CARD11 (CARMA1) is an intracellular signaling adaptor that couples antigen-receptor stimulation in lymphocytes to canonical NF-kappaB activation. Its CARD and coiled-coil region organize BCL10 assembly, while regulated recruitment of MALT1 and ubiquitin-signaling proteins builds the CBM signalosome at membrane-associated signaling sites. Phosphorylation and intramolecular interactions control access to this assembly platform. CARD11 also supports activation-associated metabolic signaling in T cells. Activating germline variants cause B-cell expansion with NF-kappaB activation and T-cell anergy (BENTA), biallelic loss of function causes combined immunodeficiency, and some heterozygous hypomorphic variants interfere with the normal protein and cause immunodeficiency with severe atopy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001772 immunological synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CARD11 is recruited to antigen-presenting-cell contact sites during T-cell signaling. Reason: The original mouse ortholog transfer is retained. Independent primary imaging of tagged CARMA1 in Jurkat-derived JPM50.6 cells conjugated to SEE-presenting Raji cells directly supports recruitment to the immune synapse. Wild-type CARMA1 accumulates at the contact, whereas the L808P construct is defective; CARMA1-deficient cells still form the contact. The exact mouse donor experiment has not been reconstructed. Main-text human cDNA sequence comparisons and cellular assays are available, but original images and the missing cached figure captions were not independently inspected. Supporting Evidence: PMID:14673152 recruitment of wild-type CARMA1 to the site of contact between Raji and JPM50.6 cells |
| GO:0002376 immune system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CARD11 participates in lymphocyte immune signaling. Reason: This broad automated process is consistent with direct assembly of the antigen-receptor signaling platform and with human lymphocyte signaling defects. It is retained as a broad context; the more informative existing adaptor and NF-kappaB terms define the core. |
| GO:0004385 GMP kinase activity | NAS PMID:11278692 CARD11 and CARD14 are novel caspase recruitment domain (CARD... | MARK AS OVER ANNOTATED | Summary: The GMP kinase assertion exceeds the catalytic evidence in the cited target study. Reason: GO:0004385 requires ATP-dependent conversion of GMP to GDP. The externally recovered original PMID:11278692 Experimental Procedures, Results and Discussion describe CARD11 domain homology, BCL10 interaction, localization and NF-kappaB reporter experiments. They characterize the PDZ-SH3-GUK region as a protein-interaction scaffold and do not report nucleotide turnover. CARD-dependent BCL10 protein phosphorylation is discussed as requiring participation of a serine/threonine kinase; it is not GMP phosphorylation by CARD11. Mark the catalytic specificity as over-annotated relative to this inspected evidence. This judgment does not infer inactivity from NAS, another MAGUK, or unexamined residues, and does not establish that CARD11 is incapable of catalysis. The canonical cache remains abstract-only; external scientific text, not original figure pixels, was read. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The source explicitly identifies CARD-mediated CARMA1βBCL10 interaction and receptor-induced physical association. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:16809782 Ca2+/calmodulin-dependent protein kinase II is a modulator o... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The source uses human CARMA1 and mouse BCL10 in some transfections and separately demonstrates endogenous Jurkat BCL10 association; these construct origins are kept distinct. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:17287217 Caveolin-1 triggers T-cell activation via CD26 in associatio... | KEEP AS NON CORE | Summary: CARD11 associates with the cytoplasmic tail of CD26. Reason: The complete source abstract explicitly reports CD26-tail interaction with CARMA1 and signaling-complex recruitment. Retain the supported association under the standing project binding policy. A tail-associated scaffold is not thereby shown to regulate CD26 peptidase catalysis, and the evidence does not make CARD11 the extracellular caveolin ligand. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17948050 Malt1 ubiquitination triggers NF-kappaB signaling upon T-cel... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The authenticated fuller source Results show stimulation-dependent CARMA1 recruitment into BCL10-containing complexes in Jurkat cells. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:17948050 Malt1 ubiquitination triggers NF-kappaB signaling upon T-cel... | KEEP AS NON CORE | Summary: CARD11 and MALT1 associate within the CBM signaling assembly. Reason: Authenticated fuller source Results show CARMA1 recruitment to BCL10βMALT1 complexes. Preserve the experimental association under the standing binding policy, with co-complex rather than independently purified CARD11βMALT1 binary contact as the evidence level. The available assembly places MALT1 with BCL10; no separate CARD11 protease-binding or protease-regulator activity is inferred solely from this coassociation. |
