PYCARD (ASC; also TMS1) is a small 195-residue cytosolic adaptor protein built from only two death-fold domains - an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD) joined by a flexible linker - with no catalytic or ligand-sensing module. It is the shared adaptor of ASC-dependent inflammasomes. On activation, a sensor (NLRP3, NLRP1, NLRP6, AIM2, IFI16 or pyrin/MEFV) nucleates polymerization of the ASC PYD into filaments; the clustered ASC CARDs then nucleate procaspase-1 CARD filaments, bringing procaspase-1 molecules into proximity for autoprocessing. These filaments condense into a single micrometre-scale perinuclear 'speck' (also called the pyroptosome) per cell. Active caspase-1 matures pro-interleukin-1 beta and pro-interleukin-18 and cleaves gasdermin D to execute pyroptosis. ASC thus supplies the connectivity and signal-amplification geometry of the inflammasome rather than any enzymatic step. In resting monocytes/macrophages a pool of ASC is nuclear and must redistribute to the cytosol for inflammasome function; the protein is otherwise cytosolic. Its activity is tuned by post-translational modification (K63 ubiquitination at K174, tyrosine phosphorylation) and by competing pyrin-domain-only proteins (POP1/2/3). Released ASC specks persist extracellularly and propagate inflammation. Beyond the inflammasome, ASC has context-dependent, inflammasome-independent activities reported in apoptosis (as a CARD/pyrin aggregating adaptor engaging caspase-8, caspase-9 and the p53-Bax mitochondrial pathway) and in NF-kB and MAPK signalling, where it can both activate and, via IKK suppression and DUSP10 regulation, dampen downstream cytokine output. PYCARD/ASC is central to the monogenic autoinflammatory syndromes driven by its sensor partners and to IL-1-driven inflammatory disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IDA PMID:23229815 Human respiratory syncytial virus viroporin SH: a viral reco... | KEEP AS NON CORE | Summary: ASC localizes to Golgi membrane/lipid rafts specifically during respiratory syncytial virus infection (HRSV SH viroporin), not as a constitutive location. Reason: This IDA reflects an infection-specific redistribution of ASC to Golgi lipid rafts seen with the HRSV small hydrophobic viroporin, not a resting ASC location. Retained as a non-core, context-specific localization; the core sites are cytosol and the assembled speck. Supporting Evidence: PMID:23229815 SH seems to accumulate within lipid rafts in the Golgi compartments |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic Golgi-membrane assignment from the UniProt subcellular-location mapping, reflecting the same infection-specific observation. Reason: Mirrors the IDA from PMID:23229815 via the SubCell mapping; infection-specific, non-core. |
| GO:0001773 myeloid dendritic cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic (ARBA) myeloid dendritic cell activation. Reason: ASC's reported role in dendritic-cell function is a secondary, inflammasome-independent effect, and much of the mouse DC/antigen-presentation phenotype attributed to ASC was later shown to be a Dock2 passenger-mutation artifact (PMID:22905357). An electronic activation term is an over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0001773 myeloid dendritic cell activation | IMP PMID:22732093 Central and overlapping role of Cathepsin B and inflammasome... | KEEP AS NON CORE | Summary: ASC knockdown impairs human dendritic-cell maturation and their capacity to stimulate T cells (RNAi in human monocyte-derived DCs). Reason: Experimental (IMP) support in human DCs via RNAi (PMID:22732093), independent of the mouse Dock2 confound. This is a genuine but secondary, non-core role of ASC distinct from its canonical inflammasome-adaptor function. Supporting Evidence: PMID:22732093 RNAi mediated inhibition of the inflammasome component ASC leads to marked inhibition of the capacity of lipopolysachharide (LPS)-matured DCs to stimulate antigen-specific T cells. |
| GO:0002020 protease binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic protease-binding transfer from the rat ortholog. Reason: The same term is marked as an over-annotation on the physical-interaction row of this review, and the claim is the same here. The rat source annotations record real interactions of ASC with caspases, but ASC is the adaptor that recruits and activates procaspase-1, which the cysteine-type endopeptidase activator activity annotation states more precisely. Rows that share a term are judged alike, so the transferred row is marked rather than removed. |
| GO:0002020 protease binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: Protease-binding from a PML-focused interactome screen. Reason: This 'protease binding' derives from a single PML-centred proteomic interaction dataset and names enteropeptidase (an intestinal serine protease unrelated to ASC biology). This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0002218 activation of innate immune response | IBA GO_REF:0000033 | ACCEPT | Summary: ASC-dependent inflammasomes activate caspase-1 and the innate immune response; phylogenetically inferred. Reason: IBA from the inflammasome-family node. ASC is the shared adaptor that activates caspase-1 across multiple inflammasomes, so participation in activation of the innate immune response is correct. Supporting Evidence: PMID:24630722 The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain (PYD) interactions between sensors and ASC and through caspase activation and recruitment domain (CARD) interactions between ASC and caspase-1. |
| GO:0002218 activation of innate immune response | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of activation of innate immune response from mouse ortholog. Reason: Consistent with the experimentally supported adaptor role in caspase-1 activation; electronic but correct. Supporting Evidence: PMID:29196474 The inflammasome platform leads to activation of caspase-1 through proximity-induced self-cleavage |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:21918512 The NLRC4 inflammasome receptors for bacterial flagellin and... | ACCEPT | Summary: ASC functions downstream of pattern-recognition receptors (NLRs/ALRs) as the adaptor transmitting the signal to caspase-1. Reason: ASC is recruited by pattern-recognition-receptor sensors and relays their signal; involvement in PRR signaling is well supported. Multiple NAS review citations support the same claim. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:22258606 Inflammasomes in health and disease. | ACCEPT | Summary: ASC functions downstream of pattern-recognition receptors (NLRs/ALRs) as the adaptor transmitting the signal to caspase-1. Reason: ASC is recruited by pattern-recognition-receptor sensors and relays their signal; involvement in PRR signaling is well supported. Multiple NAS review citations support the same claim. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:29196474 Inflammasome activation and assembly at a glance. | ACCEPT | Summary: ASC functions downstream of pattern-recognition receptors (NLRs/ALRs) as the adaptor transmitting the signal to caspase-1. Reason: ASC is recruited by pattern-recognition-receptor sensors and relays their signal; involvement in PRR signaling is well supported. Multiple NAS review citations support the same claim. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| GO:0002221 pattern recognition receptor signaling pathway | NAS PMID:29247998 The AIM2 inflammasome: Sensor of pathogens and cellular pert... | ACCEPT | Summary: ASC functions downstream of pattern-recognition receptors (NLRs/ALRs) as the adaptor transmitting the signal to caspase-1. Reason: ASC is recruited by pattern-recognition-receptor sensors and relays their signal; involvement in PRR signaling is well supported. Multiple NAS review citations support the same claim. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| GO:0002230 positive regulation of defense response to virus by host | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic (mouse) positive regulation of host defense response to virus. Reason: ASC participates in antiviral inflammasomes (AIM2, IFI16, NLRP6), so an antiviral-defense role is plausible but secondary and electronically transferred. Supporting Evidence: PMID:21575908 interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome |
