CASP1 (caspase-1; interleukin-1 beta converting enzyme, ICE) is the prototypical inflammatory caspase, a cysteine-dependent aspartate-specific endopeptidase of the clan CD peptidase family. It is expressed mainly in monocytes, macrophages and other immune cells and is synthesized as an inactive cytosolic zymogen comprising an N-terminal caspase-recruitment domain (CARD), a large (p20) catalytic subunit bearing the His/Cys catalytic dyad, an interdomain linker, and a small (p10) subunit. The active enzyme is a heterotetramer of two antiparallel p20/p10 heterodimers. Caspase-1 is the effector protease of canonical inflammasomes: cytosolic pattern-recognition receptors (NLRP1, NLRP3, NLRC4/NAIP, AIM2, pyrin) assemble, directly or through the bipartite adaptor ASC/PYCARD, into platforms that cluster procaspase-1 via homotypic CARD-CARD interactions, driving proximity-induced autoproteolysis and activation. Once active, caspase-1 cleaves the precursors of the proinflammatory cytokines interleukin-1 beta and interleukin-18 into their mature, secreted, receptor-binding forms, and cleaves gasdermin-D to release its pore-forming N-terminal fragment, which permeabilizes the plasma membrane to drive the lytic, proinflammatory cell death pyroptosis and the release of mature IL-1 family cytokines. Caspase-1 also processes additional substrates (including caspase-7, cGAS, sphingosine kinase 2 and ZNFX1) and contributes to apoptosis in some overexpression and disease contexts. It acts in the cytosol and is central to innate immune defense against microbial infection and to the pathology of autoinflammatory diseases.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:21918512 The NLRC4 inflammasome receptors for bacterial flagellin and... | MODIFY | Summary: CASP1 is the effector protease downstream of pattern-recognition receptors, not itself a PRR. Reason: These NAS annotations place CASP1 in PRR signalling because inflammasomes act downstream of cytosolic PRRs. CASP1 does not bind a PAMP/DAMP; it is the terminal protease of the inflammasome. The precise term is inflammasome-mediated signaling pathway (GO:0141084), whose definition is "starts with a ligand binding to a PRR, assembly of the inflammasome complex, leading to the activation of CASP1". Proposed replacements: inflammasome-mediated signaling pathway Supporting Evidence: PMID:29196474 Inflammasome activation and assembly at a glance |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:22258606 Inflammasomes in health and disease. | MODIFY | Summary: CASP1 is the effector protease downstream of pattern-recognition receptors, not itself a PRR. Reason: These NAS annotations place CASP1 in PRR signalling because inflammasomes act downstream of cytosolic PRRs. CASP1 does not bind a PAMP/DAMP; it is the terminal protease of the inflammasome. The precise term is inflammasome-mediated signaling pathway (GO:0141084), whose definition is "starts with a ligand binding to a PRR, assembly of the inflammasome complex, leading to the activation of CASP1". Proposed replacements: inflammasome-mediated signaling pathway Supporting Evidence: PMID:29196474 Inflammasome activation and assembly at a glance |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:29196474 Inflammasome activation and assembly at a glance. | MODIFY | Summary: CASP1 is the effector protease downstream of pattern-recognition receptors, not itself a PRR. Reason: These NAS annotations place CASP1 in PRR signalling because inflammasomes act downstream of cytosolic PRRs. CASP1 does not bind a PAMP/DAMP; it is the terminal protease of the inflammasome. The precise term is inflammasome-mediated signaling pathway (GO:0141084), whose definition is "starts with a ligand binding to a PRR, assembly of the inflammasome complex, leading to the activation of CASP1". Proposed replacements: inflammasome-mediated signaling pathway Supporting Evidence: PMID:29196474 Inflammasome activation and assembly at a glance |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:29247998 The AIM2 inflammasome: Sensor of pathogens and cellular pert... | MODIFY | Summary: CASP1 is the effector protease downstream of pattern-recognition receptors, not itself a PRR. Reason: These NAS annotations place CASP1 in PRR signalling because inflammasomes act downstream of cytosolic PRRs. CASP1 does not bind a PAMP/DAMP; it is the terminal protease of the inflammasome. The precise term is inflammasome-mediated signaling pathway (GO:0141084), whose definition is "starts with a ligand binding to a PRR, assembly of the inflammasome complex, leading to the activation of CASP1". Proposed replacements: inflammasome-mediated signaling pathway Supporting Evidence: PMID:29196474 Inflammasome activation and assembly at a glance |
| GO:0004175 endopeptidase activity | IDA PMID:24548080 CDK5 protects from caspase-induced Ataxin-3 cleavage and neu... | MODIFY | Summary: Generic endopeptidase activity; CASP1 is specifically a cysteine-type (clan CD) endopeptidase. Reason: The IDA (CDK5/Ataxin-3 caspase-cleavage paper) supports endopeptidase activity but the informative term is the cysteine-type child GO:0004197, which CASP1 carries with abundant direct evidence. Generalize to the specific activity. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:24548080 increased caspase-dependent Ataxin-3 cleavage |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:15326478 A novel isoform of pro-interleukin-18 expressed in ovarian t... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:1574116 A novel heterodimeric cysteine protease is required for inte... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:2787508 Identification of a monocyte specific pre-interleukin 1 beta... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:32553275 Caspase-1 Engages Full-Length Gasdermin D through Two Distin... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:39333773 The human disease-associated gene ZNFX1 controls inflammatio... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9334240 Involvement of caspase-1 and caspase-3 in the production and... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | IGI PMID:15882992 Nucleotide binding to CARD12 and its role in CARD12-mediated... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0004197 cysteine-type endopeptidase activity | TAS PMID:10353249 Inhibition of caspase-1 slows disease progression in a mouse... | ACCEPT | Summary: Core molecular function: CASP1 is a cysteine-dependent, Asp-specific endopeptidase, the effector protease of inflammasomes. Reason: Extensively supported by direct assays and the phylogenetic IBA. CASP1 was purified and cloned as a heterodimeric cysteine protease that matures pro-IL-1beta, and its catalytic residues (His237/Cys285) and p20/p10 architecture are established. This is the defining activity of the gene product. Supporting Evidence: PMID:1574116 A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes PMID:32109412 The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 |
