replacement and Sertoli-cell/germ-cell cocultures with Cbl-null mouse tests. Hormonal manipulation changes Cbl expression, but the knockout experiments additionally alter androgen-dependent germ-cell apoptosis and downstream protein balance. Thus a functional Cbl contribution is supported beyond expression alone. The germ-cell response is mediated through its cellular environment rather than demonstrated direct androgen-receptor binding by CBL; no direct Bim or Smac ubiquitination was detected in these testicular assays. Retain the broad response as non-core, with rodent physiology and untested human gonadal context explicit. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the PDGF-response context as non-core. Reason: Independent target evidence connects CBL receptor binding and E3 activity to PDGF receptor ubiquitination and signaling feedback. This supports qualitative response participation without claiming that the original rat donor assay was inspected or that CBL alone is universally necessary. |
| GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain PI3K regulatory-subunit binding as non-core. Reason: Independent biochemical studies support the CBLβp85 association. In that interaction p85 can recognize phosphorylated CBL; the assertion is binding a PI3K regulatory subunit, not CBL possessing PI3K or phosphotyrosine-reader activity in this edge. |
| GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited negative regulation of EGFR signaling. Reason: Direct human CBL E3 and disease-variant evidence supports the conserved receptor-downregulation function. The PAINT placement was not independently reconstructed; human CBL among descendant evidence is expected rather than circular. |
| GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the electronic EGFR-downregulation assertion. Reason: Direct target ubiquitination, degradation and signaling measurements support this function independently of the uninspected ARBA rule logic and mouse transfer details. |
| GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway | IMP PMID:25178484 RASopathy-associated CBL germline mutations cause aberrant u... | ACCEPT | Summary: Retain the experimentally supported EGFR feedback function. Reason: The study directly compares CBL variants with wild type for EGFR ubiquitination/degradation, receptor uptake and downstream signaling. CBL supplies the E3 step responsible for attenuation; the interpretation is not based only on the clinical phenotype. Supporting Evidence: PMID:25178484 enhanced ERK phosphorylation in cells expressing mutant CBL |
| GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway | TAS Reactome:R-HSA-182971 | ACCEPT | Summary: Retain the curated EGFR-downregulation pathway. Reason: The complete Reactome summary explicitly assigns CBL receptor ubiquitination and recruitment functions in EGFR downregulation. This does not make CBL the membrane-bending protein or the lysosomal protease. Supporting Evidence: Reactome:R-HSA-182971 |
| GO:0042594 response to starvation | IEA GO_REF:0000107 | UNDECIDED | Summary: The starvation-response donor evidence remains unresolved. Reason: The exact rat/Ensembl source is preserved, but the target-specific starvation experiment was not independently recovered. It is inappropriate to infer expression-only evidence or lack of participation from the transfer code alone. Supporting Evidence: GO_REF:0000107 |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain context-dependent suppression of apoptosis. Reason: PMID:19546888 provides positive c-Cbl protection against MLK-driven death in rat PC12 cells, including a RING-defective construct, and human-cell evidence that c-Cbl suppresses signaling between MLKs and MKK4/7. Cbl-b does not reproduce every c-Cbl overexpression result, and double knockdown contributes to the broader neuronal sensitization experiments. The precise protective interaction mechanism is unresolved and is not assumed to be E3-mediated destruction of MLK3. Opposite pro-apoptotic effects in osteoblast or testicular contexts do not negate this source-specific protective role. Keep it non-core rather than universalizing survival regulation. Supporting Evidence: GO_REF:0000107 PMID:19546888 expression of c-Cbl blocks the ability of MLKs to signal |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:18070883 A novel role of Sprouty 2 in regulating cellular apoptosis. | MARK AS OVER ANNOTATED | Summary: The source does not establish an anti-apoptotic action of CBL itself. Reason: Selected original PMID:18070883 Results and controls in human SW13 cells show SPRY2 supporting serum-dependent survival by restraining CBL-mediated receptor downregulation; dominant inhibitory CBL-TKB preserves survival after SPRY2 depletion. That is a source-specific scope/direction problem for assigning the anti-apoptotic action to active CBL. It does not establish that CBL can never support survival in other contexts. The canonical cache contains abstract/Discussion, while the inspected Results were accessed externally; no complete-paper or supplement claim is made. Supporting Evidence: PMID:18070883 hSPRY2 to sequester c-Cbl and thereby augment signaling via growth factor receptors |