| GO:0002277 myeloid dendritic cell activation involved in immune response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) DC activation in immune response. Reason: Secondary DC role; the mouse antigen-presentation phenotype is confounded by the Dock2 passenger mutation (PMID:22905357). Over-annotation by electronic/ortholog transfer. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0002277 myeloid dendritic cell activation involved in immune response | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse ortholog) DC activation in immune response. Reason: Same secondary DC role, transferred by sequence similarity from mouse; Dock2 confound applies. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0002588 positive regulation of antigen processing and presentation of peptide antigen via MHC class II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) positive regulation of MHC-II antigen presentation. Reason: The mouse antigen-presentation defect attributed to ASC was shown to arise from a Dock2 passenger mutation present in only some ASC-knockout lines (PMID:22905357), not from loss of ASC. Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0002588 positive regulation of antigen processing and presentation of peptide antigen via MHC class II | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) positive regulation of MHC-II antigen presentation. Reason: Same Dock2-confounded antigen-presentation phenotype transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0002821 positive regulation of adaptive immune response | IMP PMID:22732093 Central and overlapping role of Cathepsin B and inflammasome... | KEEP AS NON CORE | Summary: ASC knockdown in human DCs reduces their capacity to drive antigen-specific T-cell responses. Reason: Human RNAi evidence (PMID:22732093) for a secondary, inflammasome-independent role in shaping adaptive immunity; non-core relative to the inflammasome-adaptor function. Supporting Evidence: PMID:22732093 RNAi mediated inhibition of the inflammasome component ASC leads to marked inhibition of the capacity of lipopolysachharide (LPS)-matured DCs to stimulate antigen-specific T cells. |
| GO:0005138 interleukin-6 receptor binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: Interleukin-6 receptor binding from the PML interactome screen (partner gp130/IL6ST). Reason: A cytosolic inflammasome adaptor has no credible IL-6-receptor-binding function. This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0005515 protein binding | IPI PMID:11498534 Interaction between pyrin and the apoptotic speck protein (A... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:11786556 PYPAF1, a PYRIN-containing Apaf1-like protein that assembles... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:12019269 PYPAF7, a novel PYRIN-containing Apaf1-like protein that reg... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:12656673 The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:15020601 Cryopyrin-induced interleukin 1beta secretion in monocytic c... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:17178784 Cellular pyrin domain-only protein 2 is a candidate regulato... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:17418785 Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activati... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:17964261 Pyrin activates the ASC pyroptosome in response to engagemen... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:19158675 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activa... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:19158675 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activa... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:22286270 Activation of autophagy by inflammatory signals limits IL-1Ξ²... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24237704 Human cytomegalovirus tegument protein pUL83 inhibits IFI16-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24531343 The PYRIN domain-only protein POP3 inhibits ALR inflammasome... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25006247 Identification of multifaceted binding modes for pyrin and A... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25277106 Overexpressed NLRC3 acts as an anti-inflammatory cytosolic p... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25402006 In silico prediction of physical protein interactions and ch... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25605870 Syk is involved in NLRP3 inflammasome-mediated caspase-1 act... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:25605870 Syk is involved in NLRP3 inflammasome-mediated caspase-1 act... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:28229991 A Novel Mutation in the Pyrin Domain of the NOD-like Recepto... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:28636595 Nlrp9b inflammasome restricts rotavirus infection in intesti... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:31421660 Expression of a PYCARD/ASC variant lacking exon 2 in Japanes... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:31421660 Expression of a PYCARD/ASC variant lacking exon 2 in Japanes... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:34341353 SARS-CoV-2 N protein promotes NLRP3 inflammasome activation ... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:34589402 Lonicerin targets EZH2 to alleviate ulcerative colitis by au... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:34589402 Lonicerin targets EZH2 to alleviate ulcerative colitis by au... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:38593810 Truncating NFKB1 variants cause combined NLRP3 inflammasome ... | REMOVE | Summary: Bare 'protein binding' from an individual two-hybrid or co-IP interaction study. Reason: Uninformative as a molecular function. Several underlying interactions are biologically important and are captured by specific terms elsewhere in this review (NLRP3/pyrin/AIM2 recruitment via GO:0032090 Pyrin domain binding; procaspase-1 activation via GO:0140608; self-association via GO:0042802). The bare term adds no functional information. Removal does not imply the interaction is false. |
| GO:0005523 tropomyosin binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: Tropomyosin binding from the PML interactome screen (partner TPM4). Reason: Not a credible ASC function. This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic extracellular-region assignment (mouse/ARBA). Reason: Oligomeric ASC specks are released into the extracellular space and perpetuate inflammation (ASC specks detected in serum of CAPS patients, PMID:24952504), so an extracellular location is real but secondary. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Extracellular region via Reactome neutrophil-degranulation pathway. Reason: Reactome places ASC in granule-secretion pathways; this is pathway membership rather than a characteristic ASC localization and over-states an extracellular role. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798751 | KEEP AS NON CORE | Summary: Extracellular region via Reactome neutrophil-degranulation pathway. Reason: Reactome degranulation-pathway membership, not a primary ASC localization. |
| GO:0005634 nucleus | EXP PMID:19234215 Activation of inflammasomes requires intracellular redistrib... | KEEP AS NON CORE | Summary: ASC is present in the nucleus of resting monocytes/macrophages and redistributes to the cytosol upon stimulation. Reason: Experimental (PMID:19234215): resting ASC is nuclear and must relocate to the cytosol for inflammasome function. The functional site is the cytosolic speck, so nuclear localization is retained as non-core. Supporting Evidence: PMID:19234215 ASC localized primarily to the nucleus in resting human monocytes/macrophages |
| GO:0005634 nucleus | EXP PMID:25847972 MAVS Promotes Inflammasome Activation by Targeting ASC for K... | KEEP AS NON CORE | Summary: ASC detected in the nucleus (MAVS/TRAF3 ubiquitination study). Reason: Supports a nuclear pool of ASC (PMID:25847972 reports nuclear/cytosolic ASC regulation); non-core relative to the cytosolic inflammasome. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic assignment of nuclear activity. Reason: ASC's active signalling site is the cytosolic/perinuclear speck, not the nucleus; nuclear localization is a resting-state pool. Retained as non-core rather than as the site of activity. Supporting Evidence: PMID:19234215 cytosolic localization of ASC is essential for inflammasome function |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic nucleus assignment. Reason: Consistent with the experimental resting nuclear pool; non-core. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS (mouse) nucleus assignment. Reason: Consistent with the resting nuclear pool; non-core. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasm from immunofluorescence (HPA). Reason: Consistent with the resting nuclear pool of ASC; non-core relative to the cytosolic speck. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleolus from immunofluorescence (HPA). Reason: A nucleolar subpool may exist but is not functionally characterized for ASC; retained as non-core. |
| GO:0005730 nucleolus | NAS PMID:28263976 NLRP1 promotes tumor growth by enhancing inflammasome activa... | MARK AS OVER ANNOTATED | Summary: Nucleolus (NAS). Reason: The cited paper (PMID:28263976) reports nucleolar localization of NLRP1, not of ASC/PYCARD; applying it to ASC is an over-annotation. Supporting Evidence: PMID:28263976 NLRP1 is primarily in the nucleolus of THP-1 cells |
| GO:0005737 cytoplasm | EXP PMID:11103777 Activation of a caspase-9-mediated apoptotic pathway by subc... | ACCEPT | Summary: ASC is a cytoplasmic protein that forms a perinuclear aggregate (speck) during apoptosis/activation. Reason: Core localization. Experimental cytoplasmic localization with speck formation (PMID:11103777). Supporting Evidence: PMID:11103777 TMS1-induced apoptosis proceeds through a CARD-dependent aggregation step followed by activation of a caspase-9-mediated pathway |
| GO:0005737 cytoplasm | EXP PMID:19234215 Activation of inflammasomes requires intracellular redistrib... | ACCEPT | Summary: Cytoplasmic localization of ASC with stimulus-induced redistribution. Reason: Core cytoplasmic localization (PMID:19234215). Supporting Evidence: PMID:19234215 ASC localized primarily to the nucleus in resting human monocytes/macrophages |