| GO:0005515 protein binding | IPI PMID:19118383 Casein kinase 1alpha governs antigen-receptor-induced NF-kap... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The source demonstrates stimulated CBM association and distinguishes it from CK1alpha regulation. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:19118383 Casein kinase 1alpha governs antigen-receptor-induced NF-kap... | MODIFY | Summary: CARD11 binds the protein kinase CK1alpha. Reason: The source maps selective CARMA1 association with CK1alpha using cellular co-immunoprecipitation and terminal/deletion constructs. Protein kinase binding is a supported narrower description of this association; phosphorylation is performed by CK1alpha, not CARD11. The exact P48729 and P48729-1 partner records remain separate without a claim of isoform-exclusive binding. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19118383 Casein kinase 1alpha governs antigen-receptor-induced NF-kap... | MODIFY | Summary: CARD11 binds the protein kinase CK1alpha. Reason: The source maps selective CARMA1 association with CK1alpha using cellular co-immunoprecipitation and terminal/deletion constructs. Protein kinase binding is a supported narrower description of this association; phosphorylation is performed by CK1alpha, not CARD11. The exact P48729 and P48729-1 partner records remain separate without a claim of isoform-exclusive binding. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19444310 COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upo... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The indexed primary Figure 2C explicitly demonstrates stimulus-dependent BCL10βCARMA1 association in Jurkat cells, despite the paper focusing on COP9. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:19706536 Phosphorylation of CARMA1 by HPK1 is critical for NF-kappaB ... | MODIFY | Summary: CARD11 associates with the protein kinase HPK1/MAP4K1. Reason: The primary Results/Figure 2 report CARMA1βHPK1 co-immunoprecipitation and domain mapping, consistent with the complete abstract. Preserve the literal P70218 mouse Map4k1 partner, explicitly marked Xeno by UniProt, rather than silently replacing it with human MAP4K1. Refine to protein kinase binding without transferring catalytic kinase activity to the phosphorylation substrate CARD11. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19815501 Mechanisms of NKT cell anergy induction involve Cbl-b-promot... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The primary Figure 5E assays CARMA1βBCL10 association in a human NKT-cell line, separate from the mouse knockout phenotypes. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:19815501 Mechanisms of NKT cell anergy induction involve Cbl-b-promot... | KEEP AS NON CORE | Summary: CARD11 associates with CBLB during regulation of the signaling complex. Reason: Primary Figure 5A/B reports transfected 293T and endogenous Jurkat CBLBβCARMA1 association. Retain the literal Q13191-1 interaction under the standing project binding policy, with the coassociation and regulatory context explicit. These experiments do not independently resolve a direct binary interface or establish CARD11 ubiquitin-ligase activity; mouse NKT phenotypes are not automatically human binding-assay outcomes. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21157432 Dephosphorylation of Carma1 by PP2A negatively regulates T-c... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: Selected primary Results and Figures 3, 4 and 6 show stimulated endogenous Jurkat CARMA1βBCL10 association and its regulation by PP2A. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:22528498 Protein kinase C-Ξ΄ negatively regulates T cell receptor-indu... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The complete available Discussion explicitly describes CARMA1βBCL10 association, although the canonical HTML lacks Results and Methods. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:22528498 Protein kinase C-Ξ΄ negatively regulates T cell receptor-indu... | MODIFY | Summary: CARD11 associates with protein kinase C-delta. Reason: The complete available source Discussion explicitly describes PKC-delta association with the CARMA1 MAGUK region and its effects on signalosome assembly. This supports the narrower protein kinase binding assignment with experimental-curator deference. The canonical HTML lacks Results/Methods, so pair-specific quantitative or purified binary binding is not claimed; CARD11 is not assigned PKC catalytic activity. Proposed replacements: protein kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22528498 Protein kinase C-Ξ΄ negatively regulates T cell receptor-indu... | KEEP AS NON CORE | Summary: CARD11 is associated with MALT1 in a regulated signalosome. Reason: The source Discussion reports CARMA1, BCL10 and MALT1 association and PKC-delta-dependent changes in complex assembly; original Results/Methods are absent from the canonical HTML. Preserve the supported curated co-complex association under the project binding policy, without upgrading it to an independently mapped direct CARD11βMALT1 protease-binding mechanism. |