| GO:0043303 mast cell degranulation | IEA GO_REF:0000107 | UNDECIDED | Summary: The mast-cell degranulation transfer needs its source assay. Reason: The exact rat/Ensembl source is preserved. Neither CBL family reputation as a signaling inhibitor nor lack of a direct granule-fusion activity settles this existing process assertion. The donor perturbation and CBL-specific role were not independently recovered, so retain uncertainty rather than a blanket over-annotation decision. Supporting Evidence: GO_REF:0000107 |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited membrane-raft localization. Reason: The PAINT assertion is positively supported by human osteoblast evidence placing CBL with FGFR2 in membrane-raft microdomains. The specific PTN placement was not inspected, and this is not a claim that all CBL is raft-associated. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | UNDECIDED | Summary: The CBL-specific cadherin interaction remains unresolved. Reason: The source is an E-cadherin proximity/interactome study, but its exact CBL target entry and validation were not independently inspected. Proximity does not automatically establish a purified binary interaction; equally, a known CBLL1/Hakai mechanism does not prove this CBL assertion is a paralog error. Preserve the experimental record and uncertainty. Supporting Evidence: |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | UNDECIDED | Summary: The ethanol-response transfer needs donor-level assessment. Reason: The original rat/Ensembl source is retained. The actual CBL intervention, response and transfer boundary were not recovered, so the earlier categorical expression-only dismissal is unsupported. This is an access-limited judgment, not a positive mechanistic claim. Supporting Evidence: GO_REF:0000107 |
| GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway | TAS Reactome:R-HSA-8849469 | KEEP AS NON CORE | Summary: Retain context-dependent positive EGFR regulation through the curated CBL autoubiquitination step as non-core. Reason: The complete human Reactome pathway and its specific reactions distinguish PTK6-mediated phosphorylation of CBL (R-HSA-8848818) from CBL autoubiquitination (R-HSA-8848829), which promotes CBL degradation and attenuates receptor downregulation. CBL performs the ubiquitin-transfer step itself in the latter event, rather than serving only as an inhibited substrate. This supports the existing TAS process as a context-dependent, non-core role without reversing its usual negative receptor-regulatory function. The underlying primary full text was not inspected; this decision defers to the explicit curated human reaction, not to a pathway-title inference. Supporting Evidence: Reactome:R-HSA-8849469 Reactome:R-HSA-8848818 Reactome:R-HSA-8848829 |
| GO:0046718 symbiont entry into host cell | TAS Reactome:R-HSA-8875360 | KEEP AS NON CORE | Summary: Retain the host-pathogen entry context as non-core. Reason: The complete Reactome summary connects CBL-mediated MET ubiquitination and endocytosis to InlB-dependent Listeria entry. CBL performs a receptor-trafficking step used by the pathogen; this is a contextual role, not a distinct pathogen-recognition activity. Supporting Evidence: Reactome:R-HSA-8875360 |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain structural metal binding as non-core. Reason: The RING zinc-binding architecture supports the electronic annotation. Bound structural metal is part of E3 architecture, not an independent metal-homeostasis or transport function. Supporting Evidence: GO_REF:0000002 |
| GO:0046875 ephrin receptor binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain ephrin-receptor binding as a specific non-core context. Reason: The EphB1 study maps CBL recruitment through its TKB region and compares wild-type with ligase-impaired CBL for receptor ubiquitination/degradation. The specific receptor interaction is sound but is one instance of the broader core RTK-recognition function; no ephrin ligand or receptor activity is assigned to CBL. |