| GO:0005737 cytoplasm | EXP PMID:25847972 MAVS Promotes Inflammasome Activation by Targeting ASC for K... | ACCEPT | Summary: Cytoplasmic ASC (MAVS/TRAF3 study). Reason: Core cytoplasmic localization where the speck assembles. |
| GO:0005737 cytoplasm | IDA PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | ACCEPT | Summary: ASC in cytoplasm (p53-Bax apoptosis study). Reason: Core cytoplasmic localization. |
| GO:0005737 cytoplasm | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: Cytoplasmic ASC in the NALP3 inflammasome study. Reason: Core cytoplasmic localization (PMID:15030775). 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:0005737 cytoplasm | IDA PMID:19158679 An orthogonal proteomic-genomic screen identifies AIM2 as a ... | ACCEPT | Summary: Cytoplasmic ASC in the AIM2 DNA-sensor study. Reason: Core cytoplasmic localization. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic cytoplasm assignment. Reason: Consistent with the core cytoplasmic localization. |
| GO:0005737 cytoplasm | NAS PMID:12019269 PYPAF7, a novel PYRIN-containing Apaf1-like protein that reg... | ACCEPT | Summary: Cytoplasm (NAS, PYPAF7 study). Reason: ASC recruits PYPAF-family sensors to cytoplasmic loci; consistent with core cytoplasmic localization. Supporting Evidence: PMID:11786556 When expressed in cells, ASC recruits PYPAF1 to distinct cytoplasmic loci and induces the activation of NF-kappaB. |
| GO:0005737 cytoplasm | NAS PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: Cytoplasm (NAS, AIM2 study). Reason: Consistent with core cytoplasmic localization. Supporting Evidence: PMID:19158676 interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1 |
| GO:0005737 cytoplasm | NAS PMID:24803432 Inflammasome activation causes dual recruitment of NLRC4 and... | ACCEPT | Summary: Cytoplasm (NAS, Salmonella NLRC4/NLRP3 study). Reason: Consistent with core cytoplasmic localization; ASC forms the outer ring of the macromolecular inflammasome. Supporting Evidence: PMID:24803432 an outer ring of apoptosis-associated speck-like protein containing a caspase activation and recruitment domain and an inner ring of NLRs |
| GO:0005737 cytoplasm | NAS PMID:28263976 NLRP1 promotes tumor growth by enhancing inflammasome activa... | ACCEPT | Summary: Cytoplasm (NAS, melanoma NLRP1 study). Reason: Consistent with core cytoplasmic localization. Supporting Evidence: PMID:11103777 the redistribution of TMS1 from the cytoplasm to perinuclear spherical structures |
| GO:0005739 mitochondrion | EXP PMID:21124315 A role for mitochondria in NLRP3 inflammasome activation. | KEEP AS NON CORE | Summary: ASC/NLRP3 redistribute to the perinuclear ER-mitochondria cluster upon inflammasome activation. Reason: On activation ASC co-localizes with mitochondria/ER (PMID:21124315); an activation-dependent, non-core localization. ORGANELLES check (2026-11-03): the cached copy is abstract-only, and the abstract describes redistribution to perinuclear clusters where ER and mitochondria co-localize, an imaging readout that cannot separate the mitochondrion from ER contacts (MAM); the curator's EXP row is not overruled. This is transient, stimulus-dependent recruitment of a soluble adaptor, not an outer-membrane location (TRAF3/BRAF precedent): ASC has no presequence or TM segment and is absent from MitoCarta3.0, so the gene stays at the root. Supporting Evidence: PMID:21124315 on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters |
| GO:0005739 mitochondrion | IDA PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC at mitochondria in the p53-Bax apoptosis pathway. Reason: Mitochondrial ASC in the overexpression Bax-apoptosis context (PMID:14730312); non-core. ORGANELLES check (2026-11-03): the abstract (cache abstract-only) reports that ectopically expressed ASC colocalized with Bax at mitochondria, i.e. organelle-level co-staining of an overexpressed protein recruited with a partner; no sub-mitochondrial assay, so the row stays at the root as non-core. The quote now cites the sentence about ASC's own location rather than Bax translocation. Supporting Evidence: PMID:14730312 When ectopically expressed, ASC interacted directly with Bax, colocalized with Bax to the mitochondria PMID:14730312 ASC is required to translocate Bax to the mitochondria |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic mitochondrion assignment. Reason: Consistent with activation-dependent mitochondrial redistribution; non-core. ORGANELLES check (2026-11-03): SL-0173 maps UniProt's curated "Mitochondrion" location, which is tagged ECO:0000269 to PMID:14730312 and PMID:21124315, the two direct rows above, so the IEA adds no independent line but its organelle claim holds as far as those rows do. Transient recruitment, not a sub-compartment; stays at the root. |
| GO:0005783 endoplasmic reticulum | EXP PMID:21124315 A role for mitochondria in NLRP3 inflammasome activation. | KEEP AS NON CORE | Summary: ASC redistributes to perinuclear ER and mitochondria clusters upon NLRP3 inflammasome activation. Reason: Activation-dependent ER localization (PMID:21124315); non-core. ORGANELLES check (2026-11-05): the cached copy is abstract-only, and the abstract reports that on NLRP3 activation ASC co-localizes with perinuclear ER and mitochondria clusters, an imaging readout with no ER-specific marker or fractionation that cannot separate the ER from ER-mitochondria contacts; the curator's EXP row is not overruled. ASC is a soluble cytosolic PYD-CARD adaptor with no signal peptide, TM segment or retention motif, so this is a recruited pool on the cytosolic face that stays at the root (A1CF, BRSK2 precedent), consistent with the mitochondrion rows (batch 4, 2026-11-03). It is non-core because the adaptor's activity, speck nucleation and caspase-1 recruitment, is shown in the cytosol, not specifically at the ER; no ER sub-compartment or MAM row is added. Supporting Evidence: PMID:21124315 on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic ER assignment from the UniProt subcellular-location keyword. Reason: Consistent with activation-dependent ER redistribution; non-core. ORGANELLES check (2026-11-05): SL-0095 maps UniProt's "Endoplasmic reticulum" line, which is tagged ECO:0000269 to PMID:21124315 alone, the EXP row above, so the IEA adds no independent line; its organelle claim holds as far as that row does. A soluble adaptor recruited to the ER surface on activation, so it stays at the root with no membrane or lumen row. Supporting Evidence: file:human/PYCARD/PYCARD-uniprot.txt Upon NLRP3 inflammasome activation redistributes to the perinuclear space localizing to endoplasmic reticulum and mitochondria |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: ASC is a cytosolic adaptor (immunofluorescence). Reason: Core cytosolic localization where ASC nucleates into the speck. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic (mouse) cytosol. Reason: Core cytosolic localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660662 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660663 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844610 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-844612 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-877361 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9685281 | ACCEPT | Summary: Cytosolic localization via Reactome inflammasome pathways. Reason: Core cytosolic localization; Reactome places ASC in cytosolic inflammasome assembly. |
| GO:0005874 microtubule | NAS PMID:27911804 Familial Mediterranean fever mutations lift the obligatory r... | KEEP AS NON CORE | Summary: Microtubule association during pyrin-inflammasome ASC speck assembly. Reason: Microtubules relay signals for ASC speck nucleation (PMID:27911804); ASC transits/assembles in a microtubule-dependent manner rather than being a stable microtubule-resident protein. Non-core. Supporting Evidence: PMID:27911804 FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks) |
| GO:0006915 apoptotic process | TAS PMID:10567338 ASC, a novel 22-kDa protein, aggregates during apoptosis of ... | KEEP AS NON CORE | Summary: ASC was originally identified by its aggregation during drug-induced apoptosis. Reason: ASC participates in apoptosis in overexpression/knockdown systems (PMID:10567338); a secondary, non-core activity relative to its inflammasome role. Supporting Evidence: PMID:10567338 one mAb recognized a 22-kDa protein that exhibited intriguing behavior by forming an aggregate and appearing as a speck during apoptosis induced by retinoic acid and other anti-tumor drugs |
| GO:0006954 inflammatory response | IBA GO_REF:0000033 | ACCEPT | Summary: ASC is a central mediator of the inflammatory response through inflammasome assembly. Reason: IBA; ASC is the shared inflammasome adaptor driving the inflammatory response. Supporting Evidence: PMID:24630722 The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain (PYD) interactions between sensors and ASC and through caspase activation and recruitment domain (CARD) interactions between ASC and caspase-1. |
| GO:0006954 inflammatory response | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic (InterPro) inflammatory response. Reason: Consistent with ASC's core inflammatory role. |