| GO:0005515 protein binding | IPI PMID:11374873 Human CARD12 is a novel CED4/Apaf-1 family member that induc... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:11390368 Identification of Ipaf, a human caspase-1-activating protein... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:11432859 Cop, a caspase recruitment domain-containing protein and inh... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15107016 Heterotypic interactions among NACHT domains: implications f... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15107016 Heterotypic interactions among NACHT domains: implications f... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15107016 Heterotypic interactions among NACHT domains: implications f... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15383541 INCA, a novel human caspase recruitment domain protein that ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:15817483 PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedbac... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:16575408 The estrogen-responsive B box protein: a novel enhancer of i... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:16785446 The B30.2 domain of pyrin, the familial Mediterranean fever ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:16785446 The B30.2 domain of pyrin, the familial Mediterranean fever ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:17360653 NF-kappaB activation by the Toll-IL-1 receptor domain protei... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:17418785 Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activati... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:17418785 Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activati... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:18329368 Active caspase-1 is a regulator of unconventional protein se... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:18329368 Active caspase-1 is a regulator of unconventional protein se... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:18511561 A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta s... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:18511561 A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta s... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:25605870 Syk is involved in NLRP3 inflammasome-mediated caspase-1 act... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:27043298 Molecular basis of caspase-1 polymerization and its inhibiti... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:27043298 Molecular basis of caspase-1 polymerization and its inhibiti... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:30692621 SERPINB1-mediated checkpoint of inflammatory caspase activat... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:31421660 Expression of a PYCARD/ASC variant lacking exon 2 in Japanes... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI P29466-3 PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:34296442 SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocki... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005515 protein binding | IPI PMID:34589402 Lonicerin targets EZH2 to alleviate ulcerative colitis by au... | REMOVE | Summary: Bare protein binding from many pairwise interaction studies; uninformative as a molecular function. Reason: Per curation guidance, generic protein binding is not retained. Many of the underlying interactions are biologically real (ASC/PYCARD, NLRC4, NLRP1, NOD2, MEFV, CARD16/17/18, SERPINB1, GSDMD, VAC14) but each is captured by a specific complex, process, or CARD-domain-binding annotation elsewhere in this set. No more informative molecular function is supportable from the bare term, so it is removed rather than rewritten. |
| GO:0005730 nucleolus | NAS PMID:28263976 NLRP1 promotes tumor growth by enhancing inflammasome activa... | MARK AS OVER ANNOTATED | Summary: Nucleolar localization asserted from a paper reporting NLRP1 (not CASP1) in the nucleolus. Reason: The cited melanoma study reports NLRP1 primarily in the nucleolus of THP-1 cells; it does not demonstrate nucleolar CASP1. The NAS inference is not supported for caspase-1. Supporting Evidence: PMID:28263976 NLRP1 is primarily in the nucleolus of THP-1 cells |
| GO:0005737 cytoplasm | IDA PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its r... | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005737 cytoplasm | NAS PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005737 cytoplasm | NAS PMID:24803432 Inflammasome activation causes dual recruitment of NLRC4 and... | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005737 cytoplasm | NAS PMID:28263976 NLRP1 promotes tumor growth by enhancing inflammasome activa... | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005737 cytoplasm | TAS PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | ACCEPT | Summary: Cytoplasm (general cytosolic localization). Reason: Consistent with the cytosol annotation; CASP1 is a cytoplasmic protein. The cytosol child is the more precise statement. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | IDA PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its r... | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | IDA PMID:39333773 The human disease-associated gene ZNFX1 controls inflammatio... | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448673 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448678 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448702 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-448703 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6798081 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844612 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844617 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012542 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012556 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9012689 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9647680 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9731057 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956714 | ACCEPT | Summary: Cytosol: the compartment where the inflammasome assembles and CASP1 is active. Reason: CASP1 is a cytosolic enzyme; inflammasome assembly and caspase-1 activation occur in the cytosol. Supported by IDA and the Reactome pathway annotations. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 |