| GO:0046875 ephrin receptor binding | IPI PMID:18034775 Ligand binding induces Cbl-dependent EphB1 receptor degradat... | KEEP AS NON CORE | Summary: Retain ephrin-receptor binding as a specific non-core context. Reason: The EphB1 study maps CBL recruitment through its TKB region and compares wild-type with ligase-impaired CBL for receptor ubiquitination/degradation. The specific receptor interaction is sound but is one instance of the broader core RTK-recognition function; no ephrin ligand or receptor activity is assigned to CBL. Supporting Evidence: |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IMP PMID:15465819 Ubiquitin ligase activity of c-Cbl guides the epidermal grow... | ACCEPT | Summary: Retain positive regulation of receptor-mediated endocytosis. Reason: The source tests the requirement for CBL ligase activity in Eps15 recruitment and EGFR entry into coated pits. With direct E3 evidence, this identifies CBLβs own ubiquitination contribution rather than confusing CBL with the internalized receptor or the membrane-bending machinery. Supporting Evidence: PMID:15465819 c-Cbl can guide ligand-bound EGFR into the Eps15 internalization route |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IMP PMID:25178484 RASopathy-associated CBL germline mutations cause aberrant u... | ACCEPT | Summary: Retain the receptor-internalization regulatory function. Reason: Selected human CBL variants reduce receptor-mediated EGF uptake alongside EGFR ubiquitination/degradation defects. The mechanistic E3 step supports participation; the conclusion does not rely solely on a loss-of-function phenotype. Supporting Evidence: PMID:25178484 ineffective EGFR internalization |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the contextual perinuclear CBL pool. Reason: The rat-derived location is consistent with independently inspected human CBL constructs in Golgi/perinuclear regions of murine cells. Preserve those model and construct limits; this does not independently verify the original rat donor image or establish a distinct endogenous human perinuclear function. |
| GO:0050821 protein stabilization | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | UNDECIDED | Summary: The stabilization termβs fit to LAG3-tail conformational control remains unsettled. Reason: Selected original PMID:40101708 Results compare wild-type and ubiquitination-defective LAG3 and report similar protein levels and cycloheximide half-lives, while ubiquitination stabilizes a membrane-dissociated signaling conformation. GO:0050821 includes maintenance of structure/integrity and prevention of degradation or aggregation; the negative turnover result alone does not settle that broader wording. Existing GO-CAM models 685de18700005171 and 685de18700005545 explicitly place the CBL K63 reaction within stabilization, a considered interpretation requiring engagement. Retain uncertainty about that structural-integrity correspondence rather than asserting catalytic inactivity, a model error or an absence of supporting experiments. The inspected body was external; the canonical cache remains abstract-only. Supporting Evidence: |
| GO:0050821 protein stabilization | IEA GO_REF:0000117 | UNDECIDED | Summary: The electronic stabilization assertion remains unresolved. Reason: The individual ARBA rule logic and original evidence provenance were not inspected, so this row is not assumed to derive from the LAG3 study. The target-specific stabilization boundary remains unsettled despite CBLβs demonstrated degradative and nondegradative ubiquitination roles. Preserve the source without claiming that a general E3 function excludes stabilization. Supporting Evidence: GO_REF:0000117 |
| GO:0050860 negative regulation of T cell receptor signaling pathway | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | ACCEPT | Summary: Retain CBL-mediated negative regulation of TCR signaling. Reason: The source combines human T-cell CBL/CBLB double-loss, individual rescue and LAG3 ubiquitination-site comparisons. CBL supplies a catalytic step enabling LAG3 inhibitory signaling. Redundancy with CBLB and LAG3 accounting for only part of total CBL-family suppression are retained; CBL is not itself the inhibitory receptor. Supporting Evidence: PMID:40101708 LAG3 ubiquitination, mediated redundantly by the E3 ligases c-Cbl and Cbl-b |
| GO:0050860 negative regulation of T cell receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the electronic TCR-regulatory function. Reason: Direct human CBL-dependent LAG3 ubiquitination and rescue evidence supports this target function independently of the uninspected ARBA rule logic. It is not inferred merely from another CBL-family member or from interaction with a TCR component. |