| GO:0007165 signal transduction | NAS PMID:12019269 PYPAF7, a novel PYRIN-containing Apaf1-like protein that reg... | MARK AS OVER ANNOTATED | Summary: Generic signal transduction. Reason: Far too general; ASC's signalling role is captured specifically by PRR-signaling and inflammasome-assembly terms. Over-annotation. |
| GO:0007231 osmosensory signaling pathway | NAS PMID:22981536 Cell volume regulation modulates NLRP3 inflammasome activati... | MARK AS OVER ANNOTATED | Summary: Osmosensory signaling (cell-volume/NLRP3 study). Reason: The cited work (PMID:22981536) shows the NLRP3 sensor responds to cell swelling; ASC is the downstream adaptor and is not itself an osmosensor. Over-annotation for ASC. Supporting Evidence: PMID:22981536 the basic mechanisms of cell swelling and regulatory volume decrease (RVD) are sensed via the NLRP3 inflammasome |
| GO:0008385 IkappaB kinase complex | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC co-localizes with and acts upon the IKK complex to modulate NF-kB. Reason: ASC modulates NF-kB by acting on the IKK complex (PMID:12486103, colocalizes_with). ASC is not a stoichiometric subunit of the IKK complex, so this is retained as a non-core regulatory association rather than complex membership. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0008385 IkappaB kinase complex | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Electronic (ARBA) IkappaB kinase complex membership. Reason: The same term is kept on a direct-assay row, which records that ASC colocalizes with the IKK complex, and is marked as an over-annotation on the author-statement row that makes ASC part of the complex. This electronic row also asserts membership; ASC associates with and acts on the IKK complex but is not one of its subunits, so the membership claim over-states a real association. It is marked like the author-statement row rather than removed. Supporting Evidence: PMID:12486103 ASC modulates diverse NF-kappaB induction pathways by acting upon the IKK complex |
| GO:0008385 IkappaB kinase complex | TAS PMID:12656673 The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-... | MARK AS OVER ANNOTATED | Summary: IkappaB kinase complex (TAS, POP1 study). Reason: ASC regulates IKK/NF-kB signalling but is not a component of the IKK complex; part_of over-states the relationship. Supporting Evidence: PMID:12486103 ASC modulates diverse NF-kappaB induction pathways by acting upon the IKK complex |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic regulation of TNF-mediated signaling. Reason: ASC modulates TNF/NF-kB signalling (PMID:12486103); a secondary regulatory role. Supporting Evidence: PMID:12486103 ASC modulates diverse NF-kappaB induction pathways by acting upon the IKK complex |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | IMP PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC regulates TNF-mediated signaling (p53-Bax apoptosis study). Reason: Secondary regulatory role in TNF signalling (PMID:14730312); non-core. |
| GO:0017024 myosin I binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: Myosin I binding from the PML interactome screen (partner MYO1C). Reason: Not a credible ASC molecular function. This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0019899 enzyme binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: Enzyme binding (DNA ligase III) from the PML interactome screen. Reason: Bare, uninformative enzyme-binding from a single interactome dataset. This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:17349957 Reconstituted NALP1 inflammasome reveals two-step mechanism ... | MODIFY | Summary: ASC acts as the adaptor bridging inflammasome sensors to procaspase-1. Reason: ASC's molecular function is best described as signaling adaptor activity: it uses homotypic PYD and CARD interactions to link a sensor to caspase-1 within a signalling pathway. 'protein-macromolecule adaptor activity' is the parent; the more specific signaling adaptor activity (GO:0035591) captures the function and matches the partner NLRP3 review. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:17349957 Caspase-1 activation by NALP1 does not require but is enhanced by adaptor protein ASC. PMID:24630722 The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain (PYD) interactions between sensors and ASC and through caspase activation and recruitment domain (CARD) interactions between ASC and caspase-1. |
| GO:0030838 positive regulation of actin filament polymerization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) positive regulation of actin filament polymerization. Reason: This traces to the ASC-Dock2-Rac-actin phenotype (PMID:21892172), which the same authors later attributed to a Dock2 passenger mutation present in only some ASC-knockout lines (PMID:22905357). Not a safe direct ASC function. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0030838 positive regulation of actin filament polymerization | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) positive regulation of actin filament polymerization. Reason: Same Dock2-confounded actin phenotype transferred from mouse. Supporting Evidence: PMID:21892172 ASC, but not the cytoplasmic receptor NLRP3 or caspase-1, controlled the mRNA stability and expression of Dock2 |
| GO:0031647 regulation of protein stability | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) regulation of protein stability. Reason: Derived from the report that ASC controls Dock2 mRNA (not protein) stability (PMID:21892172), a phenotype later attributed to a Dock2 passenger mutation (PMID:22905357). Mislabelled and confounded. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0031647 regulation of protein stability | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) regulation of protein stability. Reason: Same mRNA-stability/Dock2 confound transferred from mouse. Supporting Evidence: PMID:21892172 ASC, but not the cytoplasmic receptor NLRP3 or caspase-1, controlled the mRNA stability and expression of Dock2 |
| GO:0032090 Pyrin domain binding | IPI PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: ASC PYD binds the pyrin domains of sensor proteins such as NLRP3. Reason: Informative molecular function central to ASC's adaptor role: ASC's PYD engages sensor PYDs (NLRP3) to nucleate the speck (PMID:15030775; PMID:27432880). Supporting Evidence: PMID:27432880 We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. |
| GO:0032090 Pyrin domain binding | IPI PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: ASC PYD self-associates and binds sensor PYDs. Reason: ASC PYD-PYD interactions (self-association and sensor binding) underpin filament nucleation (PMID:27432880; PMID:15641782). Supporting Evidence: PMID:27432880 We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. PMID:15641782 the PYD of ASC was shown to form cytoplasmic filaments through self-association |
| GO:0032688 negative regulation of interferon-beta production | IMP PMID:19158675 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activa... | KEEP AS NON CORE | Summary: ASC-deficient macrophages produce more IFN-beta after cytosolic DNA, so ASC restrains IFN-beta production. Reason: Experimental: loss of ASC raises IFN-beta (PMID:19158675), indicating ASC negatively regulates IFN-beta, likely by diverting responding cells to pyroptosis. A secondary, non-core consequence of inflammasome activity. Supporting Evidence: PMID:19158675 We speculate, that the increased cytokine production in ASC-deficient cells relates to their resistance to poly(dA-dT) induced cell death. |
| GO:0032722 positive regulation of chemokine production | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (mouse) positive regulation of chemokine production. Reason: ASC promotes chemokine expression via a caspase-1/IL-1b-independent MAPK/DUSP10 route (PMID:21487011); secondary role. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0032722 positive regulation of chemokine production | IMP PMID:21487011 The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activat... | KEEP AS NON CORE | Summary: ASC promotes chemokine production via DUSP10/MAPK, independent of caspase-1. Reason: Experimental (PMID:21487011): ASC suppresses DUSP10 to raise MAPK-driven chemokine output independently of the inflammasome. Secondary, non-core. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. PMID:21487011 Chemokine induction, DUSP function, and MAPK phosphorylation were independent of caspase-1 and IL-1 |
| GO:0032729 positive regulation of type II interferon production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic (mouse) positive regulation of IFN-gamma production. Reason: IFN-gamma relates to ASC's secondary adaptive-immunity/T-cell effects, partly confounded by the Dock2 mutation; non-core and transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0032729 positive regulation of type II interferon production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS (mouse) positive regulation of IFN-gamma production. Reason: Same secondary T-cell-associated role transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: ASC is required for NALP3-inflammasome IL-1b processing/secretion. Reason: Core output: ASC assembles the inflammasome that matures IL-1b (PMID:15030775). 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:0032731 positive regulation of interleukin-1 beta production | IDA PMID:16037825 Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, v... | ACCEPT | Summary: ASC oligomerization drives caspase-1 activation and IL-1b processing. Reason: Core output (PMID:16037825). Supporting Evidence: PMID:16037825 pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, 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: ASC filament assembly activates caspase-1 for IL-1b maturation. Reason: Core output; ASC nucleates caspase-1 filaments for proximity-induced activation (PMID:24630722). Supporting Evidence: PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation. |