| GO:0005515 protein binding | IPI PMID:27777308 Molecular Determinants of Scaffold-induced Linear Ubiquitiny... | MODIFY | Summary: CARD11 brings BCL10 substrate together with the HOIP enzyme. Reason: The source explicitly demonstrates scaffold-dependent co-recruitment, with endogenous stimulated Jurkat association and cellular deletion mapping. This supplies direct evidence for the existing signaling adaptor activity, rather than mere proximity or transfer of HOIP ubiquitin-ligase catalysis to CARD11. The refinement is part of the same integrated adaptor core, not a second independent catalytic function. Proposed replacements: signaling adaptor activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31296852 Structures of autoinhibited and polymerized forms of CARD9 r... | MODIFY | Summary: CARD11 recognizes BCL10 through CARD-mediated binding. Reason: The source directly assays human purified CARD11 constructs that template BCL10 assembly; its mammalian CARD11 reporter construct is mouse, and the resolved atomic structures are CARD9. Independent target CARD-interface and human biochemical studies establish the more informative existing CARD domain binding function for this same partner. Refine the broad binding assertion without claiming each original co-immunoprecipitation independently maps the interface or that every complex association is binary. Proposed replacements: CARD domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The exact CARD11βPTEN fragment-assay evidence remains unresolved. Reason: The original IPI edge is also recorded by UniProt, and the actual study uses recombinant PDZ domains and partner peptide motifs. However, the CARD11βPTEN target table, construct and affinity values were not recovered. Preserve the assertion and uncertainty rather than calling the interaction false. A CARD11 PDZ domain recognizing a partner peptide is not evidence that CARD11 binds a partner PDZ domain. The official correction restores figure labeling/layout; it does not establish or invalidate the unread target row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | UNDECIDED | Summary: The exact CARD11βRSK1 fragment-assay evidence remains unresolved. Reason: The original IPI edge is also recorded by UniProt, and the actual study uses recombinant PDZ domains and partner peptide motifs. However, the CARD11βRSK1 target table, construct and affinity values were not recovered. Preserve the assertion and uncertainty rather than calling the interaction false. A CARD11 PDZ domain recognizing a partner peptide is not evidence that CARD11 binds a partner PDZ domain. The official correction restores figure labeling/layout; it does not establish or invalidate the unread target row. Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:17287217 Caveolin-1 triggers T-cell activation via CD26 in associatio... | KEEP AS NON CORE | Summary: CARD11 occupies an intracellular signaling pool associated with CD26 signaling. Reason: The source explicitly places the CD26βCARMA1 interaction at the CD26 cytoplasmic tail and describes recruitment of the complex to lipid rafts. Retain the broad cytoplasm assignment with experimental-curator deference; it is not a claim of an exclusively diffuse soluble pool. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The conserved CARD11 signaling adaptor acts in the cytoplasm and at the cytoplasmic membrane surface. Reason: The PAINT assertion agrees with target signaling and localization evidence. The PTN node is preserved without claiming its uninspected placement was independently reconstructed; inclusion of CARD11 among descendant evidence is legitimate, not circular support. Cytoplasm remains a broad location. |
| GO:0005737 cytoplasm | IDA PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | KEEP AS NON CORE | Summary: CARD11 is an intracellular, membrane-associated signaling scaffold. Reason: The source describes CARD11 association with lipid rafts and receptor-induced BCL10 recruitment. The existing broad cytoplasm IDA assertion is compatible with this intracellular distribution and is retained under experimental-curator deference, without claiming that the abstract alone resolves every cytoplasmic subcompartment. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CARD11 has a cytoplasmic signaling location. Reason: The UniProt subcellular-location mapping is consistent with the independently established intracellular CBM adaptor. Broad cytoplasm includes the cytoplasmic side of membrane signaling sites; it should not be rewritten as exclusively free cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1168635 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes PRKCB-dependent phosphorylation of CARMA1 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202394 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes recruitment of CARMA1 to the plasma membrane and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202437 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes phosphorylation of CARMA1 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202443 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes CARMA1 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202453 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TRAF6 autoubiquitination and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202459 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes BCL10 phosphorylation and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202466 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes BCL10 association with CARMA1 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202472 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TRAF6 recruitment to the CBM complex and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202478 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes BCL10-associated MALT1 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202489 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes BCL10 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202500 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes IKK-complex activation and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202510 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TAK1βTAB2 activation and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202534 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TRAF6-dependent NEMO ubiquitination and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730861 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TAK1-complex recruitment to ubiquitinated TRAF6 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730863 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes PKC-theta-dependent phosphorylation of CARMA1 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730864 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes MALT1-mediated TRAF6 recruitment to the CBM complex and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730876 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TAK1-dependent IKK-beta phosphorylation and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730899 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes BCL10βMALT1 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730900 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes activation of TRAF6-associated TAK1 and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730902 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes phosphorylated CARMA1 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730903 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TRAF6 oligomerization and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730904 | KEEP AS NON CORE | Summary: CARD11 has a cytosolic pathway-associated pool. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol assignment. The complete cached event summary describes TRAF6 autoubiquitination and supplies pathway context, but does not independently resolve the distribution of soluble versus membrane-associated CARD11. Retain this contextual compartment; membership in the reaction pathway does not assign the reaction enzyme activity to CARD11. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane-associated CARD11 organizes antigen-receptor signaling. Reason: The PAINT location is independently supported by CARD11 raft association and recruitment of CBM components at the plasma membrane. This is an intracellular peripheral association, not a claim that CARD11 is a transmembrane receptor. The actual PTN placement was not independently inspected. |
| GO:0005886 plasma membrane | IDA PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | ACCEPT | Summary: CARD11 associates with the plasma-membrane signaling compartment. Reason: The source directly reports constitutive CARMA1 association with lipid rafts and receptor-induced association with TCR/BCL10. Retain the experimental membrane assignment; membrane association is central to its assembly function. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: CARD11 is a plasma-membrane-associated signaling adaptor. Reason: The combined automated and mouse-ortholog mapping is corroborated by target experimental membrane/raft evidence. The original ARBA and donor identifiers are preserved; no independent reconstruction of each rule is claimed. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1168635 | ACCEPT | Summary: CARD11 acts at membrane-associated antigen-receptor signaling sites. Reason: The curated event describes PKC-beta phosphorylation in the B-cell receptor pathway. Its membrane assignment is independently consistent with the target raft/localization evidence. CARD11 contributes the assembly platform; phosphorylation is performed by the upstream kinase. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1168644 | ACCEPT | Summary: CARD11 acts at membrane-associated antigen-receptor signaling sites. Reason: The curated event describes recruitment of BCL10 and MALT1 into a membrane-associated CBM complex. Its membrane assignment is independently consistent with the target raft/localization evidence. CARD11 contributes the assembly platform; phosphorylation is performed by the upstream kinase. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2730863 | ACCEPT | Summary: CARD11 acts at membrane-associated antigen-receptor signaling sites. Reason: The curated event describes PKC-theta phosphorylation in the T-cell receptor pathway. Its membrane assignment is independently consistent with the target raft/localization evidence. CARD11 contributes the assembly platform; phosphorylation is performed by the upstream kinase. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CARD11 transmits receptor signals through an organized protein assembly. Reason: The PAINT inference is consistent with direct BCL10 nucleation and regulated assembly of downstream signaling components. Broad signal transduction is retained because CARD11 has multiple signaling outputs; the core is expressed by the existing signaling-adaptor and NF-kappaB annotations. The PTN and legitimate target descendant support are preserved without an invented phylogenetic defect. |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CARD11 is a signal-transduction adaptor. Reason: The broad ARBA assertion is supported by target biochemical assembly and cellular receptor-signaling assays. It is informative as context but does not specify a catalytic reaction or imply every downstream pathway is a separate core function. |
| GO:0007249 canonical NF-kappaB signal transduction | IDA PMID:24074955 Structural architecture of the CARMA1/Bcl10/MALT1 signalosom... | ACCEPT | Summary: CARD11 nucleates a CBM signaling assembly that activates canonical NF-kappaB. Reason: Human recombinant CARMA1/BCL10 experiments and cellular assembly/reporter assays support actual structural work in this pathway. The 2013 and 2019 studies differ in their interpretation of the effective small-oligomer versus filamentous template, but both establish target assembly and BCL10 nucleation. CARD11 is not assigned the MALT1 protease or IKK kinase reaction. |
| GO:0007249 canonical NF-kappaB signal transduction | IMP PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | ACCEPT | Summary: CARD11 couples TCR stimulation to canonical NF-kappaB activation. Reason: The source reports receptor-induced CARMA1/TCR/BCL10 association and inhibition of NF-kappaB by a BCL10-binding-defective CARMA1 mutant. Direct assembly evidence independently establishes how CARD11 performs work in the signaling pathway. |
| GO:0007249 canonical NF-kappaB signal transduction | IMP PMID:28628108 Germline hypomorphic CARD11 mutations in severe atopic disea... | ACCEPT | Summary: Human CARD11 supports canonical NF-kappaB signaling in lymphocytes. Reason: The full primary study tests human CARD11 variants in wild-type and CARD11-deficient Jurkat cells and measures impaired patient lymphocyte NF-kappaB responses. Defective BCL10/MALT1 recruitment provides a target mechanism beyond necessity alone. The corrigendum changes author, affiliation and acknowledgment information; the available correction prose does not withdraw these experiments. |
| GO:0031295 T cell costimulation | IDA PMID:17287217 Caveolin-1 triggers T-cell activation via CD26 in associatio... | KEEP AS NON CORE | Summary: CARD11 helps transmit CD26-associated T-cell costimulatory signals. Reason: The source directly describes CD26-tail association with CARMA1 and recruitment of CD26/CARMA1/BCL10/IKK to rafts following caveolin-1 ligation, with TCR/CD3-dependent costimulation. Retain the experimentally curated process as a receptor-context output of the adaptor, without treating CARD11 as the extracellular ligand or assigning all caveolin functions to it. Supporting Evidence: |
| GO:0032449 CBM complex | IDA PMID:24074955 Structural architecture of the CARMA1/Bcl10/MALT1 signalosom... | ACCEPT | Summary: CARD11 is the nucleating adaptor of the CARMA1βBCL10βMALT1 signalosome. Reason: Purified human CARMA1 and BCL10 constructs support reconstitution of the CBM assembly, with MALT1 associated with BCL10 and CARMA1 at the nucleating end; cell experiments corroborate assembly. The precise physiological oligomer size is not fixed by these preparations. Supporting Evidence: |