| GO:0050868 negative regulation of T cell activation | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | KEEP AS NON CORE | Summary: Retain negative regulation of T-cell activation as non-core. Reason: The human LAG3 study supports a T-cell activation outcome from CBL-family ubiquitination, with knockout/rescue and cytokine-response controls. This broader cellular outcome is kept distinct from the E3 and receptor-signaling mechanism and does not imply that CBL alone is indispensable. Supporting Evidence: |
| GO:0050868 negative regulation of T cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain negative regulation of T-cell activation as non-core. Reason: The human LAG3 study supports a T-cell activation outcome from CBL-family ubiquitination, with knockout/rescue and cytokine-response controls. This broader cellular outcome is kept distinct from the E3 and receptor-signaling mechanism and does not imply that CBL alone is indispensable. |
| GO:0051865 protein autoubiquitination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain CBL autoubiquitination as a regulatory side reaction. Reason: The original rat transfer is consistent with direct CBL autoubiquitination measurements in the structural/activation study and curated receptor-signaling reactions. This is supported target chemistry, not an inference that every RING E3 necessarily ubiquitinates itself. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:17003487 Down-regulation of ubiquitin ligase Cbl induced by twist hap... | MODIFY | Summary: Refine the PI3K/Akt regulatory direction for the source experiment. Reason: The human SaethreβChotzen osteoblast study reports reduced CBL-mediated PI3K degradation and increased PI3K/Akt signaling; CBL re-expression reverses the increased signaling. Selected original Results and controls support negative regulation by CBL in this setting. This does not deny that CBL can also recruit PI3K in other signaling complexes. Proposed replacements: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction Supporting Evidence: PMID:17003487 Transfection with Twist or Cbl abolished the increased PI3K/Akt signaling |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:10514377 The tyrosine kinase negative regulator c-Cbl as a RING-type,... | ACCEPT | Summary: Retain directly demonstrated RING E3 activity. Reason: The source demonstrates CBL recognition of tyrosine-phosphorylated substrates and recruitment/allosteric activation of an E2 through the RING region. This establishes CBL E3 activity rather than a transferred kinase activity. Supporting Evidence: |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:14661060 Cbl-c suppresses v-Src-induced transformation through ubiqui... | ACCEPT | Summary: Retain the curated E3 activity with the source correction limit. Reason: The source includes Cbl-family comparisons despite foregrounding Cbl-c. The later correction replaces Figures 2 and 3; the notice was read but corrected image pixels were not inspected. Independently demonstrated CBL E3 activity supports retention under curator deference without asserting that the exact original CBL panel was revalidated. |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:17509076 The localization of FGFR3 mutations causing thanatophoric dy... | ACCEPT | Summary: Retain E3 activity without generalizing the FGFR3 negative controls. Reason: Selected original Results show that the tested FGFR3 contexts did not behave as straightforward CBL substrates; this does not refute the independently established catalytic activity of CBL. The identified corrigendum concerns authorship. Retain the experimentally curated MF with explicit substrate-context limits rather than infer a wrong-gene citation. |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited Cbl-family E3 activity. Reason: Direct human CBL biochemical evidence supports the activity. The PAINT node/MSA were not independently inspected, but the targetβs presence among descendant evidence is legitimate and the donor count is not a weakness. No target-specific catalytic loss is established. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | ACCEPT | Summary: Retain CBL E3 activity toward LAG3. Reason: The source combines cell-based CBL-family knockout/rescue with an in-vitro reaction using cell-derived LAG3 and added purified ubiquitination components. This supports CBL E3 work while distinguishing a cell-derived substrate from an entirely purified binary system. The canonical record is abstract-only; selected Methods/Results and captions were inspected externally. |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the integrated electronic E3 assertion. Reason: The EC/domain/ortholog evidence agrees with direct CBL RING E3 assays. The individual ARBA rule logic and every source-specific donor experiment were not reconstructed, but the own target activity is independently established. |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-183036 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-183036 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-8848829 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-8848829 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-8875183 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-8875183 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-8876258 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-8876258 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-934604 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-934604 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-9706354 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-9706354 |
| GO:0061630 ubiquitin protein ligase activity | TAS Reactome:R-HSA-9706356 | ACCEPT | Summary: Retain CBL E3 activity in the specified curated reaction. Reason: The complete cached Reactome summary assigns CBL ubiquitination in the named reaction. This supports its established E3 chemistry while preserving the particular substrate and signaling context; CBL is not assigned the receptorβs kinase activity. Supporting Evidence: Reactome:R-HSA-9706356 |
| GO:0070086 ubiquitin-dependent endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain ubiquitin-dependent endocytosis. Reason: Direct target evidence connects CBL E3 activity to receptor uptake and endocytic sorting, supporting the mouse-derived process. CBL performs ubiquitination/recruitment work rather than merely being cargo; it is not claimed to bend or sever the membrane itself. |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:40101708 Ligand-induced ubiquitination unleashes LAG3 immune checkpoi... | ACCEPT | Summary: Retain K63-linked ubiquitination in the LAG3 context. Reason: Selected primary Results include linkage-specific ubiquitin reagents and ubiquitin-mutant comparisons supporting K63 chains; non-K48 wording in the abstract alone would not specify K63. CBL/CBLB redundancy and the cell-derived-substrate reconstitution limit are preserved. Other detected linkages are not treated as equally established. Supporting Evidence: PMID:40101708 non-K48-linked polyubiquitination |
| GO:0070534 protein K63-linked ubiquitination | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the electronic K63-linked ubiquitination activity. Reason: The original human LAG3 study independently supports K63-linked chain formation by the CBL-family mechanism. Retain that target basis without pretending that the individual ARBA rule or an additional EGFR chain-topology experiment was inspected. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | UNDECIDED | Summary: The hypoxia-response transfer remains source-limited. Reason: The exact rat/Ensembl source is preserved. The underlying intervention and CBL-specific functional response were not independently resolved; an oxygen/glucose-deprivation lead is not automatically equivalent to an isolated hypoxia experiment. No expression-only or biological-absence inference is made. Supporting Evidence: GO_REF:0000107 |
| GO:1990090 cellular response to nerve growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain CBL participation in a contextual NGF response. Reason: PMID:19546888 includes NGF withdrawal/readdition conditions, Cbl phosphorylation and loss, knockdown sensitization and c-Cbl-dependent suppression of MLK death signaling; its human constructs and human biochemical cell context are distinguished from rat neuronal survival assays. Independent PMID:21570973 supports CBL regulation of ligand-activated TrkA in its own model. These studies need not imply identical receptor downregulation in every neuronal context, and the 2009 study specifically treats the survival brake as distinct from assuming universal TrkA degradation. Retain the broad response as non-core without assigning NGF binding to CBL. |
| GO:1990782 protein tyrosine kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain protein-tyrosine-kinase binding. Reason: Direct CBL recognition and association studies support receptor and non-receptor tyrosine-kinase partners. The exact rat transfer is preserved; this MF neither confers kinase catalysis on CBL nor implies identical binding mechanisms for every kinase. |