| GO:0032731 positive regulation of interleukin-1 beta production | IDA PMID:7642516 Cleavage of poly(ADP-ribose) polymerase by interleukin-1 bet... | ACCEPT | Summary: Caspase-1/ICE processes pro-IL-1b downstream of the ASC inflammasome. Reason: ASC-activated caspase-1 (ICE) matures IL-1b (PMID:7642516 characterizes ICE pro-IL-1b processing). Core output. Supporting Evidence: PMID:7642516 PARP cleavage, however, requires a 50-100-fold higher ICE concentration than does processing of the interleukin-1 beta precursor at an equivalent substrate concentration. |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic positive regulation of IL-1b production. Reason: Consistent with the core IL-1b-maturation output. |
| GO:0032731 positive regulation of interleukin-1 beta production | IMP PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | ACCEPT | Summary: Dectin-1 drives ASC-dependent IL-1b maturation via a noncanonical caspase-8 inflammasome. Reason: Experimental (PMID:22267217): ASC is recruited into the dectin-1/caspase-8 scaffold to process IL-1b. Supports the core IL-1b-production role. Supporting Evidence: PMID:22267217 the recruitment of MALT1-caspase-8 and ASC into this scaffold was crucial for processing of pro-IL-1 |
| GO:0032731 positive regulation of interleukin-1 beta production | NAS PMID:21918512 The NLRC4 inflammasome receptors for bacterial flagellin and... | ACCEPT | Summary: Positive regulation of IL-1b production (NAS). Reason: Consistent with the core IL-1b-maturation output. |
| GO:0032733 positive regulation of interleukin-10 production | IMP PMID:16982856 Cutting edge: ASC mediates the induction of multiple cytokin... | KEEP AS NON CORE | Summary: ASC is required for P. gingivalis-induced IL-10 (partly caspase-1-independent). Reason: Experimental (PMID:16982856): ASC required for IL-10 induction via caspase-1-independent/NF-kB routes. Secondary cytokine-induction role. Supporting Evidence: PMID:16982856 Induction of IL-6, IL-8, IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic positive regulation of IL-6 production. Reason: ASC promotes IL-6 via caspase-1-independent routes (PMID:16982856); secondary. Supporting Evidence: PMID:16982856 Induction of IL-6, IL-8, IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. |
| GO:0032755 positive regulation of interleukin-6 production | IMP PMID:16982856 Cutting edge: ASC mediates the induction of multiple cytokin... | KEEP AS NON CORE | Summary: ASC required for P. gingivalis-induced IL-6. Reason: Experimental (PMID:16982856); secondary, caspase-1-independent cytokine induction. Supporting Evidence: PMID:16982856 Induction of IL-6, IL-8, IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. |
| GO:0032755 positive regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS (mouse) positive regulation of IL-6 production. Reason: Secondary cytokine-induction role transferred from mouse. |
| GO:0032757 positive regulation of interleukin-8 production | IMP PMID:16982856 Cutting edge: ASC mediates the induction of multiple cytokin... | KEEP AS NON CORE | Summary: ASC required for P. gingivalis-induced IL-8. Reason: Experimental (PMID:16982856); secondary caspase-1-independent cytokine induction. Supporting Evidence: PMID:16982856 Induction of IL-6, IL-8, IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. |
| GO:0032760 positive regulation of tumor necrosis factor production | IMP PMID:16982856 Cutting edge: ASC mediates the induction of multiple cytokin... | KEEP AS NON CORE | Summary: ASC required for P. gingivalis-induced TNF. Reason: Experimental (PMID:16982856); secondary, caspase-1-independent. Supporting Evidence: PMID:16982856 Induction of IL-6, IL-8, IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. |
| GO:0032760 positive regulation of tumor necrosis factor production | IMP PMID:21487011 The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activat... | KEEP AS NON CORE | Summary: ASC promotes TNF production via the MAPK/DUSP10 route. Reason: Experimental (PMID:21487011); caspase-1-independent MAPK-driven cytokine output. Secondary. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0032991 protein-containing complex | IDA PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | MARK AS OVER ANNOTATED | Summary: ASC is a component of inflammasome protein complexes. Reason: True but uninformative: the specific complexes ASC belongs to (canonical/NLRP3/NLRP1/AIM2/NLRP6 inflammasomes) are annotated precisely elsewhere, so the generic term adds nothing. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic generic protein-containing complex. Reason: Generic; superseded by the specific inflammasome-complex annotations. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IDA PMID:12656673 The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-... | KEEP AS NON CORE | Summary: ASC modulates TNF/NF-kB signaling (POP1 study). Reason: Experimental role in TNF signalling modulation (PMID:12656673); secondary. Supporting Evidence: PMID:12656673 POP1/ASC2 associates with ASC via PAAD-PAAD interactions and modulates NF-kappa B and pro-caspase-1 regulation by this adapter protein |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | MARK AS OVER ANNOTATED | Summary: Secretory granule lumen via Reactome neutrophil degranulation. Reason: Reactome degranulation-pathway membership, not a characteristic ASC localization. |
| GO:0035578 azurophil granule lumen | TAS Reactome:R-HSA-6798751 | MARK AS OVER ANNOTATED | Summary: Azurophil granule lumen via Reactome neutrophil degranulation. Reason: Reactome degranulation-pathway membership, not a characteristic ASC localization. |
| GO:0038187 pattern recognition receptor activity | IBA GO_REF:0000033 | REMOVE | Summary: Phylogenetic assignment of pattern-recognition-receptor activity. Reason: ASC is the inflammasome adaptor, not a sensor: it has only PYD and CARD death-fold domains and lacks the LRR/NACHT/HIN ligand-recognition modules that confer PRR activity. The function arose in the NLR/ALR sensors of this PANTHER family (e.g. NLRP1), not in ASC, so the IBA is mis-propagated to the adaptor. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN005327833 SUPPORTS SOURCE BUT NOT TARGET Node-level PRR activity reflects the NLR/ALR sensor members; ASC is the adaptor and does not itself recognize a molecular pattern. Supporting Evidence: PMID:24630722 The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain (PYD) interactions between sensors and ASC and through caspase activation and recruitment domain (CARD) interactions between ASC and caspase-1. |
| GO:0042104 positive regulation of activated T cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) positive regulation of activated T-cell proliferation. Reason: Part of the ASC T-cell/adaptive-immunity phenotype confounded by the Dock2 passenger mutation (PMID:22905357). Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0042104 positive regulation of activated T cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) positive regulation of activated T-cell proliferation. Reason: Same Dock2-confounded T-cell phenotype transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0042742 defense response to bacterium | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic defense response to bacterium. Reason: ASC inflammasomes contribute to antibacterial defense; broad and electronically assigned, non-core. |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC links p53/genotoxic stress to Bax-dependent mitochondrial apoptosis. Reason: Experimental overexpression/knockdown evidence (PMID:14730312) for a p53-Bax apoptotic role; secondary to the inflammasome function. Supporting Evidence: PMID:14730312 ASC is required to translocate Bax to the mitochondria |
| GO:0042802 identical protein binding | IDA PMID:34341353 SARS-CoV-2 N protein promotes NLRP3 inflammasome activation ... | ACCEPT | Summary: ASC self-associates/oligomerizes (SARS-CoV-2 N study, IDA). Reason: Informative MF: ASC homo-oligomerization is central to speck formation; N protein promotes ASC oligomerization (PMID:34341353). Supporting Evidence: PMID:34341353 SARS-CoV-2 N protein specifically promoted ASC oligomerization mediated by NLRP3 |
| GO:0042802 identical protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic identical protein binding. Reason: Consistent with ASC self-association/homo-oligomerization. |
| GO:0042802 identical protein binding | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: ASC self-association drives filament/speck assembly. Reason: ASC PYD and CARD both polymerize via homotypic self-interaction (PMID:24630722). Supporting Evidence: PMID:24630722 Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. |