| GO:0005874 microtubule | NAS PMID:27911804 Familial Mediterranean fever mutations lift the obligatory r... | MARK AS OVER ANNOTATED | Summary: Microtubule localization asserted from a paper about pyrin, not CASP1. Reason: The cited study shows that microtubules control pyrin-mediated caspase-1 activation; it does not localize CASP1 itself to microtubules. The NAS inference over-reaches. I cannot verify a direct CASP1 microtubule localization, so this is flagged as over-annotation. Supporting Evidence: PMID:27911804 wild-type and FMF Pyrin are differentially controlled by microtubules |
| GO:0005886 plasma membrane | EXP PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its r... | KEEP AS NON CORE | Summary: Plasma-membrane pool associated with secretion/release during cell death. Reason: A cell-membrane fraction of caspase-1 was reported alongside its cytoplasmic localization (UniProt records both from the SPHK2 study). Minor relative to the cytosolic inflammasome pool. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plasma-membrane pool associated with secretion/release during cell death. Reason: A cell-membrane fraction of caspase-1 was reported alongside its cytoplasmic localization (UniProt records both from the SPHK2 study). Minor relative to the cytosolic inflammasome pool. Supporting Evidence: PMID:20197547 Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells |
| GO:0006508 proteolysis | IDA PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary... | ACCEPT | Summary: Proteolysis: the activity class of CASP1 as a protease. Reason: CASP1 is a protease; proteolysis is the correct (general) biological-process annotation. The specific substrate-processing children are more informative. Supporting Evidence: PMID:7876192 interleukin-1 beta converting enzyme |
| GO:0006508 proteolysis | IDA PMID:24548080 CDK5 protects from caspase-induced Ataxin-3 cleavage and neu... | ACCEPT | Summary: Proteolysis: the activity class of CASP1 as a protease. Reason: CASP1 is a protease; proteolysis is the correct (general) biological-process annotation. The specific substrate-processing children are more informative. Supporting Evidence: PMID:7876192 interleukin-1 beta converting enzyme |
| GO:0006508 proteolysis | IEA GO_REF:0000120 | ACCEPT | Summary: Proteolysis: the activity class of CASP1 as a protease. Reason: CASP1 is a protease; proteolysis is the correct (general) biological-process annotation. The specific substrate-processing children are more informative. Supporting Evidence: PMID:7876192 interleukin-1 beta converting enzyme |
| GO:0006508 proteolysis | TAS PMID:7876192 Cloning and expression of four novel isoforms of human inter... | ACCEPT | Summary: Proteolysis: the activity class of CASP1 as a protease. Reason: CASP1 is a protease; proteolysis is the correct (general) biological-process annotation. The specific substrate-processing children are more informative. Supporting Evidence: PMID:7876192 interleukin-1 beta converting enzyme |
| GO:0006915 apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Apoptotic process: overexpressed CASP1/ICE isoforms can induce apoptosis. Reason: ICE and its isoforms induce apoptosis when overexpressed, and caspase-1 participates in some apoptotic/neurodegeneration contexts. Real but pleiotropic and not the physiological core (cytokine maturation/pyroptosis). Supporting Evidence: PMID:7876192 only the parental ICE alpha and isoforms beta and gamma, but not isoforms delta and epsilon, can induce apoptosis when overexpressed in Sf9 insect cells |
| GO:0006915 apoptotic process | TAS PMID:7876192 Cloning and expression of four novel isoforms of human inter... | KEEP AS NON CORE | Summary: Apoptotic process: overexpressed CASP1/ICE isoforms can induce apoptosis. Reason: ICE and its isoforms induce apoptosis when overexpressed, and caspase-1 participates in some apoptotic/neurodegeneration contexts. Real but pleiotropic and not the physiological core (cytokine maturation/pyroptosis). Supporting Evidence: PMID:7876192 only the parental ICE alpha and isoforms beta and gamma, but not isoforms delta and epsilon, can induce apoptosis when overexpressed in Sf9 insect cells |
| GO:0006954 inflammatory response | IEA GO_REF:0000117 | ACCEPT | Summary: Inflammatory response (IEA). Reason: CASP1 is a central driver of the inflammatory response through maturation of IL-1beta/IL-18 and pyroptosis. The generic term is correct; positive regulation of inflammatory response is the more specific statement CASP1 also carries. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0007165 signal transduction | TAS PMID:1373520 Molecular cloning of the interleukin-1 beta converting enzym... | MODIFY | Summary: Over-general signal transduction (from the original cloning paper). Reason: CASP1 acts within inflammasome signalling; the generic signal-transduction term is uninformative and better represented by inflammasome-mediated signaling pathway (GO:0141084). Proposed replacements: inflammasome-mediated signaling pathway Supporting Evidence: PMID:1373520 Molecular cloning of the interleukin-1 beta converting enzyme |
| GO:0007231 osmosensory signaling pathway | NAS PMID:22981536 Cell volume regulation modulates NLRP3 inflammasome activati... | MARK AS OVER ANNOTATED | Summary: Osmosensory signaling pathway: CASP1 is activated by cell swelling but does not sense osmolarity. Reason: Hypo-osmotic cell swelling activates the NLRP3 inflammasome and thereby caspase-1; the osmosensing is performed upstream (K+ flux, NLRP3), not by CASP1. CASP1 is downstream, so the involved_in claim over-reaches. Supporting Evidence: PMID:22981536 a decrease in extracellular osmolarity induced a K(+)-dependent conformational change of the preassembled NLRP3-inactive inflammasome |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: Over-general cysteine-type peptidase activity (IEA). Reason: CASP1 is an endopeptidase; the specific and well-evidenced term is GO:0004197 cysteine-type endopeptidase activity. Replace the broad InterPro2GO electronic term with the specific one. Proposed replacements: cysteine-type endopeptidase activity Supporting Evidence: PMID:1574116 a unique cysteine protease |
| GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process | TAS PMID:10799503 The prodomain of caspase-1 enhances Fas-mediated apoptosis t... | MARK AS OVER ANNOTATED | Summary: The caspase-1 prodomain enhances Fas-mediated apoptosis, probably by facilitating caspase-8 activation; a direct cysteine-type endopeptidase activator activity of caspase-1 is not established, so the term is over-annotated. Reason: The caspase-1 prodomain enhances Fas-mediated apoptosis by facilitating caspase-8 activation. A documented but accessory activity, distinct from the core IL-1 maturation role. Splitting the precomposed term shows the genus, a direct caspase-activator activity, is not established: the source says the caspase-1 prodomain enhances Fas-mediated apoptosis "most probably" by facilitating caspase-8 activation, a hedged and indirect effect. Treated like BCL2L13's equally hedged row, as over-annotated rather than modified. Supporting Evidence: PMID:10799503 Pro-C1 acts to enhance Fas-mediated apoptosis, most probably through facilitation of the activation of caspase-8 |
| GO:0016485 protein processing | IBA GO_REF:0000033 | ACCEPT | Summary: Protein processing (IBA); general parent covering cytokine maturation, GSDMD cleavage and autoprocessing. Reason: A correct phylogenetic assertion at a general level. The specific children (cytokine precursor processing, protein autoprocessing, protein maturation) are the more informative statements CASP1 also carries. Supporting Evidence: PMID:1574116 derived from a single proenzyme, possibly by autoproteolysis |
| GO:0016540 protein autoprocessing | IDA PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: Protein autoprocessing: CASP1 cleaves its own interdomain linker to generate the active p20/p10 enzyme. Reason: Autoproteolysis in the interdomain linker is required for catalytic activity and pyroptosis. This is the substrate-is-the-enzyme autoprocessing case (parent GO:0006508 proteolysis). Supporting Evidence: PMID:32109412 site-specific caspase-4/11 autoprocessing, generating a p10 product, is required and sufficient for cleaving GSDMD PMID:11821383 CARD-8 protein, a new CARD family member that regulates caspase-1 activation |
| GO:0016540 protein autoprocessing | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Protein autoprocessing: CASP1 cleaves its own interdomain linker to generate the active p20/p10 enzyme. Reason: Autoproteolysis in the interdomain linker is required for catalytic activity and pyroptosis. This is the substrate-is-the-enzyme autoprocessing case (parent GO:0006508 proteolysis). Supporting Evidence: PMID:32109412 site-specific caspase-4/11 autoprocessing, generating a p10 product, is required and sufficient for cleaving GSDMD PMID:11821383 CARD-8 protein, a new CARD family member that regulates caspase-1 activation |
| GO:0019899 enzyme binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: Bare enzyme binding (IEA), uninformative. Reason: Electronic enzyme-binding annotation adds no functional information. The specific, evidence-backed interactions (CARD domain binding GO:0050700, RIP2 kinase binding GO:0019900) capture what is known. Removal does not imply any interaction is false. TOO_GENERAL rather than REMOVE: kinase binding, kept in this review, entails this term, so the claim is true but less informative. |
| GO:0019900 kinase binding | IPI PMID:11432859 Cop, a caspase recruitment domain-containing protein and inh... | KEEP AS NON CORE | Summary: Binding to the CARD kinase RIP2/RICK and related CARD regulators. Reason: CASP1 binds the CARD-containing kinase RIP2/RICK/CARDIAK, which oligomerizes the zymogen. This is a real, specific interaction but is a regulatory input, not the core catalytic function. Supporting Evidence: PMID:11432859 binding of the caspase-1 prodomain to a caspase recruitment domain (CARD)-containing serine/threonine kinase known as RIP2/CARDIAK/RICK |
| GO:0019900 kinase binding | IPI PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | KEEP AS NON CORE | Summary: Binding to the CARD kinase RIP2/RICK and related CARD regulators. Reason: CASP1 binds the CARD-containing kinase RIP2/RICK/CARDIAK, which oligomerizes the zymogen. This is a real, specific interaction but is a regulatory input, not the core catalytic function. Supporting Evidence: PMID:11432859 binding of the caspase-1 prodomain to a caspase recruitment domain (CARD)-containing serine/threonine kinase known as RIP2/CARDIAK/RICK |
| GO:0019900 kinase binding | IPI PMID:15383541 INCA, a novel human caspase recruitment domain protein that ... | KEEP AS NON CORE | Summary: Binding to the CARD kinase RIP2/RICK and related CARD regulators. Reason: CASP1 binds the CARD-containing kinase RIP2/RICK/CARDIAK, which oligomerizes the zymogen. This is a real, specific interaction but is a regulatory input, not the core catalytic function. Supporting Evidence: PMID:11432859 binding of the caspase-1 prodomain to a caspase recruitment domain (CARD)-containing serine/threonine kinase known as RIP2/CARDIAK/RICK |
| GO:0019955 cytokine binding | IPI PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | KEEP AS NON CORE | Summary: Binding of the pro-IL-18 cytokine precursor substrate. Reason: A pro-IL-18 splice variant resistant to cleavage still binds caspase-1, documenting cytokine (precursor) binding. This is substrate engagement rather than a standalone core function; the core is the maturation it enables. Supporting Evidence: PMID:15326478 although it was capable to bind caspase-1 |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Response to lipopolysaccharide (IEA). Reason: CASP1-dependent IL-1beta secretion is a classic LPS-stimulated response; caspase-1 acts in the LPS-triggered inflammasome pathway. Non-core relative to the enzymatic function. Supporting Evidence: PMID:11536016 lipopolysaccharide-induced secretion of interleukin-1beta which is a well-known consequence of caspase-1 activation |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:11432859 Cop, a caspase recruitment domain-containing protein and inh... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:15326478 A novel isoform of pro-interleukin-18 expressed in ovarian t... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:16037825 Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, v... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:7642516 Cleavage of poly(ADP-ribose) polymerase by interleukin-1 bet... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000117 | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IMP PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | IMP PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032731 positive regulation of interleukin-1 beta production | NAS PMID:21918512 The NLRC4 inflammasome receptors for bacterial flagellin and... | ACCEPT | Summary: Core: positive regulation of IL-1beta production by maturing the active cytokine. Reason: CASP1 performs the proteolytic step that releases bioactive IL-1beta; loss of caspase-1 activity abolishes IL-1beta secretion. CASP1 does the work of this process (it is the maturation enzyme), so it participates rather than merely being required. Supporting Evidence: PMID:16037825 caspase-1 activation and interleukin-1beta processing |