| GO:2000583 regulation of platelet-derived growth factor receptor-alpha signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Retain regulation of PDGFRA signaling. Reason: The inspected IFT20 study combines human CBL constructs and association assays with murine ciliary feedback experiments; CBL and CBLB can act redundantly. Independent human mesenchymal-cell receptor-ubiquitination evidence supports transfer of the qualitative regulatory function. No claim is made that endogenous human PDGFRA regulation invariably requires cilia or CBL alone. |
| GO:2000583 regulation of platelet-derived growth factor receptor-alpha signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Retain regulation of PDGFRA signaling. Reason: The inspected IFT20 study combines human CBL constructs and association assays with murine ciliary feedback experiments; CBL and CBLB can act redundantly. Independent human mesenchymal-cell receptor-ubiquitination evidence supports transfer of the qualitative regulatory function. No claim is made that endogenous human PDGFRA regulation invariably requires cilia or CBL alone. |
| GO:0040037 negative regulation of fibroblast growth factor receptor signaling pathway | IDA PMID:11997436 FRS2 alpha attenuates FGF receptor signaling by Grb2-mediate... | NEW | Summary: Retain the genuine historical FGFR-downregulation proposal with a revised evidence basis. Reason: This record was already authored as NEW in the immutable prior main review; it is not a new assertion added in this revision. CBL performs the attenuating E3 step in the FRS2βGRB2 receptor complex, supported by the original recruitment/ubiquitination work and human FGFR2 evidence. The termβs parents describe negative signaling regulation, consistent with that work. The old comparison to SPRY/SULF proteins did not establish the same E3 role and is not retained as a gap argument; current same-role annotation coverage remains unresolved. Existing target GO-CAM models concern LAG3, not FGFR. Preserve the historical proposal and raise its comparator/coverage question without manufacturing another process assertion. |
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Download this section (compressed HTML)Q: What original reference and assay underlie the CBLβINPPL1 binding row carrying PMID:5668240? The cached record is a peracetic-acid paper; no replacement identifier has been verified.
Q: Does the FLT1 binding annotation in PMID:18273061 refer to the engineered phosphopeptide or another assay, given the reported absence of wild-type peptide binding in that experiment?
Q: How should GO:0050821 protein stabilization apply to CBL-dependent LAG3 tail conformation? The primary study finds no increased LAG3 half-life, but the definition also refers to structural integrity and existing LAG3 GO-CAMs explicitly model stabilization; that correspondence remains unresolved.
Q: What direct human source evidence resolves the rat-derived gonad-development, hypoxia, starvation and other contextual response assertions, separating an executed CBL role from cell-composition changes or expression alone?
Q: Which assay supports CBL membership in the flotillin complex rather than transient association, and what evidence identifies CBL itself in the E-cadherin proteomics row?
Q: What same-role E3 comparator coverage best evaluates the genuine historical GO:0040037 FGFR-downregulation proposal? Existing target GO-CAMs represent LAG3 rather than FGFR; no new process assertion is added here.
Q: Which molecular interaction explains RING-independent CBL suppression of MLK-to-MKK signaling, and how does this protective context coexist with pro-apoptotic CBL effects in other cells?
Q: Which GRB2 domains or indirect complexes account for the CBL interactions in the unresolved original screening contexts, especially the phosphorylation-dependent network? Demonstrated SH3-mediated recruitment is not assumed to explain every GRB2 association.
Experiment: In CBL-knockout (and CBL/CBLB double-knockout) human fibroblasts, re-express wild-type, RING-dead (C381A) or TKB-dead (G306E) CBL; measure FGF2-induced FGFR1/FRS2alpha ubiquitination, FGFR1 internalisation and degradation, and pERK kinetics.
Hypothesis: CBL ubiquitinates FGFR1 and FRS2alpha in human cells and this ubiquitination limits FGF-induced ERK duration.
Type: Genetic knockout and rescue with domain mutants
Experiment: Compare FGFR ubiquitination in cells expressing FRS2alpha with GRB2-binding tyrosines mutated versus FGFR with candidate TKB-binding sites mutated.
Hypothesis: GRB2-mediated recruitment through FRS2alpha, not direct TKB binding, is the dominant route for CBL to FGFRs.
Type: Site-directed mutagenesis and ubiquitination assays
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