| GO:0042802 identical protein binding | IPI PMID:25006247 Identification of multifaceted binding modes for pyrin and A... | ACCEPT | Summary: ASC PYD self-association (NMR/docking). Reason: ASC PYD self-associates (PMID:25006247). Supporting Evidence: PMID:25006247 both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: ASC self-interaction (interactome). Reason: Consistent with ASC homo-oligomerization. Supporting Evidence: PMID:24630722 Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. |
| GO:0042802 identical protein binding | IPI PMID:29408806 Loss-of-function CARD8 mutation causes NLRP3 inflammasome ac... | ACCEPT | Summary: ASC self-association in the CARD8/NLRP3 study. Reason: Consistent with ASC homo-oligomerization underlying speck assembly. Supporting Evidence: PMID:27432880 We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. |
| GO:0042803 protein homodimerization activity | IDA PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: ASC forms homodimers/oligomers in the inflammasome. Reason: Informative MF: ASC dimerization/oligomerization is the basis of the pyroptosome/speck (PMID:17599095; PMID:15030775). Supporting Evidence: PMID:17599095 The pyroptosome is largely composed of oligomerized ASC dimers. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic regulation of apoptotic process. Reason: ASC modulates apoptosis in several systems; broad and non-core. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic (rat) neuronal cell body. Reason: Ortholog-based localization with no specific functional characterization in human; non-core. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:12646168 ASC is an activating adaptor for NF-kappa B and caspase-8-de... | KEEP AS NON CORE | Summary: ASC oligomerization induces caspase-8-dependent apoptosis. Reason: Experimental (PMID:12646168), largely overexpression-based; a secondary pro-apoptotic activity. Supporting Evidence: PMID:12646168 co-expression of ASC with Ipaf or oligomerization of ASC induces both apoptosis and NF-kappa B activation |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:12656673 The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-... | KEEP AS NON CORE | Summary: ASC can activate NF-kB in reconstitution assays. Reason: ASC's effect on NF-kB is context-dependent (activating or inhibiting); reported activation (PMID:12656673) is a secondary, non-core role. Supporting Evidence: PMID:12656673 POP1/ASC2 associates with ASC via PAAD-PAAD interactions and modulates NF-kappa B and pro-caspase-1 regulation by this adapter protein |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC suppresses IKK activation to inhibit NF-kB under proinflammatory stimuli. Reason: Experimental (PMID:12486103): raising ASC suppresses IKK/NF-kB. Part of ASC's dual, context-dependent NF-kB modulation; secondary. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic negative regulation of canonical NF-kB. Reason: Consistent with the experimental IKK-suppression role; secondary. Supporting Evidence: PMID:12486103 ASC modulates diverse NF-kappaB induction pathways by acting upon the IKK complex |
| GO:0044325 transmembrane transporter binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transmembrane transporter binding (IEA), transferred from rat Pycard, from a study of pannexin 1 association with inflammasome proteins (PMID:19416975). Reason: The row is transferred from rat Pycard, where it rests on a physical-interaction annotation from the study showing that the pannexin 1 channel associates with inflammasome proteins in neurons and astrocytes (PMID:19416975), so a real co-association lies behind it. Recovery of ASC with a channel in an inflammasome-containing complex does not establish binding of transporters as a function of ASC, whose role is that of the inflammasome adaptor. The term over-reads the interaction and is marked as an over-annotation, like the protease binding row from the same source, rather than removed. |
| GO:0044351 macropinocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) macropinocytosis. Reason: Part of the Dock2/Rac/actin-dependent DC antigen-uptake phenotype (PMID:21892172) later attributed to a Dock2 passenger mutation (PMID:22905357). Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0044351 macropinocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) macropinocytosis. Reason: Same Dock2-confounded uptake phenotype transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0044546 NLRP3 inflammasome complex assembly | IDA PMID:27432880 ASC Pyrin Domain Self-associates and Binds NLRP3 Protein Usi... | ACCEPT | Summary: ASC binds NLRP3 PYD and self-associates to assemble the NLRP3 inflammasome. Reason: Core: ASC PYD-PYD interactions with NLRP3 nucleate inflammasome assembly (PMID:27432880). Supporting Evidence: PMID:27432880 We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. |
| GO:0045087 innate immune response | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic (InterPro) innate immune response. Reason: ASC is a core innate-immune inflammasome adaptor. |
| GO:0046330 positive regulation of JNK cascade | IMP PMID:21487011 The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activat... | KEEP AS NON CORE | Summary: ASC promotes JNK signaling via DUSP10 suppression. Reason: Experimental (PMID:21487011); caspase-1-independent MAPK-regulatory role. Secondary. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0046456 icosanoid biosynthetic process | NAS PMID:22902502 Rapid induction of inflammatory lipid mediators by the infla... | MARK AS OVER ANNOTATED | Summary: Eicosanoid-storm study (NAIP/NLRC4-driven). Reason: The cited eicosanoid response (PMID:22902502) is driven by the NAIP5/NLRC4/caspase-1 axis and is IL-1b/IL-18-independent; the paper does not establish an ASC requirement, so attributing icosanoid biosynthesis to ASC is an over-annotation. Supporting Evidence: PMID:22902502 inflammasome activation by flagellin leads to a loss of vascular fluid into the intestine and peritoneal cavity |
| GO:0046983 protein dimerization activity | IDA PMID:24531343 The PYRIN domain-only protein POP3 inhibits ALR inflammasome... | ACCEPT | Summary: ASC dimerizes (POP3 ALR-inflammasome study). Reason: Informative MF: ASC dimerization/oligomerization underpins speck assembly (PMID:24531343 context). Supporting Evidence: PMID:24531343 POP3, which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic protein dimerization activity. Reason: Consistent with ASC self-dimerization/oligomerization. |
| GO:0050727 regulation of inflammatory response | IDA PMID:21575908 IFI16 acts as a nuclear pathogen sensor to induce the inflam... | ACCEPT | Summary: ASC regulates the inflammatory response in the nuclear IFI16 inflammasome. Reason: ASC forms a functional inflammasome with IFI16 to drive the inflammatory response (PMID:21575908). Supporting Evidence: PMID:21575908 interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome |
| GO:0050729 positive regulation of inflammatory response | IDA PMID:12191486 The inflammasome: a molecular platform triggering activation... | ACCEPT | Summary: ASC is required for inflammasome-driven inflammation. Reason: Core: ASC-dependent inflammasomes drive the inflammatory response (PMID:12191486). Supporting Evidence: PMID:12191486 proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic positive regulation of inflammatory response. Reason: Consistent with the core pro-inflammatory inflammasome role. |
| 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 (NAS, NLRC4). Reason: Consistent with the core pro-inflammatory role. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| 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 (NAS, inflammasome assembly). Reason: Consistent with the core pro-inflammatory role; ASC nucleates caspase-1 activation (PMID:24630722). Supporting Evidence: PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation. |
| GO:0050729 positive regulation of inflammatory response | NAS PMID:29255148 Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflamm... | ACCEPT | Summary: Positive regulation of inflammatory response (NAS, SHP2 study). Reason: Consistent with the core pro-inflammatory role. |
| GO:0050766 positive regulation of phagocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) positive regulation of phagocytosis. Reason: Part of the Dock2/Rac/actin DC-uptake phenotype (PMID:21892172) attributed to a Dock2 passenger mutation (PMID:22905357). Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0050766 positive regulation of phagocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) positive regulation of phagocytosis. Reason: Same Dock2-confounded phenotype transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:16982856 Cutting edge: ASC mediates the induction of multiple cytokin... | KEEP AS NON CORE | Summary: ASC required for responses to Gram-negative bacteria (P. gingivalis). Reason: Experimental (PMID:16982856); ASC-dependent antibacterial cytokine responses. Non-core relative to the inflammasome mechanism itself. Supporting Evidence: PMID:16982856 we demonstrate an essential role for ASC in induction of IL-1beta by TLR2, 4, and 5 agonists, live Escherichia coli, and Pg |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:21487011 The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activat... | KEEP AS NON CORE | Summary: ASC contributes to antibacterial defense via MAPK/chemokines. Reason: Experimental (PMID:21487011); secondary antibacterial role. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0050870 positive regulation of T cell activation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic (ARBA) positive regulation of T-cell activation. Reason: T-cell-activation role is part of the Dock2-confounded adaptive-immunity phenotype (PMID:22905357). Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:0050870 positive regulation of T cell activation | IMP PMID:22732093 Central and overlapping role of Cathepsin B and inflammasome... | KEEP AS NON CORE | Summary: ASC knockdown in human DCs reduces T-cell stimulation. Reason: Human RNAi evidence (PMID:22732093) for a secondary role in T-cell activation via DC function; non-core. Supporting Evidence: PMID:22732093 RNAi mediated inhibition of the inflammasome component ASC leads to marked inhibition of the capacity of lipopolysachharide (LPS)-matured DCs to stimulate antigen-specific T cells. |