| GO:0032741 positive regulation of interleukin-18 production | IDA PMID:15326478 A novel isoform of pro-interleukin-18 expressed in ovarian t... | ACCEPT | Summary: Core: positive regulation of IL-18 production by maturing the active cytokine. Reason: CASP1 cleaves pro-IL-18 at Asp36-Tyr37 to the bioactive 18 kDa form; it executes the maturation step of IL-18 production. Supporting Evidence: PMID:9334240 cleaves prohIL-18 at the Asp36-Tyr37 site to generate the mature hIL-18 |
| GO:0032991 protein-containing complex | IDA PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | ACCEPT | Summary: Member of a protein-containing complex (the inflammasome); a general parent of the specific inflammasome-complex terms. Reason: The specific complex terms (canonical, NLRP1/NLRP3/IPAF/AIM2 inflammasome) are the informative statements; this generic parent is correct and retained as background. Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 |
| GO:0032991 protein-containing complex | IMP PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | ACCEPT | Summary: Member of a protein-containing complex (the inflammasome); a general parent of the specific inflammasome-complex terms. Reason: The specific complex terms (canonical, NLRP1/NLRP3/IPAF/AIM2 inflammasome) are the informative statements; this generic parent is correct and retained as background. Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 |
| GO:0032991 protein-containing complex | IMP PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: Member of a protein-containing complex (the inflammasome); a general parent of the specific inflammasome-complex terms. Reason: The specific complex terms (canonical, NLRP1/NLRP3/IPAF/AIM2 inflammasome) are the informative statements; this generic parent is correct and retained as background. Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 |
| GO:0032991 protein-containing complex | IMP PMID:15383541 INCA, a novel human caspase recruitment domain protein that ... | ACCEPT | Summary: Member of a protein-containing complex (the inflammasome); a general parent of the specific inflammasome-complex terms. Reason: The specific complex terms (canonical, NLRP1/NLRP3/IPAF/AIM2 inflammasome) are the informative statements; this generic parent is correct and retained as background. Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 |
| GO:0042742 defense response to bacterium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Defense response to bacterium. Reason: Inflammasome/caspase-1-driven IL-1beta maturation and pyroptosis contribute to antibacterial defense. Supported by ISS and consistent with the bacterial-inflammasome literature; non-core relative to the enzymatic function. Supporting Evidence: PMID:18511561 Bacillus anthracis infection induces IL-1beta secretion in a manner that depended on caspase-1 and NOD2 |
| GO:0042802 identical protein binding | IMP PMID:11432859 Cop, a caspase recruitment domain-containing protein and inh... | ACCEPT | Summary: CASP1 self-associates: the active enzyme is a p20/p10 heterotetramer and the CARD forms homotypic filaments. Reason: Identical protein binding is well supported. The holoenzyme is a homodimer of two p20/p10 catalytic domains, and the isolated caspase-1 CARD polymerizes into a filament whose structure was solved by cryo-EM. This is real homo-oligomerization, not generic protein binding. Supporting Evidence: PMID:27043298 we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation |
| GO:0042802 identical protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: CASP1 self-associates: the active enzyme is a p20/p10 heterotetramer and the CARD forms homotypic filaments. Reason: Identical protein binding is well supported. The holoenzyme is a homodimer of two p20/p10 catalytic domains, and the isolated caspase-1 CARD polymerizes into a filament whose structure was solved by cryo-EM. This is real homo-oligomerization, not generic protein binding. Supporting Evidence: PMID:27043298 we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation |
| GO:0042802 identical protein binding | IPI PMID:27043298 Molecular basis of caspase-1 polymerization and its inhibiti... | ACCEPT | Summary: CASP1 self-associates: the active enzyme is a p20/p10 heterotetramer and the CARD forms homotypic filaments. Reason: Identical protein binding is well supported. The holoenzyme is a homodimer of two p20/p10 catalytic domains, and the isolated caspase-1 CARD polymerizes into a filament whose structure was solved by cryo-EM. This is real homo-oligomerization, not generic protein binding. Supporting Evidence: PMID:27043298 we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Regulation of apoptotic process (IEA). Reason: Consistent with the apoptosis-related activity of CASP1/ICE in overexpression and disease-model settings. Non-core relative to inflammatory cytokine maturation. Supporting Evidence: PMID:10799503 Pro-C1 acts to enhance Fas-mediated apoptosis |
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of apoptotic process (IBA). Reason: Phylogenetically the inflammatory caspases carry pro-apoptotic/cell-death regulation; for CASP1 this is secondary to its inflammatory cytokine and pyroptotic roles. Supporting Evidence: PMID:10799503 Expression of recombinant Pro-C1 in HeLa cells enhanced apoptosis mediated by Fas |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | KEEP AS NON CORE | Summary: Positive regulation of canonical NF-kappaB signalling (context-specific). Reason: Procaspase-1 was identified as an NF-kappaB activator in a large screen, and it regulates TLR2/4-NF-kappaB signalling by cleaving the adaptor Mal/TIRAP. A real but context-dependent and indirect role, not the core function. Supporting Evidence: PMID:15383541 Unlike COP/Pseudo-ICE and procaspase-1, INCA does not interact with RIP2 and does not induce NF-kappaB activation |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:15383541 INCA, a novel human caspase recruitment domain protein that ... | KEEP AS NON CORE | Summary: Positive regulation of canonical NF-kappaB signalling (context-specific). Reason: Procaspase-1 was identified as an NF-kappaB activator in a large screen, and it regulates TLR2/4-NF-kappaB signalling by cleaving the adaptor Mal/TIRAP. A real but context-dependent and indirect role, not the core function. Supporting Evidence: PMID:15383541 Unlike COP/Pseudo-ICE and procaspase-1, INCA does not interact with RIP2 and does not induce NF-kappaB activation |