| GO:0032449 CBM complex | IDA PMID:28628108 Germline hypomorphic CARD11 mutations in severe atopic disea... | ACCEPT | Summary: CARD11 associates with BCL10 and MALT1 in the CBM complex. Reason: Human CARD11 expression and stimulated Jurkat BCL10 co-immunoprecipitation directly assess complex assembly; disease-associated variants reduce association. Reduced MALT1-dependent CYLD cleavage is a downstream functional readout, not CARD11 protease activity. Supporting Evidence: |
| GO:0032449 CBM complex | IPI PMID:19118383 Casein kinase 1alpha governs antigen-receptor-induced NF-kap... | ACCEPT | Summary: CARD11 participates in the antigen-receptor-induced CBM complex. Reason: The study identifies CK1alpha recruitment to CARMA1/BCL10/MALT1 and tests stimulated human lymphocyte-cell-line complexes and CARMA1 constructs. This supports membership of CARD11 in the complex while distinguishing complex coassociation from every possible binary contact. |
| GO:0032743 positive regulation of interleukin-2 production | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CARD11 signaling promotes T-cell IL-2 production. Reason: The ARBA process is independently corroborated by direct target mutant experiments linking BCL10 recruitment to receptor-induced IL-2 production. IL-2 production is an output of the signaling adaptor, not a separate enzymatic activity of CARD11. Supporting Evidence: |
| GO:0032743 positive regulation of interleukin-2 production | IMP PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | KEEP AS NON CORE | Summary: CARD11-dependent TCR signaling promotes IL-2 production. Reason: A CARMA1 mutant defective in BCL10 binding inhibits receptor-induced IL-2 production in the cited study. Retain this experimentally supported cellular output, with direct assembly supplying the mechanistic connection and without making CARD11 a transcription factor. Supporting Evidence: |
| GO:0035591 signaling adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: CARD11 organizes signaling proteins into a functional receptor-responsive assembly. Reason: This fits the official signaling-adaptor definition: CARD11 nucleates BCL10 and recruits signaling partners, including bringing BCL10 substrate together with the HOIP ubiquitin ligase. Target biochemical and cellular evidence independently corroborates the PAINT functional inference; the actual ancestral-node placement has not been inspected. No kinase, protease or ubiquitin-ligase catalysis is transferred from the recruited proteins. |
| GO:0038202 TORC1 signaling | IMP PMID:28628108 Germline hypomorphic CARD11 mutations in severe atopic disea... | KEEP AS NON CORE | Summary: CARD11 supports activation-associated TORC1 signaling in T cells. Reason: The source tests human CARD11 variants and patient T cells, showing reduced phospho-S6, impaired activation-associated ASCT2 upregulation and partial restoration of phospho-S6 by glutamine. Preserve the experimental pathway assertion as a contextual signaling output. The precise CARD11βASCT2 coupling mechanism remains unresolved; these data do not demonstrate direct transporter binding, glutamine transport by CARD11, or TOR kinase activity. Supporting Evidence: |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: A general CARD-domain mapping overextends the demonstrated CARD11 signaling role to an apoptotic process. Reason: The source transfers GO:0042981 from InterPro:IPR001315 CARD-domain membership. The original target study PMID:11278692 demonstrates selective CARD-mediated BCL10 recognition and NF-kappaB signaling, not an apoptotic endpoint. The selected human lymphoma experiments in PMID:19118383 establish signaling-dependent viability but do not distinguish apoptotic death from other loss of viability. Applying the apoptosis process to this target from domain membership alone therefore exceeds the resolved biological role of that domain. MARK_AS_OVER_ANNOTATED challenges this electronic transfer, not every possible apoptosis-related effect of CARD11. The actual term covers modulation of apoptotic death and does not require apoptosome membership or direct execution; context-specific regulation remains plausible and is retained as an experimental question. |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | NAS PMID:19118383 Casein kinase 1alpha governs antigen-receptor-induced NF-kap... | ACCEPT | Summary: CARD11 is a regulated organizer of canonical NF-kappaB signaling. Reason: The source directly connects CARMA1/CBM assembly to antigen-receptor NF-kappaB signaling and identifies both a positive CK1alpha-associated scaffold role and inhibitory phosphorylation of CARMA1. This broad regulation term is sound for CARD11, while kinase activity belongs to CK1alpha. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: CARD11 promotes canonical NF-kappaB activation through signalosome assembly. Reason: The PAINT inference agrees with direct target BCL10 nucleation, receptor-induced complex formation and NF-kappaB assays. Preserve the ancestral node and target descendant evidence without interpreting self-presence as circularity; no unsupported loss or misplacement is asserted. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000120 | ACCEPT | Summary: CARD11 positively regulates canonical NF-kappaB signaling. Reason: The combined automated and ortholog sources are corroborated by human CARD11 biochemical and cellular experiments. CARD11 supplies assembly and substrateβenzyme recruitment that advances signaling, rather than merely being a correlated disease marker. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | ACCEPT | Summary: CARD11 promotes receptor-induced canonical NF-kappaB activation. Reason: The target BCL10-binding-defective mutant interferes with TCR-induced NF-kappaB; independent reconstitution establishes the physical nucleation mechanism underlying this positive role. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse-to-human transfer of positive NF-kappaB regulation is supported by human target evidence. Reason: The original mouse Q8CIS0 source is retained. Human CARMA1 biochemical nucleation and human CARD11 variant/cellular signaling experiments independently establish the conserved positive function; the exact original donor experiment has not been independently reconstructed. |
| GO:0045121 membrane raft | IDA PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | ACCEPT | Summary: Lipid rafts are a functional membrane compartment for CARD11 signaling. Reason: The complete source abstract directly states CARMA1 raft association and distinguishes constitutive CARMA1 localization from stimulus-induced BCL10 recruitment. Retain the experimental compartment; no membrane-spanning topology is implied. Supporting Evidence: |
| GO:0045121 membrane raft | IDA PMID:17287217 Caveolin-1 triggers T-cell activation via CD26 in associatio... | ACCEPT | Summary: CARD11 is recruited with costimulatory signaling components to lipid rafts. Reason: The source explicitly describes recruitment of CD26, CARMA1, BCL10 and IKK to lipid rafts following CD26 ligation. This is target-containing localization evidence, not transfer of caveolin localization solely through association. Supporting Evidence: |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt raft mapping is corroborated by target experiments. Reason: Independent source abstracts directly support CARMA1 raft association and recruitment of its complex. Retain the subcellular-location mapping as a functional membrane context. |
| GO:0046037 GMP metabolic process | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: The GMP metabolic assertion inherits the unsupported catalytic specificity of its premise. Reason: GO_REF:0000108 derives this annotation from GO:0004385. The ontology relationship is appropriate for a GMP kinase, but the actual CARD11 primary Methods, Results and Discussion in PMID:11278692 establish GUK homology and BCL10/NF-kappaB scaffold activity without demonstrating ATP-dependent GMP-to-GDP turnover. The derived process contributes no independent metabolic evidence, so its specificity is over-annotated with the upstream activity. This is a source-to-function scope judgment, not a claim of demonstrated catalytic inactivity; neither protein phosphorylation nor another MAGUK's behavior supplies a CARD11 nucleotide assay. Supporting Evidence: |
| GO:0046710 GDP metabolic process | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: The GDP metabolic assertion inherits the unsupported catalytic specificity of its premise. Reason: GO_REF:0000108 derives this annotation from GO:0004385. The ontology relationship is appropriate for a GMP kinase, but the actual CARD11 primary Methods, Results and Discussion in PMID:11278692 establish GUK homology and BCL10/NF-kappaB scaffold activity without demonstrating ATP-dependent GMP-to-GDP turnover. The derived process contributes no independent metabolic evidence, so its specificity is over-annotated with the upstream activity. This is a source-to-function scope judgment, not a claim of demonstrated catalytic inactivity; neither protein phosphorylation nor another MAGUK's behavior supplies a CARD11 nucleotide assay. Supporting Evidence: |
| GO:0050700 CARD domain binding | IPI PMID:11278692 CARD11 and CARD14 are novel caspase recruitment domain (CARD... | ACCEPT | Summary: CARD11 recognizes the CARD domain of BCL10. Reason: The original primary abstract explicitly reports CARD11/CARD14 CARD-domain interaction with BCL10 and subsequent NF-kappaB activation. Human CARD11/BCL10 reconstitution and interface experiments independently support the target-specific CARD-mediated interaction. This term describes the recognized partner domain, not merely the presence of a CARD within CARD11. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CARD11 positively transmits T-cell receptor signals. Reason: The PAINT assertion is independently supported by receptor-responsive CARD11 complex assembly, mutant interference and downstream NF-kappaB activation. CARD11 performs adaptor work in this pathway; the uninspected PTN placement is preserved without a fabricated propagation defect. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: CARD11 supports T-cell receptor signaling through CBM assembly. Reason: The automated and mouse-ortholog transfer is corroborated by human target mutant and biochemical experiments. This existing process assignment reflects CARD11 organization of signaling components; it does not attribute the TCR receptor activity itself to CARD11. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | IMP PMID:12154360 CARMA1 is a critical lipid raft-associated regulator of TCR-... | ACCEPT | Summary: CARD11 promotes receptor-induced T-cell signaling. Reason: The source tests CARMA1βBCL10 coupling and shows that disrupting that interaction blocks TCR-induced NF-kappaB and IL-2 responses. Direct assembly explains the positive contribution. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Human CARD11 shares the mouse adaptor role in TCR signaling. Reason: The exact Q8CIS0 donor identity and ISS source are retained, and independent human CARD11 reporter, complex-assembly and patient-cell results support the transferred process. The original mouse experiment is not claimed to have been re-read. |
| GO:0050870 positive regulation of T cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CARD11 signaling promotes T-cell activation. Reason: The broad ARBA process is independently consistent with receptor-induced signaling and impaired activation responses in human variant-bearing T cells. It is retained as a cellular outcome of the same adaptor unit rather than a second molecular function. |
| GO:0051260 protein homooligomerization | IDA PMID:24074955 Structural architecture of the CARMA1/Bcl10/MALT1 signalosom... | ACCEPT | Summary: CARD11 self-association generates a platform for BCL10 nucleation. Reason: Purified human CARMA1 fragments form oligomers and seed BCL10 assembly in the 2013 study. The 2019 target experiments refine the active template toward a filamentous assembly rather than a generic small oligomer. Both support self-association, without fixing the stoichiometry of native full-length CARD11. |
| GO:0051260 protein homooligomerization | IDA PMID:31296852 Structures of autoinhibited and polymerized forms of CARD9 r... | ACCEPT | Summary: Human CARD11 fragments form BCL10-templating assemblies. Reason: The source directly assays purified human CARD11 constructs and distinguishes active filament-containing fractions from inactive small oligomers, with concentration and preparation limits. Its mammalian reporter CARD11 constructs use mouse sequence, and CARD9 supplies the resolved atomic structures; those results are not presented as an atomic structure of human CARD11. |
| GO:0070062 extracellular exosome | HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ... | KEEP AS NON CORE | Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Cytoplasmic/membrane-raft signalling scaffold. Cytosolic protein (UniProt); cytosolic proteins, including abundant enzymes and cytoskeletal proteins, are expected and often promiscuous EV contents (MISEV2018 (PMID:30637094) category 2b). True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.) Supporting Evidence: |
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Download this section (compressed HTML)Q: Does purified, correctly folded full-length human CARD11 or its GUK domain catalyze GMP phosphorylation, with nucleotide-product identification and suitable positive and negative controls? The inspected historical source does not establish this chemistry; the over-annotation judgment does not establish catalytic inactivity.
Q: Which defined apoptotic pathway, if any, is directly regulated by CARD11 in a target-specific experiment, rather than inferred from CARD architecture or transformed-cell viability?
Q: Which CARD11 peptides and vesicle-purification controls support the neural-stem-cell extracellular-exosome assertion?
Q: What is the active full-length CARD11 assembly in native lymphocytes, and how do small-oligomer and filament preparations relate to that state?
Q: What molecular step connects CARD11 to ASCT2-dependent nutrient signaling in human T cells? Reduced transporter upregulation and phospho-S6 do not establish a direct binary interface.
Experiment: Reconstitute full-length CARD11-dependent BCL10 assembly with defined phosphorylation state and native-membrane recruitment, comparing oligomer distributions and NF-kappaB pathway output.
Experiment: Test nucleotide turnover by purified CARD11 with mass-spectrometric or chromatographic GDP identification, matched folding controls and an authentic guanylate kinase positive control.
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Download this section (compressed HTML)Loading supporting contentβ¦
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