| GO:0051260 protein homooligomerization | IDA PMID:24531343 The PYRIN domain-only protein POP3 inhibits ALR inflammasome... | ACCEPT | Summary: ASC oligomerizes to form the pyroptosome/speck. Reason: Core process: ASC self-oligomerization builds the caspase-1-activating platform (PMID:24531343; PMID:17599095). Supporting Evidence: PMID:17599095 The pyroptosome is largely composed of oligomerized ASC dimers. |
| GO:0051260 protein homooligomerization | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic protein homooligomerization. Reason: Consistent with the core ASC self-oligomerization that forms the speck. |
| GO:0051607 defense response to virus | IDA PMID:21575908 IFI16 acts as a nuclear pathogen sensor to induce the inflam... | KEEP AS NON CORE | Summary: ASC forms the IFI16 nuclear inflammasome in antiviral defense. Reason: Experimental (PMID:21575908) antiviral role via IFI16; secondary relative to the generic adaptor function. Supporting Evidence: PMID:21575908 interferon gamma-inducible protein 16 (IFI16) interacts with the adaptor molecule ASC and procaspase-1 to form a functional inflammasome |
| GO:0051607 defense response to virus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic defense response to virus. Reason: ASC participates in antiviral inflammasomes (AIM2/IFI16/NLRP6); secondary. |
| GO:0051607 defense response to virus | NAS PMID:28314590 Inflammasome Activation Triggers Caspase-1-Mediated Cleavage... | KEEP AS NON CORE | Summary: ASC modulates antiviral defense by inflammasome cross-regulation of cGAS. Reason: ASC/caspase-1 cleave cGAS to dampen IFN during DNA-virus infection (PMID:28314590); a regulatory, non-core antiviral role. 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 | EXP PMID:12191486 The inflammasome: a molecular platform triggering activation... | ACCEPT | Summary: ASC is a defining component of the canonical inflammasome. Reason: Core complex: ASC is a subunit of the caspase-1-activating inflammasome (PMID:12191486). Supporting Evidence: PMID:12191486 The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. |
| GO:0061702 canonical inflammasome complex | EXP PMID:15030775 NALP3 forms an IL-1beta-processing inflammasome with increas... | ACCEPT | Summary: ASC in the NALP3 canonical inflammasome. Reason: Core complex membership (PMID:15030775). 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:0061702 canonical inflammasome complex | EXP PMID:30674671 Molecular mechanism for NLRP6 inflammasome assembly and acti... | ACCEPT | Summary: ASC in the canonical (NLRP6) inflammasome. Reason: Core complex membership; ASC is recruited to assemble the active complex (PMID:30674671). Supporting Evidence: PMID:30674671 can recruit the ASC adaptor using PYD-PYD interactions |
| GO:0061702 canonical inflammasome complex | EXP PMID:34678144 Phase separation drives RNA virus-induced activation of the ... | ACCEPT | Summary: ASC in the canonical (NLRP6) inflammasome. Reason: Core complex membership (PMID:34678144). Supporting Evidence: PMID:34678144 Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. |
| GO:0061702 canonical inflammasome complex | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic canonical inflammasome complex. Reason: Consistent with core inflammasome-complex membership. |
| GO:0061702 canonical inflammasome complex | IPI PMID:16037825 Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, v... | ACCEPT | Summary: ASC oligomerization reconstitutes the caspase-1-activating inflammasome. Reason: Core complex membership; ASC oligomerization assembles the active complex (PMID:16037825). Supporting Evidence: PMID:16037825 pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, caspase-1 activation and interleukin-1beta processing |
| GO:0061702 canonical inflammasome complex | NAS PMID:25879286 The NAIP-NLRC4 inflammasome in innate immune detection of ba... | ACCEPT | Summary: Canonical inflammasome complex (NAS, NAIP-NLRC4). Reason: Consistent with core inflammasome-complex membership. Supporting Evidence: PMID:25879286 Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: ASC inflammasomes trigger pyroptosis. Reason: Core output: ASC-dependent inflammasomes drive pyroptotic cell death (PMID:19158676). Supporting Evidence: PMID:19158676 interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1 |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:26121197 Inflammasomes: mechanism of action, role in disease, and the... | ACCEPT | Summary: Pyroptotic inflammatory response (NAS review). Reason: Consistent with the core pyroptosis output. Supporting Evidence: PMID:29196474 The inflammasome platform leads to activation of caspase-1 through proximity-induced self-cleavage |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:26611636 Gasdermin D is an executor of pyroptosis and required for in... | ACCEPT | Summary: Gasdermin-D pyroptosis downstream of ASC inflammasomes. Reason: ASC-dependent caspase-1 cleaves gasdermin D for pyroptosis (PMID:26611636). Supporting Evidence: PMID:26611636 The induction of apoptosis required NLRP3 or other inflammasome receptors and ASC |
| GO:0070269 pyroptotic inflammatory response | NAS PMID:29196474 Inflammasome activation and assembly at a glance. | ACCEPT | Summary: Pyroptotic inflammatory response (NAS review). Reason: Consistent with the core pyroptosis output. Supporting Evidence: PMID:29196474 The inflammasome platform leads to activation of caspase-1 through proximity-induced self-cleavage |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic positive regulation of ERK cascade. Reason: ASC modulates ERK via DUSP10 (PMID:21487011); secondary MAPK-regulatory role. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IMP PMID:21487011 The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activat... | KEEP AS NON CORE | Summary: ASC promotes ERK signaling via DUSP10 suppression. Reason: Experimental (PMID:21487011); caspase-1-independent MAPK regulation. Secondary. Supporting Evidence: PMID:21487011 ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. |
| GO:0070700 BMP receptor binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | MARK AS OVER ANNOTATED | Summary: BMP receptor binding from the PML interactome screen (partner BMPR2). Reason: Not a credible ASC function. This interaction is reported only from a single PML-focused proteomic interaction screen (PMID:24407287); it does not describe an informative, reproducible molecular function of ASC and reads as a high-throughput interactome artifact rather than a biologically meaningful binding activity. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC responds to LPS to modulate NF-kB signaling. Reason: Experimental (PMID:12486103): ASC modulates responses to LPS; a priming/regulatory context rather than a core ASC function. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0071347 cellular response to interleukin-1 | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC modulates responses to IL-1beta. Reason: Experimental (PMID:12486103) regulatory response to IL-1; secondary. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC modulates responses to TNF. Reason: Experimental (PMID:12486103) regulatory response to TNF; secondary. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0071901 negative regulation of protein serine/threonine kinase activity | IDA PMID:12486103 The PAAD/PYRIN-family protein ASC is a dual regulator of a c... | KEEP AS NON CORE | Summary: ASC suppresses IKK (IkappaB kinase) activity. Reason: Experimental (PMID:12486103): ASC suppresses IKK kinase activity. A secondary regulatory activity, consistent with its negative NF-kB modulation. Supporting Evidence: PMID:12486103 Elevations in ASC protein levels or of the PAAD domain of ASC suppressed activation of IkappaB kinases in cells exposed to pro-inflammatory stimuli. |
| GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator | IMP PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC acts in p53-dependent intrinsic (Bax) apoptosis. Reason: Experimental (PMID:14730312); secondary apoptotic role. Supporting Evidence: PMID:14730312 ASC is required to translocate Bax to the mitochondria |
| GO:0072558 NLRP1 inflammasome complex | IDA PMID:12191486 The inflammasome: a molecular platform triggering activation... | ACCEPT | Summary: ASC is a component of the NLRP1 inflammasome. Reason: Core complex: ASC is part of the NALP1/NLRP1 inflammasome (PMID:12191486). Supporting Evidence: PMID:12191486 The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. |