| GO:0046456 icosanoid biosynthetic process | NAS PMID:22902502 Rapid induction of inflammatory lipid mediators by the infla... | MARK AS OVER ANNOTATED | Summary: Icosanoid biosynthetic process: a downstream physiological consequence, not a CASP1 enzymatic step. Reason: NLRC4/caspase-1 activation triggers an in vivo "eicosanoid storm", but CASP1 does not catalyze eicosanoid synthesis; the lipid mediators are produced downstream by lipid-metabolizing enzymes. By the participation test CASP1 does not do the work of this process. Supporting Evidence: PMID:22902502 inflammasome activation results, within minutes, in an 'eicosanoid storm' |
| GO:0050700 CARD domain binding | IPI PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: CARD-domain binding is the mechanism by which CASP1 is recruited into inflammasomes and regulated by CARD-only proteins. Reason: CASP1 engages its activators and regulators through homotypic CARD-CARD contacts: COP/CARD16 binds the caspase-1 prodomain, and CARD8 interacts with the CARD. This is an informative molecular function (not bare protein binding). Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 PMID:16920334 the known interaction of Cop and caspase-1 |
| GO:0050700 CARD domain binding | IPI PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | ACCEPT | Summary: CARD-domain binding is the mechanism by which CASP1 is recruited into inflammasomes and regulated by CARD-only proteins. Reason: CASP1 engages its activators and regulators through homotypic CARD-CARD contacts: COP/CARD16 binds the caspase-1 prodomain, and CARD8 interacts with the CARD. This is an informative molecular function (not bare protein binding). Supporting Evidence: PMID:11821383 CARD-8 interacts physically with caspase-1 PMID:16920334 the known interaction of Cop and caspase-1 |
| GO:0050727 regulation of inflammatory response | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of inflammatory response (IBA plus direct annotations). Reason: CASP1 is a central regulator of inflammation through cytokine maturation and pyroptosis. Correct at this level; the positive-regulation child is more specific. Supporting Evidence: PMID:32553275 essential steps in initiating pyroptosis after inflammasome activation |
| GO:0050727 regulation of inflammatory response | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Regulation of inflammatory response (IBA plus direct annotations). Reason: CASP1 is a central regulator of inflammation through cytokine maturation and pyroptosis. Correct at this level; the positive-regulation child is more specific. Supporting Evidence: PMID:32553275 essential steps in initiating pyroptosis after inflammasome activation |
| GO:0050727 regulation of inflammatory response | IDA PMID:32553275 Caspase-1 Engages Full-Length Gasdermin D through Two Distin... | ACCEPT | Summary: Regulation of inflammatory response (IBA plus direct annotations). Reason: CASP1 is a central regulator of inflammation through cytokine maturation and pyroptosis. Correct at this level; the positive-regulation child is more specific. Supporting Evidence: PMID:32553275 essential steps in initiating pyroptosis after inflammasome activation |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:12191486 The inflammasome: a molecular platform triggering activation... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:15326478 A novel isoform of pro-interleukin-18 expressed in ovarian t... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:32553275 Caspase-1 Engages Full-Length Gasdermin D through Two Distin... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | NAS PMID:21918512 The NLRC4 inflammasome receptors for bacterial flagellin and... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | NAS PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0050729 positive regulation of inflammatory response | NAS PMID:29255148 Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflamm... | ACCEPT | Summary: Positive regulation of inflammatory response. Reason: By maturing IL-1beta/IL-18 and executing pyroptosis, CASP1 positively drives the inflammatory response; supported by multiple direct annotations. Supporting Evidence: PMID:12191486 the inflammasome constitutes an important arm of the innate immunity |
| GO:0051604 protein maturation | IDA PMID:15326478 A novel isoform of pro-interleukin-18 expressed in ovarian t... | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | IDA PMID:32553275 Caspase-1 Engages Full-Length Gasdermin D through Two Distin... | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | IDA PMID:9334240 Involvement of caspase-1 and caspase-3 in the production and... | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | IEA GO_REF:0000117 | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051604 protein maturation | ISS GO_REF:0000024 | ACCEPT | Summary: Core process: protein maturation (cytokine precursor cleavage). Reason: CASP1 attains functional cytokines by proteolytic maturation of pro-IL-18 and pro-IL-1beta, and cleaves GSDMD to its active fragment. Multiple IDA annotations support this. Supporting Evidence: PMID:9334240 to generate the mature hIL-18 PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis |
| GO:0051607 defense response to virus | NAS PMID:28314590 Inflammasome Activation Triggers Caspase-1-Mediated Cleavage... | KEEP AS NON CORE | Summary: Defense response to virus (with a regulatory nuance). Reason: During DNA-virus infection caspase-1 cleaves cGAS and thereby dampens type-I IFN; inflammasome deficiency enhances antiviral resistance. CASP1 participates in the antiviral response but as a negative regulator of cGAS-STING, which the involved_in term does not capture precisely. Supporting Evidence: PMID:28314590 caspase-1 interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS), cleaving it and dampening cGAS-STING-mediated IFN production |
| GO:0061702 canonical inflammasome complex | IEA GO_REF:0000117 | ACCEPT | Summary: CASP1 is the effector of canonical (caspase-1-activating) inflammasomes. Reason: The canonical inflammasome is the caspase-1-activating platform assembled with ASC and a sensor. CASP1 is a defining component. Supported experimentally and by the NAIP-NLRC4 review. Supporting Evidence: PMID:16037825 assemble an inflammasome complex with ASC and procaspase-1 |
| GO:0061702 canonical inflammasome complex | IPI PMID:16037825 Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, v... | ACCEPT | Summary: CASP1 is the effector of canonical (caspase-1-activating) inflammasomes. Reason: The canonical inflammasome is the caspase-1-activating platform assembled with ASC and a sensor. CASP1 is a defining component. Supported experimentally and by the NAIP-NLRC4 review. Supporting Evidence: PMID:16037825 assemble an inflammasome complex with ASC and procaspase-1 |