| GO:0072558 NLRP1 inflammasome complex | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic NLRP1 inflammasome complex. Reason: Consistent with experimental NLRP1 complex membership. |
| GO:0072558 NLRP1 inflammasome complex | IPI PMID:17349957 Reconstituted NALP1 inflammasome reveals two-step mechanism ... | ACCEPT | Summary: ASC enhances caspase-1 activation by the reconstituted NLRP1 inflammasome. Reason: ASC is recruited to the NLRP1 inflammasome (PMID:17349957); membership accepted, with the caveat that ASC enhances but is not strictly required for NLRP1. Supporting Evidence: PMID:17349957 Caspase-1 activation by NALP1 does not require but is enhanced by adaptor protein ASC. |
| GO:0072559 NLRP3 inflammasome complex | IBA GO_REF:0000033 | ACCEPT | Summary: ASC is a defining subunit of the NLRP3 inflammasome. Reason: Core complex; the NLRP3 inflammasome consists of NLRP3, PYCARD and caspase-1 (IBA + experimental). 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: ASC in the NALP3 inflammasome. Reason: Core complex membership (PMID:15030775). 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: ASC in the NLRP3 inflammasome (SHP2 study). Reason: Core complex membership; ASC bridges NLRP3 to caspase-1 (PMID:29255148 context). 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:0090200 positive regulation of release of cytochrome c from mitochondria | IDA PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC promotes Bax-dependent cytochrome c release. Reason: Experimental overexpression evidence (PMID:14730312) for a mitochondrial apoptotic role; secondary. Supporting Evidence: PMID:14730312 induced cytochrome c release with a significant reduction of mitochondrial membrane potential and resulted in the activation of caspase-9, -2 and -3 |
| GO:0097169 AIM2 inflammasome complex | IDA PMID:19158676 AIM2 activates the inflammasome and cell death in response t... | ACCEPT | Summary: ASC is a component of the AIM2 inflammasome. Reason: Core complex: AIM2 recruits ASC to activate caspase-1 (PMID:19158676). Supporting Evidence: PMID:19158676 interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1 |
| GO:0097169 AIM2 inflammasome complex | IPI PMID:24630722 Unified polymerization mechanism for the assembly of ASC-dep... | ACCEPT | Summary: ASC in the AIM2 inflammasome (filament study). Reason: Core complex membership; AIM2 nucleates ASC PYD filaments (PMID:24630722). Supporting Evidence: PMID:24630722 Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. |
| GO:0097190 apoptotic signaling pathway | IMP PMID:22267217 Dectin-1 is an extracellular pathogen sensor for the inducti... | KEEP AS NON CORE | Summary: ASC in the noncanonical caspase-8 (dectin-1) apoptotic/inflammatory scaffold. Reason: Experimental (PMID:22267217): ASC recruited into a caspase-8 scaffold. A secondary apoptotic/caspase-8 role. Supporting Evidence: PMID:22267217 the recruitment of MALT1-caspase-8 and ASC into this scaffold was crucial for processing of pro-IL-1 |
| GO:0097193 intrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred intrinsic apoptotic signaling. Reason: ASC participates in apoptosis in several systems; a secondary, non-core role relative to its inflammasome function. |
| GO:0140608 cysteine-type endopeptidase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: ASC activates procaspase-1 by nucleating its CARD filament. Reason: Core MF: clustered ASC CARDs nucleate caspase-1 CARD filaments, driving proximity-induced activation (IBA + PMID:24630722). Supporting Evidence: PMID:24630722 ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation. |
| GO:0140608 cysteine-type endopeptidase activator activity | NAS PMID:12019269 PYPAF7, a novel PYRIN-containing Apaf1-like protein that reg... | ACCEPT | Summary: ASC with sensors activates caspase-1 for cytokine processing (NAS). Reason: Consistent with the core caspase-1-activator MF (PMID:12019269 shows ASC-dependent caspase-1 activation). Supporting Evidence: PMID:12019269 Co-expression of PYPAF7 and ASC results in the synergistic activation of caspase-1 and a corresponding increase in secretion of interleukin-1 beta. |
| GO:0140632 canonical inflammasome complex assembly | IEA GO_REF:0000117 | ACCEPT | Summary: ASC nucleates canonical inflammasome assembly. Reason: Core process: ASC PYD/CARD polymerization assembles the canonical inflammasome (PMID:24630722). Supporting Evidence: PMID:24630722 Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. |
| GO:0140738 NLRP6 inflammasome complex | IDA PMID:30674671 Molecular mechanism for NLRP6 inflammasome assembly and acti... | ACCEPT | Summary: ASC is a component of the NLRP6 inflammasome. Reason: Core complex: NLRP6 recruits ASC to activate caspase-1 (PMID:30674671). Supporting Evidence: PMID:30674671 can recruit the ASC adaptor using PYD-PYD interactions |
| GO:0140738 NLRP6 inflammasome complex | IDA PMID:34678144 Phase separation drives RNA virus-induced activation of the ... | ACCEPT | Summary: ASC in the NLRP6 inflammasome (phase-separation study). Reason: Core complex membership (PMID:34678144). Supporting Evidence: PMID:34678144 Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. |
| GO:0140738 NLRP6 inflammasome complex | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic NLRP6 inflammasome complex. Reason: Consistent with experimental NLRP6 complex membership. |
| GO:1900016 negative regulation of cytokine production involved in inflammatory response | IMP PMID:24531343 The PYRIN domain-only protein POP3 inhibits ALR inflammasome... | KEEP AS NON CORE | Summary: POP3 competes with ASC to limit ALR-inflammasome cytokine output. Reason: Experimental context (PMID:24531343) in which ASC-dependent ALR inflammasomes drive cytokines that POP3 restrains; the negative-regulation framing is indirect for ASC. Non-core. Supporting Evidence: PMID:24531343 POP3, which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IPI PMID:15817483 PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedbac... | KEEP AS NON CORE | Summary: PYPAF3/ASC modulation of NF-kB signaling. Reason: PYPAF3 is a feedback inhibitor of caspase-1-dependent IL-1b secretion acting with ASC (PMID:15817483); the non-canonical NF-kB claim is weakly supported and secondary for ASC. Supporting Evidence: PMID:15817483 PYPAF3 is the second member that inhibits caspase-1-dependent interleukin-1beta secretion |
| GO:2000406 positive regulation of T cell migration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic (mouse) positive regulation of T-cell migration. Reason: Lymphocyte-migration role traces to the Dock2/Rac/actin phenotype (PMID:21892172) attributed to a Dock2 passenger mutation (PMID:22905357). Over-annotation. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:2000406 positive regulation of T cell migration | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS (mouse) positive regulation of T-cell migration. Reason: Same Dock2-confounded migration phenotype transferred from mouse. Supporting Evidence: PMID:22905357 Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IDA PMID:16964285 Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis... | KEEP AS NON CORE | Summary: ASC drives caspase-8-dependent (type II, Bid) apoptosis. Reason: Experimental (PMID:16964285): ASC-mediated apoptosis requires caspase-8 and Bid in type II cells. Secondary apoptotic role. Supporting Evidence: PMID:16964285 Bid was cleaved upon ASC activation, and suppression of endogenous Bid expression using small-interfering RNAs in type-II cells reduced the ASC-mediated apoptosis. |
| GO:2001242 regulation of intrinsic apoptotic signaling pathway | IDA PMID:14730312 ASC is a Bax adaptor and regulates the p53-Bax mitochondrial... | KEEP AS NON CORE | Summary: ASC regulates the p53-Bax intrinsic apoptotic pathway. Reason: Experimental (PMID:14730312); secondary apoptotic-regulatory role. Supporting Evidence: PMID:14730312 ASC is required to translocate Bax to the mitochondria |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which of ASC's reported inflammasome-independent activities (NF-kB modulation via IKK, MAPK/DUSP10-driven chemokine output, caspase-8/Bax apoptosis) occur at endogenous ASC levels in primary human cells, as opposed to overexpression systems?
Q: Are any of the dendritic-cell, antigen-presentation, actin-polymerization, phagocytosis and T-cell annotations genuine ASC functions in human cells, given that the mouse phenotypes were attributed to a Dock2 passenger mutation present in only some ASC-knockout lines (PMID:22905357)?
Experiment: Reconstitute endogenous-level ASC in ASC-null human macrophages with separation-of-function PYD and CARD point mutants and measure speck formation, caspase-1 activation, IL-1 beta/IL-18 release and pyroptosis, to map which residues support each step of the adaptor function.
Experiment: In Dock2-wild-type and Dock2-mutant isogenic ASC-knockout mouse lines (and CRISPR ASC-knockout human DCs), directly test antigen uptake, macropinocytosis, actin polymerization and T-cell priming to resolve which adaptive-immunity phenotypes are ASC-intrinsic versus Dock2-confounded.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)