| GO:0061702 canonical inflammasome complex | NAS PMID:25879286 The NAIP-NLRC4 inflammasome in innate immune detection of ba... | ACCEPT | Summary: CASP1 is the effector of canonical (caspase-1-activating) inflammasomes. Reason: The canonical inflammasome is the caspase-1-activating platform assembled with ASC and a sensor. CASP1 is a defining component. Supported experimentally and by the NAIP-NLRC4 review. Supporting Evidence: PMID:16037825 assemble an inflammasome complex with ASC and procaspase-1 |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000117 | ACCEPT | Summary: Involved in protein-containing complex assembly (inflammasome assembly). Reason: CASP1 is recruited and clustered during inflammasome assembly; the IEA parent is consistent with the experimental inflammasome-assembly literature. Supporting Evidence: PMID:24630722 ASC thus nucleates CARD filaments of caspase-1 |
| GO:0070269 pyroptotic inflammatory response | IDA PMID:32109412 Structural Mechanism for GSDMD Targeting by Autoprocessed Ca... | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0070269 pyroptotic inflammatory response | IDA PMID:32553275 Caspase-1 Engages Full-Length Gasdermin D through Two Distin... | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:26121197 Inflammasomes: mechanism of action, role in disease, and the... | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:26611636 Gasdermin D is an executor of pyroptosis and required for in... | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:29196474 Inflammasome activation and assembly at a glance. | ACCEPT | Summary: Core: pyroptotic inflammatory response via GSDMD cleavage. Reason: CASP1 cleaves GSDMD in its interdomain linker, releasing the pore-forming N-terminal fragment that executes pyroptosis. CASP1 performs the activating cleavage, so it participates in pyroptosis. Supporting Evidence: PMID:32553275 The recognition and cleavage of gasdermin D (GSDMD) by inflammatory caspases-1, 4, 5, and 11 are essential steps in initiating pyroptosis after inflammasome activation |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:22464733 Inflammasome-activated caspase 7 cleaves PARP1 to enhance th... | KEEP AS NON CORE | Summary: Cellular response to lipopolysaccharide. Reason: After LPS stimulation caspase-1 activates caspase-7 and drives IL-1beta processing; CASP1 acts within the cellular LPS response. Supported by IDA and IMP. Supporting Evidence: PMID:22464733 after LPS stimulation, caspase 7 is activated by caspase 1 |
| GO:0071222 cellular response to lipopolysaccharide | IMP PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | KEEP AS NON CORE | Summary: Cellular response to lipopolysaccharide. Reason: After LPS stimulation caspase-1 activates caspase-7 and drives IL-1beta processing; CASP1 acts within the cellular LPS response. Supported by IDA and IMP. Supporting Evidence: PMID:22464733 after LPS stimulation, caspase 7 is activated by caspase 1 |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | UNDECIDED | Summary: Cellular response to mechanical stimulus (IEP). Reason: The cached publication (PMID:19593445) is about BAD and prostate cancer growth and I cannot verify from it a caspase-1 mechanical-stimulus response. The full text may support the annotation; I defer rather than remove an experimental annotation whose supporting text I cannot read. |
| GO:0071346 cellular response to type II interferon | IMP PMID:11536016 Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG,... | KEEP AS NON CORE | Summary: Cellular response to type II interferon (IFN-gamma). Reason: IFN-gamma-induced IL-1beta secretion depends on caspase-1 activity (blocked by the CARD-only inhibitors). CASP1 acts within the IFN-gamma response; non-core. Supporting Evidence: PMID:11536016 interferon-gamma and lipopolysaccharide-induced secretion of interleukin-1beta which is a well-known consequence of caspase-1 activation |
| GO:0072557 IPAF inflammasome complex | IBA GO_REF:0000033 | ACCEPT | Summary: Component of the NLRC4/IPAF inflammasome. Reason: NLRC4/IPAF directly binds and activates procaspase-1 via CARD-CARD interaction; CASP1 is part of this complex. IBA and ISS are consistent with the direct-interaction literature. Supporting Evidence: PMID:11390368 Ipaf associates directly and specifically with the CARD domain of procaspase-1 through CARD-CARD interaction |
| GO:0072557 IPAF inflammasome complex | ISS GO_REF:0000024 | ACCEPT | Summary: Component of the NLRC4/IPAF inflammasome. Reason: NLRC4/IPAF directly binds and activates procaspase-1 via CARD-CARD interaction; CASP1 is part of this complex. IBA and ISS are consistent with the direct-interaction literature. Supporting Evidence: PMID:11390368 Ipaf associates directly and specifically with the CARD domain of procaspase-1 through CARD-CARD interaction |
| GO:0072558 NLRP1 inflammasome complex | IDA PMID:12191486 The inflammasome: a molecular platform triggering activation... | ACCEPT | Summary: Component of the NLRP1 inflammasome. Reason: The NLRP1 (NALP1) inflammasome was defined as comprising caspase-1, caspase-5, ASC and NALP1, and reconstituted from purified proteins. CASP1 membership is well established. Supporting Evidence: PMID:12191486 The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1 PMID:17349957 we have reconstituted the NALP1 inflammasome |
| GO:0072558 NLRP1 inflammasome complex | IPI PMID:17349957 Reconstituted NALP1 inflammasome reveals two-step mechanism ... | ACCEPT | Summary: Component of the NLRP1 inflammasome. Reason: The NLRP1 (NALP1) inflammasome was defined as comprising caspase-1, caspase-5, ASC and NALP1, and reconstituted from purified proteins. CASP1 membership is well established. Supporting Evidence: PMID:12191486 The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1 PMID:17349957 we have reconstituted the NALP1 inflammasome |
| GO:0072559 NLRP3 inflammasome complex | IBA GO_REF:0000033 | ACCEPT | Summary: Component of the NLRP3 inflammasome. Reason: NALP3/NLRP3 associates with ASC and caspase-1 to form a high-activity proIL-1beta-processing inflammasome. CASP1 is the effector of this complex. Supporting Evidence: PMID:15030775 NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity |
| GO:0072559 NLRP3 inflammasome complex | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: Component of the NLRP3 inflammasome. Reason: NALP3/NLRP3 associates with ASC and caspase-1 to form a high-activity proIL-1beta-processing inflammasome. CASP1 is the effector of this complex. Supporting Evidence: PMID:15030775 NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity |
| GO:0072559 NLRP3 inflammasome complex | IPI PMID:29255148 Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflamm... | ACCEPT | Summary: Component of the NLRP3 inflammasome. Reason: NALP3/NLRP3 associates with ASC and caspase-1 to form a high-activity proIL-1beta-processing inflammasome. CASP1 is the effector of this complex. Supporting Evidence: PMID:15030775 NALP2 and NALP3 associate with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), thereby forming an inflammasome with high proIL-1beta-processing activity |
| GO:0097169 AIM2 inflammasome complex | IBA GO_REF:0000033 | ACCEPT | Summary: Component of the AIM2 inflammasome. Reason: AIM2 senses cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. CASP1 is the effector protease of this complex; supported by IDA, IPI and the phylogenetic IBA. Supporting Evidence: PMID:19158676 inflammasome, which activates caspase-1 |
| GO:0097169 AIM2 inflammasome complex | IDA PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: Component of the AIM2 inflammasome. Reason: AIM2 senses cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. CASP1 is the effector protease of this complex; supported by IDA, IPI and the phylogenetic IBA. Supporting Evidence: PMID:19158676 inflammasome, which activates caspase-1 |
| GO:0097169 AIM2 inflammasome complex | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: Component of the AIM2 inflammasome. Reason: AIM2 senses cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. CASP1 is the effector protease of this complex; supported by IDA, IPI and the phylogenetic IBA. Supporting Evidence: PMID:19158676 inflammasome, which activates caspase-1 |
| GO:0097179 protease inhibitor complex | IMP PMID:11432859 Cop, a caspase recruitment domain-containing protein and inh... | KEEP AS NON CORE | Summary: Part of a protease-inhibitor (enzyme-inhibitor) complex with the CARD-only inhibitor COP. Reason: COP binds the caspase-1 prodomain and inhibits its oligomerization/activation; the caspase-1:COP pairing is an enzyme-inhibitor complex in which CASP1 is the inhibited protease. Real but peripheral to the core catalytic function. Supporting Evidence: PMID:11432859 COP inhibits caspase- 1-induced IL-1beta secretion |
| GO:0140447 cytokine precursor processing | IGI PMID:15882992 Nucleotide binding to CARD12 and its role in CARD12-mediated... | ACCEPT | Summary: Core process: maturation of cytokine precursors (pro-IL-1beta, pro-IL-18). Reason: CARD12/Ipaf-mediated caspase-1 activation drives proIL-1beta processing; cleavage of pro-IL-1beta and pro-IL-18 to their active cytokines is the central physiological role of CASP1. Supporting Evidence: PMID:15882992 the P-loop mutation greatly reduced caspase-1 activation-dependent proIL-1beta processing |
| GO:0140448 signaling receptor ligand precursor processing | IGI PMID:15882992 Nucleotide binding to CARD12 and its role in CARD12-mediated... | ACCEPT | Summary: Core process: processing of signaling-receptor ligand precursors (pro-IL-1beta/pro-IL-18) to their active, receptor-binding forms. Reason: IL-1beta and IL-18 are ligands for IL-1/IL-18 receptors; CASP1 cleavage converts the inactive precursors into the mature receptor-binding ligands. Same physiological event as cytokine precursor processing. Supporting Evidence: PMID:15882992 the P-loop mutation greatly reduced caspase-1 activation-dependent proIL-1beta processing PMID:9334240 caspase-1, which cleaves prohIL-18 at the Asp36-Tyr37 site to generate the mature hIL-18 |
| GO:0140970 AIM2 inflammasome complex assembly | IDA PMID:19158675 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activa... | ACCEPT | Summary: Involved in assembly of the AIM2 inflammasome. Reason: AIM2 nucleates the ASC-caspase-1 inflammasome upon dsDNA sensing; recruitment and clustering of caspase-1 is part of assembling this caspase-1-activating platform. Supporting Evidence: PMID:19158675 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IDA PMID:39333773 The human disease-associated gene ZNFX1 controls inflammatio... | ACCEPT | Summary: Positive regulation of NLRP3 inflammasome complex assembly via ZNFX1 cleavage. Reason: Upon NLRP3 activation, caspase-1 cleaves ZNFX1, establishing a feed-forward loop that promotes NLRP3 accumulation in the trans-Golgi and amplifies the cascade. CASP1 performs the cleavage that drives this amplification. Supporting Evidence: PMID:39333773 ZNFX1 is cleaved by caspase-1, establishing a feed-forward loop that promotes NLRP3 accumulation in the trans-Golgi network (TGN) and amplifies the activity of the downstream cascade |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IMP PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | UNDECIDED | Summary: Positive regulation of TNF-mediated signalling, inferred from a study of the inhibitor COP. Reason: The cached abstract describes COP as an inhibitor of Rip2/caspase-1/caspase-4-mediated cell death and of TNF-alpha-induced death, and does not by itself show CASP1 positively regulating TNF signalling. This is an experimental (IMP) annotation and only the abstract is cached, so the curator may have relied on full-text data not visible here; deferred rather than marked as over-annotated. Supporting Evidence: PMID:16920334 Cop's action to prevent TNF-alpha-induced cell death |
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Download this section (compressed HTML)Q: Beyond IL-1 beta, IL-18 and GSDMD, which caspase-1 substrates (e.g. cGAS, caspase-7, SPHK2, ZNFX1) are cleaved at physiological enzyme levels in vivo versus only on overexpression, and what is the biological weight of each?
Q: What distinguishes the ASC-dependent (NLRP3/AIM2) from the ASC-independent (NLRC4/CARD8) mode of caspase-1 activation in terms of cytokine-maturation versus pyroptosis output?
Q: Which of the catalytically inactive splice isoforms (delta, epsilon) act as endogenous dominant-negative regulators of caspase-1 in human cells, and under what conditions?
Experiment: Degradomics (N-terminomics / TAILS) in primary human macrophages with inflammasome activation, comparing CASP1-knockout and catalytically dead (C285A) reconstitution, to define the physiological caspase-1 substrate repertoire at endogenous enzyme levels.
Experiment: Separation-of-function reconstitution of CASP1 variants defective in GSDMD-exosite binding versus cytokine cleavage, to test independently the contributions of pyroptosis and IL-1/IL-18 maturation to host defense and autoinflammation.
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